Compositions of polymers covalently attached to metal-grafted calixarenes bound to a solid support, and methods of making them

Abstract

The invention provides compositions of polymers covalently attached to polymerizable substituents on metal -grafted calixarenes that are themselves covalently bound through metal atoms to a. porous, high surface-area solid support, which support is an inorganic oxide. The polymers form a network helping stabilize the metal-grafted calixarenes on the solid support even under harsh continuous flow conditions.

Description

PATENT Attorney Docket No. UCB002WOU1 / BK2024-003-2 PCT COMPOSITIONS OF POLYMERS COVALENTLY ATTACHED TO METAL- GRAFTED CALIXARENES BOUND TO A SOLID SUPPORT, AND METHODS OF MAKING THEM CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to, and the benefit of, U.S. Provisional Patent Application No. 63 / 519,770, filed August 15, 2023, the contents of which are hereby incorporated by reference. STATEMENT OF FEDERAL FUNDING

[0002] This invention was made with government support under DE-FG02-05ER15696, awarded by the Department of Energy. The government has certain rights in the invention. BACKGROUND OF THE INVENTION

[0003] Catalysts perform critical roles in many commercial processes. Many commercial processes in areas such as energy production can use what are known as “heterogeneous” catalysts. Heterogeneous catalysts are in a different phase from that of the reactants with which the catalyst reacts, and typically involve the use of a solid catalyst and fluid (gas or liquid) phase reactants / products. The use of heterogenous catalysts typically enables faster, large-scale production because there is no need to separate the catalyst from the reactant / products in the fluid phase, so long as there is no leaching of the catalyst from the solid phase to the fluid phase, which can be particularly problematic in the case of liquid phase reactants / products..

[0004] In contrast, “homogeneous catalysts” are catalysts which are in the same phase as the reactants, and typically relates to catalysts which are in solution with the reactants. As homogeneous catalysts are in the same solution as the reactants, they will tend to elute with the products of the catalytic reaction. To continue producing more product, more catalyst must be added, or the catalyst in the solution must be recovered from the reactants for reuse.The recovery of homogeneous catalysts adds time and cost to the production of the desired product or products.

[0005] Attempts have been made to improve the resistance of heterogeneous catalysts to leaching by supporting molecular catalysts for liquid-phase reactions in a bulk crosslinked polymer. Such immobilization can enable molecular catalyst recovery via simple filtration, but it comes with the drawback that many sites are trapped in solvent-inaccessible domains of the bulk crosslinked polymer. These sites exist in regions that do not swell enough in the presence of a reaction solvent, and remain inaccessible for catalysis. It would be desirable to be able to form a thin porous surface polymer overlayer on a high surface area support, such as silica. Unfortunately, such overlayers do not have a robust attachment of the polymer to the surface of the substrate, making the polymer susceptible to eventually being washed off the substrate under flow conditions such as those used for commercial production of pharmaceuticals.

[0006] As described by Gutsche and Bauer, J Amer Chem Soc, 1985, 107(21):6052- 6059, calixarenes “are [1n]metacyclophanes” that “can be obtained in ring sizes from 4 to 8 aromatic residues by base-induced condensation of certain para-substituted phenols and formaldehyde.” The number of aromatic residues in a calixarene can be designated by including the number of the residues in brackets within the word between the “calix” and the “arene.” Thus, the term “calix[4]arenes” designates a calixarene with four aromatic residues, the term “calix[6]arenes” designates a calixarene with six aromatic residues, and the term “calix[8]arenes” designates a calixarene with eight aromatic residues. Considerable information about calixarenes is known in the art and set forth in texts such as "CALIXARENES: AN INTRODUCTION" by C. David Gutsche, Monographs in Supramolecular Chemistry, Vol.10 (J. Fraser Stoddart, ed.; Royal Society of Chemistry, 2nd Ed.2008); "CALIXARENES REVISITED," also by C. David Gutsche (1998), and “CALIXARENES AND BEYOND,” Placido Nero et al., eds., Springer, 2016.

[0007] In 2002, methods of immobilizing calixarenes on solid supports were developed. See, U.S. Patent No. 6,951,690 B2. In 2015, tetrameric Ti(IV)-calix[4]arene complexes were synthesized and grafted to a hyroxylated SiO2 inorganic support. See, Winner, et al., Top Catal, 2015, 58:441-450; DOI 10.1007 / s11244-015-0385-x.

[0008] In 2016, it was reported that a cross-linked surface polymer layer using vinyl substituents on surface-grafted groups resulted in sites covered (blanketed) by the polymer.The polymer was not robustly anchored to the surface-grafted groups. See, Guo, et al., ACS Catalysis, 2016, 6(11):7760 – 7768. DOI:10.1021 / acscatal.6b01998. That is to say, in spite of efforts to covalently attach the polymer to the grafted calixarene, there was no such covalent attachment. Instead, the surface polymer was non-covalently attached to the solid surface (i.e. there were no covalent bonds linking the polymer to the solid surface); however, this polymer blanket was still able to confer some additional stability to grafted calixarenes against leaching.

[0009] It would be desirable to have compositions and methods that hold homogeneous catalysts to a substrate, such as an oxide surface, in a thin layer allowing reactants in a solution access to the catalytic sites, while securing the catalyst to the substrate under flow conditions. Surprisingly, the present invention fulfills these and other needs. BRIEF SUMMARY OF INVENTION

[0010] In a first group of embodiments, the invention provides compositions comprising a first calixarene having a lower rim and an upper rim, which first calixarene is substituted with a first polymerizable substituent, which first calixarene is (a) covalently bound through said polymerizable substituent to a first crosslinked polymer strand 4 to 200 monomers in length, and (b) covalently bound through a metal atom to a porous oxide surface. In some embodiments, the metal atom through which said first calixarene is covalently bound to said porous oxide surface is titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or iron. In some embodiments, the metal atom through which said first calixarene is covalently bound to said porous oxide surface is aluminum, titanium, or silicon. In some embodiments, the metal atom through which said first calixarene is covalently bound to said porous oxide surface is aluminum or titanium. In some embodiments, the porous oxide surface is silica, alumina, magnesium oxide, zirconia, aluminosilicate, or titania. In some embodiments, the porous oxide surface is silica. In some embodiments, the porous oxide surface is silica that has been heated to 800 ℃. In some embodiments, the first calixarene has a metal atom or a metal complex substituted on said lower rim or on said upper rim. In some embodiments, the metal atom is substituted on said lower rim of said first calixarene and said metal atom is a titanium, aluminum, zirconium, hafnium, boron, gallium, or germanium atom. In some embodiments, the metal complex is substituted on said upper rim of said first calixarene and said metal atom is a titanium, aluminum, zirconium, hafnium, boron, gallium,or germanium atom. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate, or a crosslinking variant of one of these. In some embodiments, the composition further comprises a second calixarene having a lower rim and an upper rim, which second calixarene is substituted with a second polymerizable substituent, and which second calixarene is covalently bound through a metal atom to a porous oxide surface. In some embodiments, the first crosslinked polymer strand of 4 to 200 monomers in length on said first calixarene is attached to said second polymerizable substituent on said a second calixarene covalently bound through a metal atom to said porous oxide surface. In some embodiments, the first crosslinked polymer strand is 4 to 100 monomers in length. In some embodiments, the first crosslinked polymer strand is 4 to 50 monomers in length. In some embodiments, the first crosslinked polymer strand is 8 to 25 monomers in length. In some embodiments, the first crosslinked polymer strand is 8 to 12 monomers in length. In some embodiments, the first polymer strand covalently attached to the first calixarene is 4 to 100 monomers in length is also covalently attached to a second crosslinked polymer strand 4 to 100 monomers in length, which second crosslinked polymer strand is in turn also covalently attached to a polymerizable substituent on a lower rim of a second calixarene covalently bound through a metal atom to said porous oxide surface. In some embodiments, the second polymerizable substituent of said second calixarene has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate, or a crosslinking variant of one of these. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate and said functionality of said styrene, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate is covalently bound to a first polymer strand of 4 to 200 monomers in length covalently attached to a second polymerizable substituent, which second polymerizable substituent is covalently attached to a second calixarene covalently bound through a metal atom to said porous oxide surface. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate and wherein said functionality is covalently bound to a first crosslinked polymer strand of 4 to 200 monomers in length covalently attached to a second polymerizable substituent, which secondpolymerizable substituent is covalently attached to a second calixarene covalently bound through a metal atom to said porous oxide surface. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene and said styrenic functionality is covalently attached to a crosslinking polymer strand composed of monomers of, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, styrene, or methacrylate, or of monomers of two or more of these, provided that, if said crosslinking polymer strand also comprises a plurality of crosslinking monomers. In some embodiments, the first calixarene is material 4 of Scheme 1. In some embodiments, the material 4 of Scheme 1 is covalently attached at said first styrenic moiety to a first crosslinked polymer of 4 to 200 monomers in length covalently attached to a second stryrenic moiety, which second stryrenic moiety is substituted on second calixarene covalently bound through a metal atom to a porous oxide surface. In some embodiments, the composition is material E of Scheme 6. In some embodiments, the composition is material 4-6 of Scheme 4. In some embodiments, the composition is material 11 of Scheme 3. In some embodiments, the first calixarene is a calix[4]arene. In some embodiments, the first calixarene is a calix[6]arene. In some embodiments, the first calixarene is a calix[8]arene.

[0011] In another group of embodiments, the invention provides compositions comprising a plurality of calixarenes, wherein each calixarene has a lower rim and an upper rim, each calixarene is (a) covalently bound through a metal atom to a porous oxide surface, (b) substituted with at least one polymerizable substituent, and (c) covalently bound through said at least one polymerizable substituent to a polymer strand 4 to 200 monomers in length which is also covalently bound to said at least one polymerizable substituent of a second calixarene in said plurality of calixarenes. In some embodiments, the metal atom through which each calixarene of said plurality of calixarenes is covalently bound to said porous oxide surface is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or iron atom. In some embodiments, the metal atom through which each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is a aluminum, titanium, or silicon atom. In some embodiments, the metal atom through which said each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is aluminum or titanium. In some embodiments, the metal atom through which saideach calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is titanium. In some embodiments, the porous oxide surface to which said plurality of calixarenes is covalently bound is silica, alumina, magnesium oxide, zirconia, aluminosilicate, or titania. In some embodiments, the porous oxide surface to which said plurality of calixarenes is covalently bound is silica. In some embodiments, the porous oxide surface to which said plurality of calixarenes is covalently bound is silica that has been heated to 800 ℃. In some embodiments, each calixarene of said plurality of calixarenes has a metal atom or a complex containing a metal atom substituted on said lower rim or on said upper rim. In some embodiments, the metal atom or said metal complex is substituted on said lower rim of said first calixarene is a metal atom and said metal atom is a titanium, aluminum, zirconium, hafnium, boron, gallium, or germanium atom. In some embodiments, the metal atom or said complex containing a metal atom is substituted on said lower rim of said first calixarene is a complex containing a metal atom and said metal atom is a titanium, aluminum, zirconium, hafnium, boron, gallium, or germanium atom. In some embodiments, the metal atom through which each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is silicon. In some embodiments, the metal atom through which each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is silicon. In some embodiments, each calixarene of said plurality of calixarenes has a titanium atom or a complex containing a titanium atom substituted on said lower rim or on said upper rim and said metal atom through which each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is silicon. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate, or a crosslinking variant of one of these. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene. In some embodiments, the plurality of calixarenes is of material 12a or 12b of Scheme 3. In some embodiments, the plurality of calixarenes is of material E of Scheme 6. In some embodiments, the plurality of calixarenes is of material 4-6 of Scheme 4. In some embodiments, the plurality of calixarenes are calix[4]arenes. In some embodiments, the plurality of calixarenes are calix[6]arenes. In some embodiments, the plurality of calixarenes are calix[8]arenes. In some embodiments, the crosslinking polymer strand is composed of divinyl benzene monomers. In some embodiments, the crosslinking polymer strand is composed of monomers of 1,2-diisopropylbenzene, 1,3- diisopropylbenzene, 1,4- diisopropylbenzene, or a combination of any of two or all three of these.

[0012] In another group of embodiments, the invention provides methods for stabilizing a population of calixarenes, each covalently bound through a metal atom to a porous oxide surface, on said porous oxide surface, each calixarene having a lower rim and an upper rim, said method comprising: (a) providing a population of calixarenes, each having a hydroxyl group disposed on at least four carbon atoms on said lower rim of said calixarene, (b) covalently attaching a polymerizable substituent to a first hydroxyl group on a first carbon atom on said lower rim of each calixarene of said population, (c) covalently attaching to said porous oxide surface through a metal atom each calixarene of said population of calixarenes, and, (d) covalently attaching to said polymerizable substituent of each calixarene of said population of calixarenes a polymer strand of 4 to 200 in length, which polymer strand is also covalently connected to a polymerizable substituent of a different calixarene of said population of calixarenes or to another polymer strand, thereby stabilizing said population of calixarenes on said porous oxide surface. In some embodiments, the polymerizable substituent of step b has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate, or a crosslinking variant of one of these. In some embodiments, the polymerizable substituent of step b has a functionality consisting of styrene. In some embodiments, the metal atom through which each calixarene of said population of calixarenes is covalently bound to said porous oxide surface is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or iron atom. In some embodiments, the metal atom through which each calixarene of said population of calixarenes is covalently bound to said porous oxide surface is a silicon, titanium, or aluminum, atom. In some embodiments, the upper rim or said lower rim of each of said population of calixarenes is substituted with a metal atom or a complex containing a metal atom. In some embodiments, the metal atom substituted on said upper rim or said lower rim of each calixarene of said population of calixarenes is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or an iron atom. In some embodiments, the metal atom of said complex containing a metal atom substituted on said upper rim or said lower rim of each calixarene of said population of calixarenes is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or an iron atom. In some embodiments, the calixarenes are calix[4]arenes. In someembodiments, the calixarenes are calix[6]arenes. In some embodiments, the calixarenes are calix[8]arenes.

[0013] In another group of embodiments, the invention provides methods for stabilizing a population of calixarenes, each covalently bound through a metal atom to a porous oxide surface, on said porous oxide surface, each calixarene having a lower rim and an upper rim, said method comprising: (a) providing a population of calixarenes, each having a hydroxyl group disposed on at least four carbon atoms on said lower rim of said calixarene, (b) covalently attaching to said porous oxide surface through a metal atom each calixarene of said population of calixarenes,(c) covalently attaching a polymerizable substituent to a first hydroxyl group on a first carbon atom on said lower rim of each calixarene of said population, and, (d) covalently attaching to said polymerizable substituent of each calixarene of said population of calixarenes a crosslinking polymer strand 4 to 200 monomers in length, and also covalently attaching said polymer strand to a polymerizable substituent of a different calixarene of said population of calixarenes or to another crosslinking polymer strand, thereby stabilizing said population of calixarenes on said porous oxide surface. In some embodiments, the polymerizable substituent of step b has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate, or a crosslinking variant of one of these. In some embodiments, the polymerizable substituent of step b has a functionality consisting of styrene. In some embodiments, the metal atom through which each calixarene of said population of calixarenes is covalently bound to said porous oxide surface is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or iron atom. In some embodiments, the metal atom through which each calixarene of said population of calixarenes is covalently bound to said porous oxide surface is a silicon, titanium, or aluminum, atom. In some embodiments, the upper rim or said lower rim of each of said population of calixarenes is substituted with a metal atom or a complex containing a metal atom. In some embodiments, the metal atom substituted on said upper rim or said lower rim of each calixarene of said population of calixarenes is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or an iron atom. In some embodiments, the metal atom of said complex containing a metal atom substituted on said upper rim or said lower rim of each calixarene of said population of calixarenes is a silicon,titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or an iron atom. In some embodiments, the calixarenes are calix[4]arenes. In some embodiments, the calixarenes are calix[6]arenes. In some embodiments, the calixarenes are calix[8]arenes.

[0014] In another group of embodiments, the invention provides methods for stabilizing a population of calixarenes, said methods comprising a method selected from: (A) steps a-d of Scheme 3, (B) steps a-d of Scheme 4, (C) steps i-iv of Scheme 5, or, (D) steps (a) through (d) of Scheme 4. In some embodiments, the population of calixarenes is covalently attached to a porous inorganic oxide surface of silica, alumina, magnesium oxide, zirconia, aluminosilicate, or titania. In some embodiments, the porous inorganic oxide surface is silica. In some embodiments, the porous inorganic oxide surface is SiO2@800. In some embodiments, the porous inorganic oxide surface is SiO2@800. In some embodiments, the method is of method A and the population of calixarenes is material 12a or material 12b of Scheme 3. In some embodiments, the method is the method of (B) and said population of calixarenes is of material 4-6. In some embodiments, the method is the method of (C) and said population of calixarenes is of material E.

[0015] In another group of embodiments, the invention provides methods of providing a plurality of calixarenes grafted to a porous oxide surface through a metal atom, wherein members of said plurality of calixarenes grafted to a porous oxide surface through a metal atom are connected to a network of covalently crosslinked polymer strands, said method comprising (a) obtaining a plurality of calixarenes substituted with a first polymerizable substituent and grafted to a porous oxide surface through a metal atom, (b) contacting said first polymerizable substituent on said plurality of calixarenes with a plurality of polymer- forming monomers, crosslinking monomers, crosslinking comonomers, or combination of two or more of these, under conditions allowing one of said polymer-forming monomers, crosslinking monomers, or combination of two or more of these to covalently attach to said first polymerizable substituent, and then to continue polymerizing said polymer-forming monomers, crosslinking monomers, crosslinking comonomers, or combination of two or more of these, until a plurality of first crosslinking polymer strands is created, each having a length of 4 to 200 monomers, which first crosslinking polymer strands have first ends bearing unattached double bonded carbons, which first ends are disposed on said first crosslinking polymer strands distal to said first polymerizable substituents, and, (c) allowing said first ends of said plurality of first crosslinking polymer strands to attach to second polymerizablesubstituents, wherein one of each second polymerizable substituents is separately covalently attached to one of a plurality of second calixarenes, thereby providing a plurality of calixarenes grafted to a porous oxide surface through a metal atom, wherein members of said plurality of calixarenes grafted to a porous oxide surface through a metal atom are covalently attached to a network of crosslinked polymer strands. In some embodiments, the metal atoms grafting said plurality of calixarenes to said porous oxide surface are titanium, aluminum, zirconium, hafnium, boron, gallium, germanium, Si(IV), or P(V) atoms. In some embodiments, the metal atoms are aluminum or titanium atoms. In some embodiments, the porous oxide surface is silica, alumina, magnesium oxide, zirconia, aluminosilicate, or titania. In some embodiments, the porous oxide surface is silica. In some embodiments, the porous oxide surface is SiO2@800. In some embodiments, the crosslinking monomer is divinyl benzene. In some embodiments, the crosslinking monomer is 1,2-diisopropylbenzene, 1,3- diisopropylbenzene, 1,4-diisopropylbenzene, or a combination of any of two or of all three of these. In some embodiments, the length of said first crosslinking polymer is 4 to 100 monomers. In some embodiments, the length of said first crosslinking polymer is 4 to 50 monomers. In some embodiments, the first crosslinking polymer is 8 to 20 monomers. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, methacrylate, or a crosslinking variant of one of these. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate and said functionality of said styrene, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate is covalently bound to a first polymer strand of 4 to 200 monomers in length having an end distal to said first calixarene. In some embodiments, the end of said first polymer strand distal to said first calixarene is covalently attached to a second polymerizable substituent, which second polymerizable substituent is covalently attached to a second calixarene. In some embodiments, the end of said first polymer strand distal to said first calixarene is covalently attached to a second polymer strand. In some embodiments, the first polymer strand distal to said first calixarene is covalently attached to a second polymer strand, which second polymer strand is covalently attached to a second polymerizable substituent covalently attached to a second calixarene covalently bound through a metal atomto said porous oxide surface. In some embodiments, the first polymerizable substituent of said first calixarene has a functionality consisting of styrene. In some embodiments, the calixarenes are calix[4]arenes. In some embodiments, the calixarenes are calix[6]arenes. In some embodiments, the calixarenes are calix[8]arenes. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Fig. 1. Fig. 1 is a graph showing the thermogravimetric analysis of material 4 of Scheme 1 before (dashed line) and after (solid line) Soxhlet extraction with isopropyl alcohol for 24 hours. X axis: Temperature, in ℃. Y axis: Percent of material lost remaining, starting from 100%, after 24 hours of Soxhlet extraction at the four temperatures tested.

[0017] Fig. 2. Fig. 2 is a graph showing the thermogravimetric analysis of material 5 of Scheme 1 before (dashed line) and after (solid line) Soxhlet extraction with isopropyl alcohol for 24 hours. X axis: Temperature, in ℃. Y axis: Percent of material lost remaining, starting from 100%, after 24 hours of Soxhlet extraction at the four temperatures tested.

[0018] Figs. 3a and 3b. Fig. 3a Fig. 3a is the13C CP / MAS NMR spectra for compound 11 as designated in Scheme 3. Fig. 3b. Fig. 3b is the13C CP / MAS NMR spectra for compound 13 as that material is described in Example 3 and shown in Fig. 6.

[0019] Figs. 4a and 4b. Fig. 4a Fig. 4a is the13C CP / MAS NMR spectra for compound 12a as designated in Scheme 3. Fig. 4b. Fig. 4b is the13C CP / MAS NMR spectra for compound 12b as designated in Scheme 3. The resonance of the calixarene styrenic substituent at 112 ppm disappears (as shown in the insets in both Figs. enlarging that portion of each spectra), confirming the covalent connection of the crosslinked polymer to the grafted calixarene site.

[0020] Fig. 5. Fig. 5 is a graph presenting the themogravimetric analysis of materials 11 (dashed line) and 13 (solid line) at a ramp rate of 5oC per minute.

[0021] Fig. 6. Fig. 6 is a schematic representation of the outcome of hot isopropanol Soxhlet extraction for 24 h of materials 11 and 14, showing retention of the Si-O-Ti bond, but cleavage of the Ti-O-C bond, resulting in material 13 and a calixarene ligand detached from the silica oxide surface.

[0022] Fig. 7. Fig. 7 is a graph of a thermogravimetric analysis of compound 12a before (dotted line) and 12a,AS after (solid line) Soxhlet extraction with isopropyl alcohol (IPA) for 24 h.

[0023] Fig. 8. Fig. 8 is a graph of a thermogravimetric analysis of 12b before (dotted line) and 12b,AS after (solid line) Soxhlet extraction with isopropyl alcohol (IPA) for 24 h.

[0024] Fig. 9. Fig. 9 is a graph showing the kinetics of MPV reduction with grafted calixarene catalysts. TON= turnover number. TOF = turnover frequency (that is, the number of reaction events per site per unit time).

[0025] Fig. 10. Fig. 10, is a schematic representation of cyclohexene epoxidation with tert- butyl hydroperoxid.

[0026] Figs. 11A-11D. Fig. 11A. Fig. 11A is a first-order rate constant plot for epoxidation of cyclohexene with tert-butyl hydroperoxide, based on conversion (the X term in the equation on the Y axis) of the oxidant, used to calculate keffvalues, represented by the slope of the lines for material 12b,AS. Fig. 11B. Fig. 11B is a first-order rate constant plot for epoxidation of cyclohexene with tert-butyl hydroperoxide, based on conversion (the X term in the equation on the Y axis) of the oxidant, used to calculate keffvalues, represented by the slope of the lines for material 12a,AS. Fig. 11C. Fig. 11C is a first-order rate constant plot for epoxidation of cyclohexene with tert-butyl hydroperoxide, based on conversion (the X term in the equation on the Y axis) of the oxidant, used to calculate keffvalues, represented by the slope of the lines for material 13. Fig. 11D. Fig. 11D is a first-order rate constant plot for epoxidation of cyclohexene with tert-butyl hydroperoxide, based on conversion (the X term in the equation on the Y axis) of the oxidant, used to calculate keffvalues, represented by the slope of the lines for material 14. Materials in Figs. 11A-11D are numbered as those materials are numbered in Examples 3-5. All Figs.: X axis: Time, in ks.

[0027] Fig. 12. Fig. 12 is a graph of a thermogravimetric analysis of materials 4-5 and 4-6, as those materials are designated in Example 6.

[0028] Fig. 13. Fig. 13 is a graph of a thermogravimetric analysis of materials 4-5 and 4- 5,AS, as those materials are numbered in Example 6.

[0029] Fig. 14. Fig. 14 is a graph of a thermogravimetric analysis of materials 4-6 and 4- 6,AS, as those materials are numbered in Example 6.

[0030] Fig. 15. Fig. 15 is a graph showing the kinetics of Ti and Al grafted calixarene catalysts, numbered as set forth in Examples 3 (materials 11, 12a, and 12b) and 6 (material 4- 6,AS). TON= turnover number. TOF = turnover frequency (that is, the number of reaction events per site per unit time).

[0031] Fig. 16. Fig. 16 is a graph showing the kinetics of Al-bearing calixarene catalysts, numbered as set forth in Examples 6 (material 4-6,AS) and 7 (materials E and G). TON= turnover number. TOF = turnover frequency (that is, the number of reaction events per site per unit time).

[0032] Fig. 17. Fig. 17 shows the1H NMR spectrum of recovered material B (as that material is designated in Example 7) in C6D6. DETAILED DESCRIPTION

[0033] Homogeneous catalysts by definition are in the same phase as the reactants. Homogeneous catalysts in solution with the reactants whose interaction they catalyze typically have to be separated and recovered from the resulting product before they can be used in another cycle. These separation and recovery steps add time and cost to the production of a given amount of the product of the catalyzed reaction. One solution to eliminating these separation and recovery steps is by attaching the homogeneous catalyst to a support. To produce the greatest amount of the desired reaction product, the homogeneous catalyst must not only be attached to the support in a manner that secures the catalyst to the support, but also keeps the catalytic sites of the catalyst accessible to the reactants.

[0034] In industrial use, reactions in a solution are typically conducted under flow conditions so that fresh reactants are continuously coming into contact with the catalyst. Thus, the catalyst is prefereably attached to the substrate robustly enough so that as much as possible of the catalyst remains attached to the substrate under the continuous flow conditions used in industrial processes. The need for robust attachment to the substrate can be in tension with keeping the catalytic sites of the catalyst accessible to the chemical reactants.

[0035] In 2002, work from the lab of the present inventors resulted in an important advance in resolving this tension: methods of immobilizing calixarenes on solid supports by covalently attaching a metal atom to a prepared porous surface and then covalently attaching the calixarene (bearing styrene) to the metal atom. See, U.S. Patent No. 6,951,690 B2 (the “’690 patent”), the contents of which are hereby incorporated by reference. Alternatively, the calixarene can be attached to a metal atom that in turn is used to covalently attach, or “graft,” the calixarene bearing the styrene to a prepared porous surface, as described in Nandi, et al., Proc Natl Acad Sci (USA), 2013, 110(7):2484-2489 (“Nandi,” also incorporated herein byreference). Calixarenes covalently attached to a substrate through a metal atom as described in either the ‘690 patent or in Nandi are sometimes referred to herein as “grafted calixarenes.”

[0036] The metal atoms covalently linking the calixarene and the substrate, and metal complexes covalently attached to the grafted calixarenes, have the property of serving as catalysts for a variety of reactions (some reactions that can be catalyzed by such metal atoms are set forth in a separate section below). Since the filing of the ‘690 patent, considerable work has been performed to improve the ability of grafted calixarenes to serve as a platform for heterogenizing homogeneous catalysts. As noted above, covalently attaching a homogeneous catalyst, such as a metal atom, into a grafted calixarene as taught in the ‘690 patent immobilizes the catalyst on the substrate along with the calixarene. But, it was found over time that, when a population of calixarenes are grafted to a substrate following the methods taught in the ‘690 patent and then are subjected to continuous flow conditions, significant amounts of the grafted calixarene (and thus of the catalyst) can detach from the substrate. This loss of catalyst reduces the production of the desired reaction product to be obtained by use of the catalyst, reduces the yield of that product per unit time and, by increasing the time required to produce a given yield of product, increases the cost of using grafted calixarenes as a platform for such catalytic reactions. References below to “homogenous catalysts” will be understood to refer to catalytic metal atoms covalently attached to a calixarene, unless otherwise stated or required by context. polymerizable substituent

[0037] Considerable work has been performed over the twenty-plus years since the work that resulted in the ‘690 patent to improve the retention to the substrate of grafted calixarenes bearing a catalyst under continuous flow of a solution without reducing the accessability of the catalytic sites to reactants in the solution. In 2015, tetrameric Ti(IV)-calix[4]arene complexes were synthesized and grafted to a hydroxylated SiO2inorganic support. See, Winner, et al., Top Catal, 2015, 58:441-450 (“Winner”); DOI:10.1007 / s11244-015-0385-x. The complexes were composed of four calixarenes, each grafted to the substrate, and each connected to the other three calixarenes through an aromatic ligand. While retention of the grafted calixarenes to the substrate was improved compared to a population of monomeric Ti(IV)-calix[4]arenes, most of the calixarenes were leached away under wash conditions intended to act as an accelerated-aging surrogate for industrial catalysis conditions (i.e., the grafted calixarenes disclosed by Winner, et al. were not stable under continuous washing with solvent).

[0038] In 2016, one of the present inventors reported the development of a surface polymerization and cross-linking approach for the stabilization of single-site catalysts on solid surfaces, which was demonstrated using grafted Ti(IV)-calixarene Lewis acids on silica. See, Guo, et al., ACS Catalysis, 2016, 6(11):7760 – 7768. DOI:10.1021 / acscatal.6b01998 (hereafter, “Guo”). Cationic polymerization was initiated by an adsorbed B(C6F5)3, with styrene as the monomer and diisopropenylbenzene as a cross-linking agent. Following polymerization, the grafted Ti(IV)-calixarene sites on silica in the presence of cross-linked polymer were shown to maintain the catalytic activity of the same material, consisting of the same site except without the presence of the cross-linked polymer. The data indicated that the polymer formed an overlayer of the calixarenes grafted to the substrate silica surface, without causing any noticeable transport restrictions. Unfortunately, the work reported in Guo did not solve the problem of increasing the stability of grafted calixarenes with homogeneous catalysts, while maintaining access to the catalysts on a porous, high surface area support.

[0039] Surprisingly, the present invention solves problems not solved in the art over the two decades since the application resulting in the ‘690 patent was filed: success in robustly securing calixarenes to a substrate while keeping metal atoms serving as homogeneous catalysts covalently attached to the calixarene accessible for catalysis. As shown in this disclosure, reaction schemes have been developed that covalently attach polymerizable substituents to grafted calixarenes and that then allow monomers or comonomers that form crosslinking polymers to form polymer strands that are long enough to connect grafted calixarenes together in a crosslinked web, but that are short enough to avoid having the polymer strand “collapse” around the metal atoms or prevent access to the catalytic site.

[0040] In the inventive compositions and methods, the crosslinking polymer strands are covalently attached to metal-grafted calixarenes on porous, high surface area supports, such as silica, and, more generally, any porous, high surface area oxide surface to which calixarenes can be grafted, as previously described in the ‘690 patent. The crosslinked polymer covalently connected to the grafted calixarenes on the substrate connects some or all of the grafted calixarene to other grafted calixarenes around them so as to form a web on the support surface. As the individual polymers strands are composed of an average of not more than 200 monomers each, the crosslinked polymer forms an ultrathin polymer layer around the grafted calixarenes. Exemplar grafted calixarenes connected to one another by covalently attached crosslinked polymer demonstrated unprecedented retention on the substrate even under 24 hours of washing with boiling solvent, while the exemplar covalently attachedpolymer layer was ultrathin, allowing reagents access to metal atom homogeneous catalysts on the grafted calixarenes. The present disclosure thus solves the problem not solved in the ‘690 patent over twenty years ago, by Winner et al. in 2015, or by Guo et al. in 2016.

[0041] The wash conditions to which exemplar grafted calixarenes attached to a cross-linked polymer were subjected are an accelerated-aging surrogate for the conditions grafted calixarenes would be expected to be subjected to under continuous flow conditions in industrial processes. The reduction in the loss of grafted calixarenes is expected to increase the yield of the product of reactions catalyzed by the catalyst per unit time. By increasing yield per unit time, the inventive metal catalytic atom-grafted calixarene-polymer compositions are expected to reduce the cost of producing the reaction products catalyzed by those metal atoms, thereby making the use of grafted calixarenes more cost-effective at commercial scale than the calixarene-attached catalysts that were available in the art prior to this disclosure.

[0042] Without wishing to be bound by theory, it is believed that the cross-linked polymers form a web connecting multiple grafted calixarenes to each other, such that, if the wash conditions create conditions that would normally break the covalent bond attaching a first calixarene to the substrate, the cross-linked polymer strands connecting grafted calixarenes to each other would require that all the bonds are broken simultaneously around the first calixarene, thereby reducing the chance that the conditions imposed will be sufficient to detach any of the calixarenes from the substrate.

[0043] In some embodiments, the inventive methods involve covalently attaching one or multiple polymerizable substituents to the calixarene, and covalently grafting the calixarene bearing the polymerizable substituent or substituents to a prepared porous support. This can be accomplished either by attaching a metal atom that in turn is used to covalently attach, or “graft,” the calixarene bearing the polymerizable substituent or substituents to a prepared porous surface by the process described in Nandi, et al., Proc Natl Acad Sci (USA), 2013, 110(7):2484-2489, or by covalently attaching the metal atom to the prepared porous surface and then covalently attaching the calixarene (bearing the polymerizable substituent or substituents) to the metal atom, as described in the ‘690 patent. For the sake of good order, it is noted that when a polymerizable substituent is covalently bound as a substituent on a molecule, the polymerizable substituent molecule no longer exists as an independent entity, but rather as a derivative of that polymerizable substituent now forming part of a larger molecule. For ease of reference, a polymerizable substituent that has been covalently boundto a calixarene is sometimes referred to herein as a “polymerizable substituent moiety.” A particular compound used as a polymerizable substituent that has been covalently bound to a calixarene will sometimes be referred to as a “moiety” of that compound. For example, if the polymerizable substituent that has been covalently bound to a calixarene is a styrene, the portion of what was a styrene, now attached to the calixarene, will sometimes be referred to as a “styrenic moiety.”

[0044] A monomer capable of forming a crosslinking polymer strand is covalently attached to the polymerizable substituent moiety, and polymerizes to other monomers or comonomers that can form a crosslinking polymer present in the reaction mixture. The monomer or comonomer units polymerize to form a polymer of a length allowing the polymer strand to crosslink to other polymer strands covalently bound to another grafted calixarene bearing a polymerizable substituent moiety. Monomers and comonomers that can serve as polymerizable substituents, as crosslinking polymers, or both, and polymerization conditions are discussed in a later section. It is understood that the polymerizable monomer or the polymer strand that attaches to a polymerizable substituent moiety (itself attached to a calixarene) does not have an “end” when it is attached to the polymerizable substituent moiety, as it is then part of a larger chemical structure. ref

[0045] Surprisingly, it was found that the grafted calixarenes bearing catalytic metal atoms can be held to the substrate using very modest amounts of polymer. In studies underlying this disclosure, thermogravimetric analysis of exemplar calixarene-polymer compositions indicated that polymer strands composed of an average of 10 monomers per grafted calixarene were sufficient to form a network holding the calixarenes to the surface to which they had been grafted with much higher rates of retention even under 24 hours of wash with boiling solvent than the retention rates provided by previous approaches.

[0046] The low amount of polymer needed to hold the calixarenes to the surface to which they have been grafted is advantageous because it avoids having so much polymer on or around the grafted calixarene that it impedes access of reactants to the metal atom through which the calixarene is grafted to the substrate and thus to any catalytically active sites on the metal atom. Similarly, polymers that precipitate out of the reaction mixture, sometimes referred to as “collapsing,” can block access to the catalytic sites.

[0047] In embodiments of the invention, the number of monomers forming the polymer crosslinked to the grafted calixarenes is 200 to as few as 4 per grafted calixarene. It isbelieved that having average polymer lengths per grafted calixarene longer than 200 would permit the polymer strands to “collapse” around the grafted calixarenes and block reactants from contacting catalytically active sites on the metal atoms attached to the calixarenes. The length of the polymer strands used in the inventive compositions therefore strike a balance between being long enough to form a network robustly holding the calixarenes in place, while being short enough to keep the .polymer strands from collapsing and blocking access to the catalysts.

[0048] For clarity, it is noted that in referring to the number of monomers making up a crosslinked polymer, the reference is to the length of the polymer strand, with the goal of forming a web linking together mulitple calixarenes grafted to the substrate, with the web held in place by the multiple points of attachment provided by the multiple grafted calixarenes connected by the crosslinked polymer. There may be dozens, scores, hundreds, or even thousands of points of attachment provided by the grafted calixarenes connected together by strands of polymer crosslinking the grafted calixarenes to one another. The multiple points of attachment confer stability to the grafted calixarenes connected through the web of polymer. It is further noted that the phrase “the number of monomers forming the polymer crosslinked to the grafted calixarenes” refers to an average number of monomers forming the polymers attached to the grafted calixarenes across the surface of the substrate. The phrase therefore does not, and is not intended to, mean that an exact number of monomers, for example, 100 monomers, makes up the polymer strand attached to each grafted calixarene.

[0049] In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 200 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 175 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 150 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 125 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 100 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 90 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinkedto the grafted calixarenes is 4 to 80 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 70 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 60 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 50 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 40 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 30 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 20 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is 4 to 10 per grafted calixarene. In some embodiments of the invention, the number of monomers making up the polymer crosslinked to the grafted calixarenes is about 10 per grafted calixarene, with “about” with regard to the number of monomers meaning ± 2. In studies underlying the present disclosure, robust stabilization of calixarenes grafted to a solid support was demonstrated with polymer strands averaging 10 monomers per grafted calixarene.

[0050] It will be appreciated that the minimum length of the polymer strand is to be long enough to span the area between two grafted calixarenes so that the polymer can crosslink to and thereby connect the two calixarenes. It is believed that, at maximum density, there is a 2 nm distance between grafted calixarenes and that 4 monomer repeat units would bridge the distance between the closely spaced grafted calixarenes. Embodiments in which the average number of monomers per grafted calixarene is less than 4 are not expected to provide a sufficient length of polymer to span the distance between two adjacent grafted calixarenes.

[0051] As used herein, the “length” of a polymer strand and the number of monomer units composing the polymer strand mean the same thing and are used interchangably. In preferred embodiments, all of the monomers added to the reaction mix to form the polymer are crosslinking monomers, as that adds more rigidity to the polymer strands. Formation of polymers from monomers or comonomers has been practiced in the art for decades, and it is expected that the person of skill is aware of the extensive knowledge in the art on polymerization and needs no or only minimal guidance to know how to select suitable monomers and to polymerize those monomers to form polymer strands connecting graftedcalixarenes together in embodiments of the present invention. Information on monomer selection and polymerization will nonetheless be discussed in a later section.

[0052] It is noted that the average length of the polymer strands attached to the grafted calixarenes can conveniently be controlled by the concentration of the monomers or of the comonomers added to the solution in which the grafted calixarenes are present and in which the practitioner wishes the monomers to covalently bind to the polymerizable substituent on the grafted calixarenes and polymerize into polymer strands (some of the crosslinking monomers will also polymerize into strands linked to other polymer strands, which themselves are attached to polymerizable substituents on the grafted calixarenes. The amount of monomer added relative to the grafted calixarenes will vary depending on the surface area to which the calixarenes have been grafted and the density at which they have been grafted, as well as by the yield of polymerization of the monomers. In the studies reported in the Examples, the yield of polymerization was about 30% of the monomers added under the temperature and other reaction conditions employed. Persons of skill can follow the reaction scheme and conditions set forth in the Examples to obtain grafted calixarenes of a suitable length. The conditions under which the monomers are added and polymerized to the grafted calixarene are independent of the metal atom used as the catalyst. Thus, it is expected that the reaction conditions set forth in the Examples can be used to provide stability to calixarenes bearing any metal atom suitable for grafting a calixarene to a substrate (metal atoms suitable for use in grafting calixarenes to substrates are discussed in a later section).

[0053] If the reaction conditions were changed (for example, by increasing the temperature), or if a monomer with higher reactivity is used, and a 60% polymerization of the monomers added achieved, the amount of the monomers added to achieve the same average length of the polymer strands covalently attached to the grafted calixarenes would of course be reduced by half. While there is some trial and error in determining the appropriate amounts of the monomer or comonomers to add to any particular solution in which any particular concentration of calixarenes has been grafted to the substrate and the reaction conditions to result in a selected number of monomers comprising the polymer strands attached to the grafted calixarenes, it is expected that the person of skill, given the guidance of this disclosure, can readily determine the concentrations of monomers or comonomers to add to a given concentration of grafted calixarenes and the particular reaction conditions under which they wish to polymerize the monomers or comonomers, including using free radical or anionic polymerization approaches, to achieve grafted calixarenes connected by a polymerweb with strands of a length selected by the person of skill. Such trial and error to determine reaction conditions is considered routine in the art and is within the skills of any trained polymer chemist.

[0054] It is believed that the polymer forms an ultrathin layer around the grafted calixarenes. The phrase “ultrathin layer” with respect to the polymer attached to the grafted calixarenes refers to a layer with a thickness that is 6 nm or less and preferably 5, 4, 3, 2, or 1 nm, with each successively stated figure being preferable to the one stated before it.

[0055] As persons of skill are aware, neither the thinness of a polymer layer nor the number of monomers per grafted calixarene are typically measured directly. The thickness of the polymer layer, and the amount of polymer present, are instead deduced by determining the amount of polymer present by “thermogravimetric analysis,” sometimes abbreviated as “TGA.” TGA is a well-known “quantitative analytical technique that monitors the mass of a sample from 1 mg to several g as a furnace ramps temperature to as high as 1600°C under a stable or changing gas flow.” Saadatkhah, et al., Canadian J Chem Eng, 2019, 98(1):34-43, doi.org / 10.1002 / cjce.23673. As Saadatkhah, et al. explain: “The mass drops as the sample decomposes [and] volatile compounds evaporate.” TGA and methods for performing it are reviewed in, for example, Bottom, R., “Thermogravimetric Analysis,” Chapter 3 of Gabbott, ed., PRINCIPLES AND APPLICATIONS OF THERMAL ANALYSIS, Blackwell Publishing, Oxford, UK, 2008, the entirety of which is hereby incorporated by reference.

[0056] TGA can be used to determine the amounts of materials such as grafted calixarenes and polymer present in a sample. TGA allows determining the amount of organic content as the sample is heated, and knowing the amount of calixarenes used to create grafted calixarenes on a substrate, it is easy to tell by TGA how much organic content is from the grafted calixarenes and how much is from the crosslinked polymer attached to grafted calixarenes. the network will be understood to be from the polymer. For example, by knowing the amount of calixarenes and the amount of polymer from TGA, and knowing the weight of the calixarenes and of the monomers, one can deduct the weight of the calixarenes and deduce the number of monomers present.

[0057] Using “thermogravimetric analysis” as a search term in Pubmed as of July 2024 resulted in a list of over 16,000 papers, spanning a period of over 50 years, in which thermogravimetric analyses were made of a wide range of materials. Accordingly, it is assumed that persons of skill are very familiar with how to use TGA to analyze a material ofinterest and can readily use it to determine the calixarene content and the polymer content of any particular sample of grafted calixarenes covalently attached to crosslinked polymer strands.

[0058] It is expected that the practitioner can therefore use TGA to readily determine the amount of polymer present in the sample and deduce from the amount of polymer the average number of monomers in the polymer strands. Calixarenes

[0059] Calixarenes were described by Gutsche and Bauer, J Amer Chem Soc, 1985, 107(21):6052-6059, as “ [1n]metacyclophanes” that “can be obtained in ring sizes from 4 to 8 aromatic residues by base-induced condensation of certain para-substituted phenols and formaldehyde.” Extensive information about calixarenes, their chemistry, and their properties, is available in the art, as exemplified by texts such as "CALIXARENES: AN INTRODUCTION" by C. David Gutsche, Monographs in Supramolecular Chemistry, Vol. 10 (J. Fraser Stoddart, ed.; Royal Society of Chemistry, 2nd Ed.2008)(hereafter, “Gutsche 2008”); "CALIXARENES REVISITED," also by C. David Gutsche, Monographs in Supramolecular Chemistry, Vol.1 (Royal Society of Chemistry, 1998) (hereafter, “Gutsche 1998”), and “CALIXARENES AND BEYOND,” Placido Nero et al., eds., Springer, 2016, as well as scientific articles such as Solovyov, et al., New J Chem, 2008, 32:1314- 1325; and Notestein, et al., JACS, 2007, 129(50):15585-15595, all of which are hereby incorporated by reference. While the discussion in this document emphasizes certain aspects of calixarenes relevant to the present disclosure, it is expected that persons of skill are familiar with the extensive information about calixarenes available in the art.

[0060] The number of aromatic residues in a calixarene can be designated by including the number of the aromatic residues in brackets within the word “calixarene” between the “calix” and the “arene.” Thus, the term “calix[4]arenes” designates a calixarene with four aromatic residues, the term “calix[6]arenes” designates a calixarene with six aromatic residues, and the term “calix[8]arenes” designates a calixarene with eight aromatic residues. The aromatic rings composing any of these forms of calixarenes are typically described as forming a basket, as having an upper rim disposed above the aromatic ring, and as having a lower rim disposed below the aromatic ring ring and defined by the phenolic oxygen and its substituents, located in the para position relative to the upper-rim substituents.

[0061] Calix[4]arenes are the form of calixarenes used in the Examples reported below and the form particularly preferred for use in the inventive methods and compositions.. As the chemistry of grafting calixarenes of any number of aromatic residues to a substrate is the same, however, as is the chemistry of attaching styrene moieties and cross-linking polymers to calixarenes of any number of aromatic residues, it is anticipated that calix[4]arenes, calix[6]arenes, and calix[8]arenes can all be used in the inventive methods and compositions.

[0062] In some embodiments, the calixarenes used are calix[4]arenes. In some embodiments, the calixarenes used are calix[6]arenes. In some embodiments, the calixarenes used are calix[8]arenes.

[0063] Calix[4]arenes are the easiest and least expensive calixarenes to synthesize given current techniques and it is anticipated that they will be the most common form of calixarenes used to create grafted calixarenes anchoring catalysts to substrates. Chemistry is, however, continuously finding ways to reduce the cost and time needed to synthesize materials and it is anticipated that, as the time and cost to synthesize calix[6]arenes, calix[8]arenes, or both, that practitioners will choose to use them in some embodiments of the inventive methods and compounds. For clarity, it is noted that the synthesis of calix[6]arenes, and calix[8]arenes, and their properties, are already known in the art; the current limits on the use of these materials in embodiments of the inventive methods and compositions relate to the cost and time needed to synthesize them compared to the time and cost needed to synthesize calix[4]arenes.

[0064] As used herein, “not highly air sensitive” refers to a grafted calixarene material that does not irreversibly change its structure, its composition, or both, by being stored in contact with ambient air. As used herein, “irreversibly change” refers to a change in the structure of a material, the composition of the material, or both, that cannot be undone by heating the material. For example, water adsorption from air on the grafted calixarene material can be undone by desorbing water at temperatures below 200 ℃, without altering the grafted calixarene site structure and composition.

[0065] The term “metal-grafted” as used herein refers to a metal cation that has been covalently attached to a calixarene.Solid Supports

[0066] The “solid supports” referred to herein have an inorganic oxide surface which is available to react with the metal-grafted calixarene so as to cause anchoring of the latter. This can be done through alkoxide, hydroxide, or halogen substituents on the metal of the metal-grafted calixarene. In some embodiments, the oxide surface is of silicon dioxide, also known as “silica.” Other suitable solid supports include alumina, magnesium oxide, zirconia, aluminosilicate, and titania.

[0067] The term “porous” in reference to a solid support refers to a solid support having a surface area of 10 m2per gram or more, preferably 50 m2per gram or more, and still more preferably at least 100 m2per gram. The term “porous” thus refers to a solid support that has a high ratio of surface area to volume.

[0068] Both mesoporous and microporous materials can be used as supports. As set forth in Wikipedia, “mesoporous silica” is a form of silica that is characterized by its mesoporous structure, that is, having pores that range from 2 nm to 50 nm in diameter. According to IUPAC's terminology, “mesoporosity” refers to pore sizes between microporous (<2 nm) and macroporous (>50 nm). A preferred support is mesoporous silica that is characterized by 6 nm pore size (pore size refers to the pore diameter), and a surface area (“surface area” refers to BET surface area) of 500 m2per gram. References herein to “porous silica” refer to mesoporous silica with these characteristics. Such silica is widely used and is commercially available for such uses as liquid chromatographic applications, in the purification of organic compounds.

[0069] In some embodiments, the silica used as a solid support has been heated to a temperature above room temperature, and in some embodiments has been heated to a temperature up to and including 800 ℃.

[0070] As used herein, the term “functional group” is used in its usual meaning in chemistry to refer to a group of atoms (e.g., an ether, an aldehyde, a nitrile) in a molecule that are responsible for chemical characteristics or reactivity with other molecules. In some embodiments, the functional group is a homogeneous catalytic site. Metal Atoms, Metal Complexes, and Catalytic Activity

[0071] Any of the materials referred to in the claims of the ‘690 patent as a “polyvalent metallic or non-metallic atom” for grafting calixarenes to a solid support are suitable for grafting calixarenes to a solid support in embodiments of the present invention. In this regard,silicon, tungsten, niobium, titanium, zirconium, manganese, vanadium, chromium, tantalum, aluminum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum and iron atoms can be used to graft calixarenes to a solid support and to serve as homogeneous catalysts for reactions catalyzed by that metal atom. In some embodiments, the metal cation is a tetravalent metal cation, such as zirconium or hafnium. In some embodiments, the metal cation may be a trivalent cation, such as boron or gallium. In some embodiments, the metal cation can be Si(V) or P(V). In some embodiments, the polyvalent metal atom is titanium or aluminum. In some embodiments, the polyvalent metal atom is titanium. In some embodiments, the polyvalent metal atom is aluminum. Any particular metal cation of interest can be readily tested to see if it forms stable covalent connections and if the resulting materials are not highly air sensitive. Any metal cation that forms a stable covalent connection to a calixarene and a solid support, and that is not highly air sensitive is suitable for use as an embodiment of the inventive compositions and methods.

[0072] The metal atoms noted above serve as homogeneous catalysts. As noted in the Background, “homogeneous catalysts” are catalysts which are in the same phase as the reactants, and are typically catalysts which are in solution with the reactants. This generally means that the catalyst has to be isolated and recovered from the solution to be available for reuse. In the inventive methods and compositions, however homogeneous catalysts are covalently attached to a solid surface so that they do not flow with the solution and do not have to be recovered before the catalyst is available for use in another reaction cycle or to provide on-going catalysis where reactants are in continuous flowed. In some embodiments, the metal atom is covalently attached to a substituent itself covalently bound to a metal- grafted calixarene, which in turn is covalently bound to the porous, high surface area surface, such as silica, In some embodiments, the metal atom, or a metal complex comprising the metal atom, is covalently attached as a substituent on the lower rim of the calixarene and may be different from any metal atom used to covalently graft the calixarene to the porous surface. In some embodiments, the metal atom, or a metal complex comprising the metal atom, is covalently attached as a substituent on the upper rim of the calixarene and may be different from any metal atom used to covalently graft the calixarene to the porous surface (attachment of metal atoms, of metal complexes, or of polymerizable substituents to the upper rim of the calixarene can be accomplished by the methods set forth in Gutsche 1998, supra, and Gutsche 2008, supra). Methods of forming metal complexes are known in the art, as exemplified by, e.g., René, et al., J Fluorescence, 2019, 29:933-943. As used herein, thephrase “complex containing a metal atom” is used synonymously with the term “metal complex.”

[0073] In some embodiments, the metal atom grafting the calixarene to the porous surface is a Si atom, which is catalytically inactive and the catalytic metal atom is introduced as a catalytic metal-atom complex into the system as a substituent on the calixarene and / or as a monomer for polymerization (i.e. where the catalytic metal complex is covalently connected to a polymerizable moiety, which defines the monomer to be polymerized). This approach is advantageous because there is no additional interference from catalytically active metal atoms that are used for grafting (as noted, the Si atom used for grafting is catalytically inactive). Such interferences can otherwise catalyze undesired additional reactions, such as side reactions, beyond the desired reaction catalyzed by the metal complex. An exemplar method for grafting a calixarene to a porous surface is set forth in Example 9, below.

[0074] In all of the embodiments described above, the catalyst is held in place by being covalently attached to a grafted calixarence which in turn is stabilized on the porous surface by being covalently attached to one or more polymer strands that are crosslinked to others polymer strands or to other grafted calixarenes. And, in all of these embodiments, the amount of catalyst-bearing stabilized calixarenes that detach from the substrate and have to be recovered from the the solution is either eliminated or considerably reduced.

[0075] Further, as the polymer is bound to the calixarene in an ultrathin layer over the porous, high-surface area surface, the active site of the catalyst is accessible to reagents in any solution flowing over the polymer layer. And, the covalent attachment of the homogeneous catalyst to the polymer keeps the catalyst anchored during continuous flow procedures in which a solution containing reactants that undergo catalysis in the presence of the catalyst flow over the catalyst.

[0076] The retention of the catalyst in its immobilized position on the porous, high surface area oxide surface not only allows the catalyst to recycle quickly but, more importantly, also removes the need to recover the catalyst from the solution once the reactants have formed the reaction product. This advantageous combination of features makes the present invention a significant advance in the ability to provide homogeneous catalysts in an ultrathin layer robustly attached to porous, high surface area oxide supports, and a significant advance in using homogeneous catalysts.

[0077] Even prior to the development of methods of grafting calixarenes disclosed in the ‘690 patent, atoms of transition metals complexed with calixarenes were known to have catalytic effects on a number of reactions. For example, the ‘690 patent notes that catalytic effects of transition metals complexed with calixarenes had been shown for olefin rearrangements (Giannini et al., J. Am. Chem. Soc., 1999, 121:2797), cycloadddition of terminal alkanes (Ozerov et al., J. Am. Chem. Soc., 2000, 122:6423), and hydroformylation (Csok et al., J. Organometallic Chem., 1998, 570:23). While the calixarenes in those investigations were not immobilized, but were in homogeneous solution, with the metallic catalyst linked to the calixarene through one or more phenolic oxygens, the ‘690 patent stated that when the calixarenes or calixarene-related compounds are immobilized via a transition metal linker, the metal-phenolic oxygen connection is retained, and with it, catalytic activity. It is expected that the transition metals that graft the calixarenes to the substrates in the inventive compoistions will likewise retain catalytic activity.

[0078] In some embodiments, the metal atoms that serve as homogeneous catalysts are covalently bound as a substituent on the calixarene. In some embodiments, the metal atoms that serve as homogeneous catalysts graft the calixarenes to the substrate. In some embodiments, atoms of the same metal can be used both as a substituent on the calixarene and to graft the calixarene to the substrate. In some embodiments, atoms of one metal that can serve as a homogeneous catalyst can be a substituent on the calixarene while atoms of a second metal that can serve as a homogeneous catalyst serve to graft the calixarenes to the substrate. While it is currently difficult to have reaction conditions that allow both metal atom on such a calixarene provide catalytic activity at the same time, and thus typically currently require changing the reaction conditions to provide sequential catalytic activity, practitioners wishing to use such combinations of metal atoms can follow the teachings of this disclosure to stably attach such calixarenes to a porous oxide surface and conduct reactions catalyzed by those metal atoms.

[0079] Metals suitable for use as catalysts can be any transition metal known to be catalytically active. Catalytic metals useful for grafting calixarenes include titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum and iron. Silicon can be used to graft the calixarene to the porous substrate, but is catalytically inactive. As noted above, in such embodiments, a metal atom or metal complex containing the metal atom whose catalytic activity is desired is added as a substituent on the calixarene or covalentlyattached to a substituent on the calixarene. Alternatively, the metal atom whose catalytic activity is desired can be added as a substituent to a polymerizable monomer, and it becomes covalently attached to the calixarene through the previously mentioned polymerizable substituent after polymerization.

[0080] Methods of attaching metal atoms to calixarenes and of grafting calixarenes to suitable substrates are shown in the synthetic schemes set forth in the Examples. As the chemistry to form covalent connections of metal atoms to calixarenes is set forth in those schemes, it is expected that persons of skill will be able to substitute any given metal of their choice for the exemplar titanium and aluminum atoms used in the studies reported in the Examples to form calixarenes with the catalytic properties of their chosen metal. Polymerizable Substituents and Polymerizable Substituent Moieties

[0081] As used herein, the term “polymerizable substituent” refers to any substance that can covalently attach to a calixarene and can then either polymerize (that is, have a monomer that itself can polymerize covalently attach to the polymerizable substituent, which monomer than polymerizes to form a polymer strand covalently attached to the polymerizable substituent), or can covalently attach to an already-formed polymer strand.

[0082] In some embodiments, the polymerizable substituent is one that can attach to the lower rim of a calixarene by O-alkylation. Substances that can participate in polymerization and are thus suitable for use as polymerizable substituents in embodiments of the invention are well known in the art as exemplified by the references cited in the next section. The substances include, but are not limited to, functionalities consisting of styrene, acrylates, vinyl benzenes, divinyl benzenes, isopropyl benzenes, diisopropyl benzenes, and methacrylates. The polymerizable substituent attached to the calixarene has at least one double bonded carbon available for polymerization, even if it is not a crosslinking monomer, as it is attached to the calixarene by O-alkylation at a position which leaves the double bonded carbon available to polymerize to a monomer to form a polymer strand. For example, styrene, a non-crosslinking monomer, was used as an exemplar polymerizable substituent in the studies reported below. Styrenes were attached to calixarenes by O-alkylation and then contacted with polymerizable monomers which grew into polymer strands of various lengths chosen for the particular studies being conducted. While styrene was used as an exemplar polymerizable substituent in the studies underlying this disclosure, the same O-alkylation chemistry used to covalently attach styrenes to the calixarenes in the studies can be usedwithout change or with only minimal change immediately apparent to persons of skill to covalently attach other polymerizable substituents, such as the acrylates, vinyl benzenes, divinyl benzenes, isopropyl benzenes, diisopropyl benzenes, and methacrylates mentioned above, to calixarenes and to then attach polymer strands to the now-attached polymerizable substituent (or to attach polymerizable monomers to the now-attached polymerizable substituent). Accordingly, the studies reported in the Examples provide the practitioner with the information needed to create calixarenes covalently attached to a polymerizable substituent of their choice and to then covalently attach the polymerizable substituent to a polymer strand or or a polymerizable monomer that can then be polymerized to form a polymer strand. As used herein, a “polymerizable monomer” and a “monomer capable of polymerization” are used as synonyms.

[0083] As noted earlier, when a polymerizable substituent is covalently bound as a substituent on a calixarene, the polymerizable substituent no longer exists as a discrete entity but is now present as a derivative of the polymerizable substituent incorporated into a larger molecule with a chemical name that would reflect the combination of the calixarene and the polymerizable substituent. For ease of reference, a calixarene reacted with a divinyl benzene as the polymerizable substituent may sometimes be referred to herein as a “calixarene with a divinyl benzene substitutent,” or a “calixarene with a divinyl benzene moiety,” while a calixarene reacted with an acrylate as the polymerizable substituent may sometimes be referred to herein as a “calixarene with an acrylate substitutent,” or a “calixarene with an acrylate moiety,” while a calixarene reacted with a specific monomer, such as ethylene glycol dimethylacrylate (“EGDMA”), would be referred to as a “calixarene with an EGDMA substitutent,” or a “calixarene with an EGDMA moiety,” and so on. Monomers, Comonomers, Polymers, and Polymerization

[0084] Monomers are individual molecules with reactive bonds, which can be polymerized together to form covalent bonds between individual molecules so as to form a single molecule. A polymer is an assembly of monomers covalently linked together to form a single molecule. In some embodiments, the reactive bonds in monomers are unsaturated carbon- carbon bonds. In some embodiments, the unsaturated carbon-carbon bond is a carbon-carbon double bond.

[0085] Extensive information about both monomers capable of polymerization and the conditions under which such monomers polymerize, is available in the art, as exemplified bytexts such as G. Odian, PRINCIPLES OF POLYMERIZATION, John Wiley & Sons, Inc., Hoboken, NJ, 4thEd. 2004, (hereafter, “Odian”); V. Mishra, (ed.), POLYMERIZATION, Arcler Press, Burlington, Ontario, Canada, 2017; H. Kricheldorf, et al. (eds.), HANDBOOK OF POLYMER SYNTHESIS, CRC Press, 2ndEd., 2004, and W. Reed and A. Alb, (eds.), MONITORING POLYMERIZATION REACTIONS: FROM FUNDAMENTALS TO APPLICATIONS, Wiley, 2013. The entirety of each of these texts is hereby incorporated by reference.

[0086] In some embodiments, the inventive compositions and methods comprise grafted calixarenes copolymerized with a polymerizable substituent and a crosslinking monomer. In some embodiments, the inventive compositions and methods comprise grafted calixarenes copolymerized with a polymerizable substituent and two crosslinking comonomers. The Examples set forth the results of studies in which grafted calixarenes were covalently attached to crosslinked polymers. Example 3, for instance, reports studies in which styrenic substituents of grafted calixarenes were copolymerized with styrene (a linear polymer forming monomer) and 1,3-diisopropenylbenzene (a crosslinking monomer. A “crosslinking monomer” is generally considered in the art to be any monomer that has two or more carbons with double bonds per molecule). The ratio of styrene and 1,3-diisopropenylbenzene controlled the degree of polymer crosslinking. In some embodiments, divinyl benzene and diisopropenylbenzenes, by themselves, or together, are preferred monomers for connecting grafted calixarenes in the inventive compositions and methods. In some embodiments, the diisopropenylbenzene is 1,2- diisopropenylbenzene, 1,3- diisopropenylbenzene, 1,4- diisopropenylbenzene, or a combination of any two or all three of these. In some embodiments, members of the acrylate series are preferred monomers, by themselves or in combination with divinyl benzene or a diisopropenylbenzene, for connecting grafted calixarenes in the inventive compositions and methods. Members of the acrylate series that have reactivities close to that of styrene are discussed in the following paragraphs.

[0087] While 1,3-diisopropenylbenzene was used as an exemplar crosslinking monomer forming the crosslinking polymer in the studies discussed in the Examples, a number of other crosslinking monomers are known in the art and can be used in various embodiments of the inventive compositions and methods. Odian, supra, sets forth at page 487, Table 6-1, six different combinations of monomers that can copolymerize, including (1) styrene, methyl methacrylate, and vinylidene chloride, (2) methyl methacrylate, vinylidene chloride, and acrylonitrile, (3) styrene, acrylonitrile, and vinylidene chloride, (4) styrene, methyl methacrylate, and acrylonitrile, (5) styrene, acrylonitrile, and vinyl chloride, and (6) styrene,acrylonitrile, methyl methacrylate, and vinylidene chloride. Each of these combinations of monomers is expected to copolymerize and form crosslinking polymers stabilizing calixarenes grafted to a substrate.

[0088] Table 6-3, on page 492 of Odian, presents the relative reactivities of different monomers. It is expected that monomers whose relative reactivities are within 50 fold of each other, more preferably 20 fold, and most preferably within the same order of magnitude of each other, will serve as comonomers forming crosslinking polymers for use in the inventive compositions and methods. Referring to Table 6-3, the following pairs of monomers would be expected to serve as copolymers suitable use in different embodiments of the inventive compositions and methods: styrene and butadiene, styrene and methyl methacrylate, styrene and methyl vinyl ketone, styrene and acrylnitrile, butadiene and methyl methacrylate, butadiene and acrylonitrile, butadiene and methyl acrylate, butadiene and methyl methacrylate, methyl methacrylate and methyl acrylate, and methyl methacrylate and acrylonitrile. Many of these have crosslinking variants. (For example, EGDMA is a crosslinking variant of methyl methacrylate.) It is expected that persons of skill would immediately be aware of which of these monomers have crosslinking variants that can be readily substituted for the molecules described by name in this paragraph. Finally, as listed in Table 6-3, styrene and methyl methacrylate can serve as comonomers in polymerizing with crosslinking monomers. It is believed, however, that polymer strands composed of only crosslinking monomers are more rigid, and that more rigid polymer strands are useful in better stabilizing the grafted calixarenes connecting through the polymer web to multiple other grafted calixarenes. Thus, in preferred embodiments, all the monomers added to create the polymer strands (as opposed to the styrene covalently attached to the grafted calixarene) are crosslinking monomers.

[0089] Odian’s Table 6-1 states it is based on data from 1945 and from 1967, while its Table 6-3 is based on data in Table 6-2, which dates from 1945, 1989, and 1999. And, as noted, the edition of Odian cited above is itself from 2004. As these dates make evident, extensive information about monomers that can be used as copolymers and the conditions under which they can be polymerized has been known in the art for decades. It is expected that persons of skill in the art are familiar with the extensive information in the art regarding polymerization of monomers and the extensive information regarding the polymerization of comonomers, including quantities and proportions of comonomers to arrive at any given amount, and conditions for initiating polymerization of the comonomers.

[0090] As explained in Odian, supra: “[c]hain polymerization is initiated by a reactive species R* produced from some compound I termed an initiator. . . . . The reactive species, which may be a free radical, cation, or anion, adds to a monomer molecule by opening the p- bond to form a new radical, cation, or anion center, as the case may be.” Odian, supra, page 198 (emphasis in original). In the studies reported in the Examples, cationic initiators were utilized to polymerize styrene. For ease of comparison of the studies, all the studies used cationic initiators. As stated in the portion of Odian quoted above, however, polymerization of monomers such as styrene can also be achieved by using anionic initiators or free radical initiators. Not all three types of initators work to initiate polymerization of different unsaturated monomers. Some monomers can polymerize using anionic initiators or cationic initiators, but not using free radical initiators, while others polymerize with free radical initiators and anionic initiators, but not cationic initiators. Appropriate initiators to initiate polymerization of most common monomers polymerize is well known in the art, as exemplified by Odian, supra, at page 200, Table 3-1. See also, Morton, ANIONIC POLYMERIZATION: PRINCIPLES AND PRACTICE, Academic Press, 2012; Plesch (ed)., THE CHEMISTRY OF CATIONIC POLYMERIZATION, Pergamon Press, 2016; and Moad and Solomon, THE CHEMISTRY OF RADICAL POLYMERIZATION, Elsevier Science. 2ndEd., 2006. The contents of all of these publications is incorporated herein by reference. EXAMPLES

[0091] Examples 1 and 2 present two exemplar methods for immobilizing styrene- functionalized molecular catalytic sites to form a crosslinked surface-polymer layer on an oxide surface. The first of these uses a grafted titanium (Ti) atom, with a single styrenic substituent per Ti atom. The second uses a grafted aluminum (Al) atom, with two styrenic substituents per Al atom. The structures resulting from the approach employing Al atoms result in a higher degree of crosslinking and therefore an even more robust anchoring of the grafted sites to the oxide surface than do embodiments using a grafted Ti atom. Ti and Al form stable covalent connections and the resulting materials are not highly air sensitive. While these Examples set forth useful synthetic schemes, further studies set forth in the Examples following Examples 1 and 2 are more comprehensive. In the case of any difference in teachings of Examples 1 and 2 and the later Examples, the teachings in the later Examples are the ones to be followed.Example 1

[0092] Methods for making calixarenes with grafted metal atoms

[0093] Synthesis of a Ti-grafted calixarene polymerized with styrenic substituents

[0094] The first approach, using Ti, is described in Scheme 1 (the numbers bolded in this Example refer to the molecules and materials designated by those numbers in Scheme 1).

[0095] Scheme 1

[0096] Scheme 1. Synthesis of Ti-monostyrene-calix[4]arene-SiO2@800 with polymer coating: a) 4-vinylbenzyl iodide (1.5 equiv), CsF (1.1 equiv), DMF, 65 ℃, 21 h; b) Ti(OiPr)4 (1.0 equiv), toluene, RT, 1 h; c) SiO2@800, toluene, RT, 20 h; d) B(C6F5)3, styrene / 1,3- diisopropenylbenzene (0.95 / 0.05 v / v), DCM, RT, 17 h. SiO2@800 denotes silica that has been calcined at 800 ℃.

[0097] Using a new ligand 2 consisting of a mono-substituted calixarene triol with a styrenic substituent, a Ti(IV)-complex 3 was synthesized of this ligand. This molecular precursor complex 3 is grafted to the surface of silica so as to synthesize material 4. In the exemplar protocol shown in Scheme 1, the styrenic substituents in material 4 are copolymerized with alinear polymer forming agent (styrene), a crosslinking agent (1,3-diisopropenylbenzene), and, optionally, a styrene-functionalized molecular catalyst site (this can be for example a styrene- functionalized metal complex, which has desirable catalytic activity in homogeneous solution and for which immobilization is desired). In the absence of this optional site, only linear polymer forming agent and crosslinking agent are employed, so as to synthesize material 5.

[0098] To demonstrate the permanency of anchoring of sites in material 5, a continuous hot extraction with isopropanol was performed for a period of 24 hours by Soxhlet extraction. The results show that, without the polymer, in 4, all grafted calixarene sites were washed away after 24 h of IPA Soxhlet extraction, whereas with polymer, in 5, a significant amount of grafted calixarene sites remained grafted on the silica support. These data demonstrate that surface polymerization and crosslinking layer stabilized the grafted calixarene sites, allowing them to remain on the surface even during harsh, hot, continuous Soxhlet extraction.

[0099] Table 1. Calculated grafted calixarene coverages based on measured gravimetric weight loss between 120 ℃ and 750 ℃, for materials before and after 24 h IPA Soxhlet extraction.In synthesizing 5 in the study reported in this Example, the molar amount of crosslinking agent monomer to total added styrene-based monomer (i.e. crosslinking + linear-based polymerization monomer) was only 3.4 mol %. To make a more rigid polymer with an even greater retention of grafted calixarene sites, a greater content of crosslinking agent, such as 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% can be used. Further, other styrene- based cross-linking agents, such as 1,4-divinylbenzene, can be used. Finally, other methods of polymerization can be used, such as free radical polymerization.

[0100] Material 5 consists of grafted calixarene sites on a porous silica surface, which are polymerized through a crosslinked styrenic-polymer architecture to each other. The grafted Ti(IV)-calixarene sites on silica can be used as Lewis-acid catalytic sites for reactions known to be catalyzed by grafted Ti centers on siliceous environments, such as Meerwein-Ponndorf-Verley (“MPV”) reduction (see, e.g., van der Waal, et al., Catal. Lett. 1996, 41:63 – 67) and olefin epoxidation using organic hydroperoxide or hydrogen peroxide (see, e.g., Grosso- Giordano, et al., J. Am. Chem. Soc. 2019, 141(17):7090–7106; and Chem. Eur. J. 2007, 13:1210 − 1221). In these applications, the crosslinked styrenic polymer layer can also confer hydrophobicity to the environment surrounding the catalytically active site, which can facilitate catalysis (see, e.g., Di Iorio, et al., J. Am. Chem. Soc. 2020, 142(45):19379 – 19392; Gounder and Davis, J. Catal. 2013, 308:176 – 188). Alternatively, in the same surface polymerization approach used to synthesize 5, as mentioned above, a styrene-functionalized molecular catalyst site can be introduced to the crosslinked surface-polymer layer. This site is selected on the basis of itself conferring a desired catalytic activity for a desired reaction either in conjunction with the Ti centers present in 5, or on its own. In this case, during the polymerization reaction that is used for synthesis of 5, styrene monomers are at least partially substituted by this styrene-functionalized molecular catalyst site.

[0101] Synthesis of molecular precursor 2. CsF (0.50 g, 3.3 mmol) and p-tert- butylcalix[4]arene (1.95 g, 3.0 mmol) powders were dried at 100oC for 1 h under vacuum, and the solid mixture was dispersed in dry DMF (40 mL) at room temperature and stirred for 30 min. Afterwards, to this suspension, 4-vinylbenzyl iodide (1.10 g, 4.5 mmol) was added as a liquid (4-vinylbenzyl iodide was prepared from the corresponding chloride as described in René et al., Journal of Fluorescence 2019, 29:933 – 943). The resulting suspension was stirred at 65 °C for 21 h, and was subsequently quenched by addition of 2N HCl (40 mL). The mixture was extracted with CH2Cl2 (2 x 20 mL). The combined organic layers were washed with a saturated solution of Na2SO3(2 x 25 mL), water (2 x 25 mL), and were dried over MgSO4. After evaporation of the solvent in vacuo, the residue was purified by silica-gel chromatography using CH2Cl2 / hexanes (1:2) as eluent, to give 0.8 g (34 %) of 2. The resulting product could be recrystallized from MeCN.

[0102] 1H NMR (500 MHz, CDCl3): δ 1.21-1.22 (m, 36H), 3.41 (d, J = 13.6 Hz, 4H), 4.23 (d, J = 13.2 Hz, 2H), 4.35 (d, J = 13.2 Hz, 2H), 5.16 (s, 2H), 5.33 (d, J = 10.9 Hz, 1H), 5.85 (d, J = 17.6 Hz, 1H), 6.80 (dd, J = 17.6, 10.9 Hz, 1H), 6.98 (d, J = 2.3 Hz, 2H), 7.03 (s, 2H), 7.05 (d, J = 2.3 Hz, 2H), 7.12 (s, 2H), 7.55 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 9.38 (s, 2H), 9.99 (s, 1H).

[0103] 13C NMR (126 MHz, CDCl3): δ 31.30, 31.50, 31.53, 32.48, 32.99, 33.94, 34.02, 34.31, 78.94, 114.62, 125.61, 125.70, 125.75, 126.54, 126.79, 127.62, 128.01, 128.33, 129.41, 133.67, 135.14, 136.50, 138.20, 143.12, 143.63, 147.72, 148.36, 148.50, 149.31.

[0104] Synthesis of molecular precursor 3. Ti(OiPr)4 (0.09 mL, 0.3 mmol) was added dropwise under stirring to a dry toluene solution (3 mL) of 2 (229.5 mg, 0.3 mmol). The resulting solution was stirred at RT for 1 h, and the yellow solid product 3 was recovered with a quantitative yield by removing the solvent under vacuum.

[0105] 1H NMR (500 MHz, C6D6): δ 0.74 (s, 9H), 0.83 (s, 9H), 1.40 (s, 18H), 1.63 (d,= 5.8 Hz, 6H), 3.06 (d, J = 12.5 Hz, 2H), 3.35 (d, J = 12.5 Hz, 2H), 4.23 (d, J = 12.5 Hz, 2H), 5.07 (m, 4H), 5.26 (s, 2H), 5.60 (d, J = 17.6 Hz, 1H), 6.54 (dd, J = 17.6, 10.9 Hz, 1H), 6.89 (d, J = 6.4 Hz, 4H), 7.17 (m, 4H), 7.24 (d, J = 2.2 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H).

[0106] 13C NMR (126 MHz, C6D6): δ 26.53, 30.71, 31.07, 32.05, 33.64, 33.74, 33.96, 34.32, 34.40, 80.50, 80.64, 114.60, 123.98, 125.23, 125.70, 125.77, 126.62, 126.78, 127.08, 128.35, 128.57, 129.34, 130.85, 130.97, 131.39, 133.20, 135.65, 136.74, 137.90, 138.52, 144.12, 144.58, 148.26, 149.93, 156.22, 160.41.

[0107] Synthesis of 4: Grafted 3 on SiO2. SiO2@800 (Selecto Scientific; 32 – 63 μm silica particle size; N2 BET surface area of 498 m2 / g; pH ~ 7 as a 5% suspension in H2O) was calcined in air at 800 ℃ and stored in the glove box. 1 g of SiO2@800 and a magnetic stir bar were first loaded into a 25 mL Schlenk flask in a glovebox. This flask was then transferred to a Schlenk line filled with Ar, and a silica slurry was made by adding 5 mL of dry toluene under stirring. A solution of 3 (260 mg, 0.3 mmol) in 5 mL of dry toluene solution was added to the resulting silica slurry dropwise. The reaction mixture was stirred under Ar for 20 h. The solution was then decanted with freshly distilled toluene for at least five times, until the supernatant solution became colorless. Finally, the resulting solid 4 was recovered by filtration and dried under vacuum at RT for 1 h and at 80 °C for 3 h.

[0108] Synthesis of 5: Surface Polymerized Grafted Ti(IV)-Calixarene on SiO2. The polymerization reaction was carried out via cationic polymerization in CH2Cl2 initiated by B(C6F5)3at ambient temperature. Thus, B(C6F5)3(12.5 mg, 0.024 mmol) solution in CH2Cl2(2 mL) was added dropwise to a slurry of 0.5 g of Ti-calixarene-SiO2(4) in 8 mL of CH2Cl2under stirring. After the suspension stirred for 10 min, 2 mL of a styrene / 1,3- diisopropenylbenzene mixture (0.95 / 0.05 v / v) (so as to synthesize a cross-linked surface polymer) was introduced to the slurry under stirring, and the resulting suspension which was stirred for 18 h at room temperature. The material after surface polymerization was recovered by filtration and washed with CH2Cl2 (10 mL × 10). Note there was no gelation or visiblepolymerization in the solution phase. The resulting yellow / orange powder 5 was dried under dynamic vacuum at room temperature for 1 h and then at 80 °C for 3 h.

[0109] Leaching stress test. 50 mg of appropriate sample was continuously washed (24 h) with 15 mL of isopropanol at reflux temperature using a Soxhlet extraction apparatus. The results are shown in Figure 1.

[0110] Material 5 can be used as a catalyst. The conditions for catalysis involve the MPV reduction reaction of 2-chloroacetophenone and isopropanol under reflux. Thus, 172 mg of material 5 (corresponding to approximately 5 mol% of Ti sites relative to 2- chloroacetophenone) was added to a solution containing 77.3 mg (0.5 mmol) of 2- chloroacetophenone in 2.5 mL of dry isopropanol. The reaction was monitored by1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard. The molar amount of MPV-reaction product coincided with the molar depletion of 2-chloroacetophenone reactant. This mole balance closure is consistent with the fact that no other products were detected by1H NMR spectroscopy. The 2-chloroacetophenone conversion was 0% after 0 h; 6% after 18 h; 14% after 42 h; and 23% after 65 h. Fitting these conversion-versus-time data using linear least squares regression yielded a relationship: % 2-chloroacetophenone conversion = 0.347 * time (h)

[0111] These data demonstrate that the materials after polymerization such as 5 are catalytically accessible and active.

[0112] Scheme 1, above, shows polymerization under cationic conditions. Under these conditions, the styrenic moieties are very active and can engage and react with the calixarenes to result in the desired polymerization. Similarly, the styrenic moieties can engage and react with any homogeneous catalyst that has a reactivity similar to the known reactivity of the styrenic moieties. Further, as persons of skill will appreciate, styrenic moieties are similarly reactive under anionic conditions and under radical conditions. Thus, it is expected that the same reaction scheme can be used to provide the desired polymerization under any of these three sets of conditions. It is further expected that persons of skill are aware of how to set up any of the three conditions, and how to easily make any adjustments to the reaction conditions to accommodate their choice of cationic or free radical conditions. Example 2

[0113] Synthesis of an Al-grafted calixarene polymerized with styrenic substituents

[0114] In a second exemplar embodiment, an approach similar to that described above can be used to provide a grafted aluminum atom between silica and a styrene-substituted (in this case disubstituted) calixarene ligand, instead of the Ti atom used in Scheme 1. This second exemplar is shown in Scheme 2. Bolded numbers in this Example refer to the compounds designated by those numbers in Scheme 2.

[0115] Scheme 2

[0116] Scheme 2. Synthesis of Al-distyrene-calix[4]arene: a) 4-vinylbenzyl chloride (2.3 equiv), K2CO3 (1.2 equiv), KI (2.3 equiv), MeCN, reflux, 24 h; b) AlMe3 (2.0M in toluene, 1.0 equiv), toluene, RT, 15 min. c) grafting of complex 8 is performed as described in Nandi, et al., Proc Natl Acad Sci (USA) 2013, 110(7):2484 – 2489; d) surface polymerization of grafted material 9 is performed as described above in Scheme 1 for synthesis of 5, but usingonly 1,3-diisopropenylbenzene (320 μL) as monomer (instead of styrene / 1,3- diisopropenylbenzene mixture) per 0.5 gram of silica.

[0117] Synthesis of molecular precursor 7. The synthesis of 7 was based on a previous report (see Mendes, et al., Reactive & Functional Polymers, 2005, 65:9 – 21), with minor modifications as detailed below. A suspension of p-tert-butylcalix[4]arene (1.95 g, 3.0 mmol) and K2CO3(0.50 g, 3.6 mmol) was made in 50 mL of dry acetonitrile, and was refluxed for 1 hr. After cooling down to room temperature, 4-vinylbenzyl chloride (0.98 mL, 6.9 mmol) and KI (1.14 g, 6.9 mmol) were added. The resulting reaction mixture was refluxed for 24 h. The suspension was filtered and washed with acetonitrile. The filtrate was evaporated under reduced pressure, dissolved in DCM, washed with a saturated aqueous solution of Na2SO3(20 mL x 2), 2N HCl (20 mL x 2) and deionized water (30 mL x 2), and was finally dried over MgSO4. It was subsequently filtered and evaporated under reduced pressure. The resulting solid residue was recrystallized from hexanes to give 1.111 g (42%) of 7 as white crystals.

[0118] 1H NMR (500 MHz, CDCl3): δ 0.95 (s, 18H), 1.30 (s, 18H), 3.28 (d, J = 13.0 Hz, 4H), 4.29 (d, J = 13.0 Hz, 4H), 5.06 (s, 4H), 5.28 (d, J = 11.0 Hz, 2H), 5.78 (d, J = 17.7 Hz, 2H), 6.76 (dd, J = 17.7, 11.0 Hz, 2H), 6.80 (s, 4H), 7.05 (s, 4H), 7.30 (s, 2H), 7.41 (d, J = 8.1 Hz, 4H), 7.63 (d, J = 8.1 Hz, 4H).

[0119] 13C NMR (126 MHz, CDCl3): δ 31.15, 31.82, 31.86, 33.96, 34.07, 77.81, 114.06, 125.11, 125.65, 126.62, 127.61, 127.81, 132.72, 136.81, 136.95, 137.26, 141.46, 147.14, 149.88, 150.90.

[0120] Synthesis of 8. AlMe3(2.0M in toluene) (150 μL, 0.3 mmol) was slowly added (safety note: add slowly given violent methane evolution) to a stirred toluene solution (3 mL) of 7 (264.4 mg, 0.3 mmol). The resulting solution was stirred at RT for 1 h, and pale yellow solid 8 was recovered with in quantitative yield by removing the solvent under vacuum.

[0121] 1H NMR (500 MHz, C6D6): δ 0.44 (s, 3H), 0.76 (s, 18H), 1.44 (s, 18H), 3.08 (d, J = 12.4 Hz, 4H), 4.16 (d, J = 12.4 Hz, 4H), 5.05 (d, J = 11.0 Hz, 2H), 5.21 (s, 4H), 5.56 (d, J = 17.7 Hz, 2H), 6.50 (dd, J = 17.7, 11.0 Hz, 2H), 6.87 (s, 4H), 7.11 (m, 8H), 7.17 (s, 4H).

[0122] 13C NMR (126 MHz, C6D6): δ -10.65, 30.81, 32.21, 33.79, 34.06, 34.98, 79.68, 114.68, 124.96, 126.05, 126.45, 127.97, 128.16, 128.35, 130.72, 131.40, 133.27, 134.26, 136.68, 138.69, 140.29, 148.14, 148.60, 153.93.Example 3

[0123] This Example presents studies of the results of synthesizing Ti-monostyrene- calix[4]arene-SiO2@800 covalently attached to a polymer coating, and demonstrates covalent connectivity between the polymer and the grafted calixarene. Bolded numbers in this Example refer to the compounds designated by those numbers in Scheme 3, the compounds designated by those numbers in Fig. 6, or in both.

[0124] Scheme 3

[0125] Scheme 3. Synthesis of Ti-monostyrene-calix[4]arene-SiO2@800 with polymer coating: a) 4-vinylbenzyl iodide (1.5 equiv), CsF (1.1 equiv), DMF, 65 ℃, 21 h; b) Ti(OiPr)4 (1.0 equiv), toluene, RT, 1 h; c) SiO2@800, toluene, RT, 20 h; d) B(C6F5)3, styrene / 1,3- diisopropenylbenzene (0.95 / 0.05 v / v – for 12a and 0 / 100 v / v – for 12b) , DCM, RT, 18 h.

[0126] Scheme 3 summarizes the synthetic approach used for the studies reported in this Example (detailed information about the synthesis and analysis of each of the numbered reaction products is presented in Example 4.) The studies reported in this Example were performed later than the studies reported in Examples 1 and 2 and some numbering was used in the studies reported in this Example that is not consistent with the numbering used in theExamples 1 and 2. To avoid confusion, where materials in Scheme 3 are the same as materials identified by a different number in Scheme 1, the number designating the material in Scheme 3 is followed by parentheses stated that the material is the “same as” the material designated by a different number in Scheme 1, followed by the number in Scheme 1 for that material. Further, because some numbers used in Scheme 3 were also used in Scheme 2, but designate different materials than those numbers designated in Scheme 2, the numbers in this Example that were previously used in Scheme 2 to designate a different material have been differentiated in Scheme 3 by adding the letter “t” after the number.

[0127] Referring to Scheme 3, new ligand 9t was synthesized consisting of a mono- substituted calixarene triol with a styrenic substituent, and Ti(IV)-complex 10t was synthesized with this ligand. Molecular precursor complex 10t to was grafted to the surface of silica so as to synthesize material 11. Fig. 3a presents a13C CP / MAS spectrum of 11, and shows the calixarene ligand to be intact following grafting. In particular, resonances corresponding to styrenic substituents around 112 ppm are visible in Fig. 3a (an inset in Fig. 3a magnifies that portion to assist visualization), and demonstrate that those double bonds are indeed available for polymerization following calixarene grafting in material 11.

[0128] The styrenic substituents of grafted calixarenes in material 11 were copolymerized with styrene (a linear polymer forming monomer) and 1,3-diisopropenylbenzene (a crosslinking monomer). The ratio of styrene and 1,3-diisopropenylbenzene controls the degree of polymer crosslinking. Two particular examples of catalysts are material 12a (employing a styrene / 1,3-diisopropenylbenzene ratio of 0.95 / 0.05 v / v, which ends up being approximately 3.4 mol. % of crosslinking monomer in the polymer) and 12b (employing a styrene / 1,3-diisopropenylbenzene ratio of 0 / 100 v / v). 13C CP / MAS NMR spectra of 12a and 12b demonstrate are shown in Fig. 4a and 4b, and demonstrate disappearance of the styrenic- substituent resonance. This demonstrates covalent connection of the polymer and the grafted calixarene sites.

[0129] Thermogravimetric (TGA) analysis of 11 (which is the same as material 4 of Scheme 1 and is the parent material for 12a & 12b) is shown in Figure 5, and demonstrates a weight loss corresponding to 0.124 mmol calixarene / g, as summarized in Table 2.

[0130] Table 2. Summary of organic content as determined by TGA, and Ti content as determined by UV / Vis assay, of materials designated by their numbering in Scheme 3.aGrafted calixarene coverage for 12a and 12b after Soxhlet extraction (abbreviated as “AS” in the Table) assumes that reduction in weight loss is solely due to grafted calixarene removal via extraction and no polymer extraction. From the perspective of this assumption, the reported values are underestimates for material. (“After Soxhlet extraction” is sometimes abbreviated herein as “AS”).bControl experiments with TGA of isopropanol Soxhlet extracted silica exhibit the same weight loss profile, demonstrating a lack of grafted calixarenes in 11,AS.

[0131] Ti sites in grafted calixarene materials were quantified using a UV-Vis assay as described in Ramamurthy, M., et al., Microporous and Mesoporous Materials 2021, 319:111042; doi.org / 10.1016 / j.micromeso.2021.111042. The results indicated a calixarene per Ti ratio of 0.7 in 11. Without wishing to be bound by theory, the slightly smaller value of this ratio compared to unity is believed either to be the result of the difficulty of combusting calixarene ligands, a known consideration for this class of compounds and a reason why elemental analysis of this class of compounds is not reliable (i.e. they do not combust easily even up to TGA maximum temperature of 750 ℃), or that some calixarene was removed during toluene washing of 11 following calixarene grafting.

[0132] Data in Fig. 5 also demonstrate complete calixarene leaching after isopropanol Soxhlet extraction of 11, to synthesize 13 (Fig. 6 shows the structure of the materials referred to in this paragraph by numbers 13-15). The observed residual 2.8% weight loss for 13 in Fig. 5 is identical to the weight loss TGA profile observed for the silica support after the same Soxhlet extraction procedure (i.e. isopropoxy groups on silica). The same result of quantitative calixarene-ligand leaching was obtained upon Soxhlet extracting the grafted monomethoxy Ti(IV)-calixarene complex on silica 14.1H NMR spectroscopy of the extract showed the recovery of the calixarene ligands 9t (in the case of 11) and 15 (in the case of 14), demonstrating cleavage of the Ti-O-C bond. Material 13 (i.e. a material synthesized by Soxhlet extraction of 11) was also characterized by13C CP / MAS NMR spectroscopy, asshown in Figure 3b. These data confirm a lack of calixarene ligands and only isopropoxy ligands remaining in 13.

[0133] Ti analysis (with the UV-Vis assay cited above) reproducibly demonstrates the same Ti content of 0.185 mmol / g for material 11,AS (same as 13 in Fig.6) as for the precursor material 11. This confirms retention of the Si-O-Ti bond under the hot isopropanol reflux conditions of the Soxhlet extraction. The retention of the Si-O-Ti bond and cleavage of the Ti-O-C bond of grafted calixarene materials 11 and 14 under Soxhlet extraction conditions is schematically represented in Fig. 6.

[0134] TGA data of isopropanol Soxhlet-extracted 12a is shown in Fig. 7. The organic content of 12a prior to Soxhlet extraction was 20.9 wt. % (corresponding to 0.108 mmol calixarene / g and about 8 polymerized monomers per grafted calixarene), whereas after Soxhlet extraction, in material 12a,AS, this content was 16.8 wt. %. It is unclear whether this reduction corresponds to loss of oligomers of the polymer that are not attached to grafted calixarenes or whether it corresponds to leaching of calixarene. If it is assumed that all this reduction is due to calixarene leaching, the amount leached would correspond to loss of 59% of the grafted calixarenes in 12a, and this represents an upper bound for amount of calixarene lost during Soxhlet extraction. These data are summarized in Table 2. The crosslinked polymer in 12a therefore prevents the complete leaching of calixarene ligands, with at least 41% of the calixarene ligands remaining stable after Soxhlet extraction, as opposed to the results observed for 11, in which the polymer is absent.

[0135] TGA data of isopropanol Soxhlet-extracted 12b is shown in Fig. 8. The organic content of 12b prior to Soxhlet extraction was 24 wt. % (corresponding to 0.104 mmol calixarene / g and about 10 polymerized monomers per grafted calixarene), whereas after Soxhlet extraction, in material 12b,AS, this content was 22.4 wt. %. Assuming that all this reduction is due to calixarene leaching, the amount leached would correspond to a loss of 24% of the grafted calixarenes in 12b. These data are summarized in Table 2. The observed lower amount of organic leaching during isopropanol Soxhlet extraction for 12b compared with 12a is believed to be the result of the considerably higher crosslinking in the former. Experiments with materials synthesized with intermediate degrees of crosslinking of 7 mol. % and 14 mol. % showed an amount of organic leaching during isopropanol Soxhlet extraction corresponding to 57% and 42%, respectively, of grafted calixarenes. These leaching amounts are lower than the 59% of grafted calixarene amount leached observed forlight crosslinking of 3.5 mol. % in 12a above. They demonstrate a direct dependence of leaching on the crosslinking percentage in this class of materials. Example 4

[0136] This Example describes the synthesis of compounds discussed in the preceding Example.

[0137] Synthesis of molecular precursor 9t. CsF (0.50 g, 3.3 mmol) and p-tert- butylcalix[4]arene (1.95 g, 3.0 mmol) powders were dried at 100 ℃ for 1 h under vacuum, and the solid mixture was dispersed in dry DMF (40 mL) at room temperature and stirred for 30 min. To this suspension was then added 4-vinylbenzyl iodide (1.10 g, 4.5 mmol) as a liquid (4-vinylbenzyl iodide was prepared from the corresponding chloride as described in René et al., J Fluorescence 2019, 29:933 – 943). The resulting suspension was stirred at 65 °C for 21 h, and was subsequently quenched by addition of 2N HCl (10 mL). The mixture was extracted with CH2Cl2(2 x 20 mL). The combined organic layers were washed with a saturated solution of Na2SO3 (2 x 25 mL), water (2 x 25 mL), and were dried over MgSO4. After evaporation of the solvent in vacuo, the residue was purified by silica-gel chromatography using CH2Cl2 / hexanes (1:2) as eluent, to give 0.8 g (34 %) of 9. The resulting product could be recrystallized from MeCN.

[0138] 1H NMR (500 MHz, CDCl3): δ 1.21-1.22 (m, 36H), 3.41 (d, J = 13.6 Hz, 4H), 4.23 (d, J = 13.2 Hz, 2H), 4.35 (d, J = 13.2 Hz, 2H), 5.16 (s, 2H), 5.33 (d, J = 10.9 Hz, 1H), 5.85 (d, J = 17.6 Hz, 1H), 6.80 (dd, J = 17.6, 10.9 Hz, 1H), 6.98 (d, J = 2.3 Hz, 2H), 7.03 (s, 2H), 7.05 (d, J = 2.3 Hz, 2H), 7.12 (s, 2H), 7.55 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 9.38 (s, 2H), 9.99 (s, 1H).

[0139] 13C NMR (126 MHz, CDCl3): δ 31.30, 31.50, 31.53, 32.48, 32.99, 33.94, 34.02, 34.31, 78.94, 114.62, 125.61, 125.70, 125.75, 126.54, 126.79, 127.62, 128.01, 128.33, 129.41, 133.67, 135.14, 136.50, 138.20, 143.12, 143.63, 147.72, 148.36, 148.50, 149.31.

[0140] Synthesis of molecular precursor 10t. Ti(OiPr)4(0.09 mL, 0.3 mmol) was added dropwise under stirring to a dry toluene solution (3 mL) of 9t (229.5 mg, 0.3 mmol). The resulting solution was stirred at RT for 1 h, and the yellow solid product 10t was recovered with a quantitative yield by removing the solvent under vacuum.

[0141] 1H NMR (500 MHz, C6D6): δ 0.74 (s, 9H), 0.83 (s, 9H), 1.40 (s, 18H), 1.63 (d, J = 5.8 Hz, 6H), 3.06 (d, J = 12.5 Hz, 2H), 3.35 (d, J = 12.5 Hz, 2H), 4.23 (d, J = 12.5 Hz, 2H), 5.07(m, 4H), 5.26 (s, 2H), 5.60 (d, J = 17.6 Hz, 1H), 6.54 (dd, J = 17.6, 10.9 Hz, 1H), 6.89 (d, J = 6.4 Hz, 4H), 7.17 (m, 4H), 7.24 (d, J = 2.2 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H).

[0142] 13C NMR (126 MHz, C6D6): δ 26.53, 30.71, 31.07, 32.05, 33.64, 33.74, 33.96, 34.32, 34.40, 80.50, 80.64, 114.60, 123.98, 125.23, 125.70, 125.77, 126.62, 126.78, 127.08, 128.35, 128.57, 129.34, 130.85, 130.97, 131.39, 133.20, 135.65, 136.74, 137.90, 138.52, 144.12, 144.58, 148.26, 149.93, 156.22, 160.41.

[0143] Synthesis of 11: Grafted 10t on SiO2. SiO2@800 (Selecto Scientific; 32 – 63 μm silica particle size; N2 BET surface area of 498 m2 / g; pH ~ 7 as a 5% suspension in H2O) was calcined in air at 800 ℃ and stored in the glove box. 1 g of SiO2@800 and a magnetic stir bar were first loaded into a 25 mL Schlenk flask in a glovebox. This flask was then transferred to a Schlenk line filled with Ar, and a silica slurry was made by adding 5 mL of dry toluene under stirring. A solution of 10t (230 mg, 0.3 mmol) in 5 mL of dry toluene solution was added to the resulting silica slurry dropwise. The reaction mixture was stirred under Ar for 20 h. The solution was then decanted with freshly distilled toluene for at least five times, until the supernatant solution became colorless. Finally, the resulting solid 11 was recovered by filtration and dried under vacuum at RT for 1 h and at 80 °C for 3 h.

[0144] Synthesis of 12a,b: Surface Polymerized Grafted Ti(IV)-Calixarene on SiO2. The polymerization reaction was carried out via cationic polymerization in CH2Cl2 initiated by B(C6F5)3at ambient temperature. Thus, B(C6F5)3(12.5 mg, 0.024 mmol) solution in CH2Cl2(2 mL) was added dropwise to a slurry of 0.5 g of Ti-calixarene-SiO2(11) in 8 mL of CH2Cl2under stirring. After the suspension stirred for 10 min, 2 mL of a styrene / 1,3- diisopropenylbenzene mixture (0.95 / 0.05 v / v – for 12a) or 320 μL of 1,3- diisopropenylbenzene (100% crosslinking – for 12b) was introduced to the slurry under stirring, and the resulting suspension which was stirred for 18 h at room temperature. The material after surface polymerization was recovered by filtration and washed with CH2Cl2(10 mL × 10). Note there was no gelation or visible polymerization in the solution phase. The resulting yellow / orange powder was dried under dynamic vacuum at room temperature for 1 h and then at 80 °C for 3 h.

[0145] Soxhlet extraction stress test. 50 mg of appropriate sample was continuously washed (24 h) with 12 mL of isopropanol at reflux temperature using a Soxhlet extraction apparatus. All catalysts were subjected to a leaching stress test and dried (dried under dynamic vacuum at room temperature for 1 h and then at 120 °C for 3 h) prior to use in reactions. All materialsafter Soxhlet extraction are designated with an AS appended to their name; i.e. material X after Soxhlet extraction is designated as X,AS. Example 5

[0146] This Example discusses the catalytic properties of some of the compounds discussed in preceding Examples.

[0147] Materials 12a,AS and 12b,AS consisting of grafted calixarene sites on a porous silica surface were used as Lewis-acid catalytic sites for reactions known to be catalyzed by grafted Ti centers on siliceous supports, such as Meerwein-Ponndorf-Verley (“MPV”) reduction (van der Waal, et al., Catal. Lett. 1996, 41, 63 – 67) and olefin epoxidation using either organic hydroperoxide or hydrogen peroxide (Grosso-Giordano, et al., J Am Chem Soc, 2019,141(17):7090-7106; doi: 10.1021 / jacs.9b02160, and Zhang, et al., Chem. Eur. J. 2007, 13, 1210 – 1221; doi.org / 10.1002 / chem.200600752).

[0148] The conditions for MPV reduction catalysis involve reaction of 2-chloroacetophenone and isopropanol under reflux. Thus, a certain amount of grafted Ti(IV)-calixarene material in mg (corresponding to approximately 5 mol% of Ti sites relative to 2-chloroacetophenone) was added to a solution containing 77.3 mg (0.5 mmol) of 2-chloroacetophenone in 2.5 mL of dry isopropanol. The reaction was monitored by1H NMR spectroscopy using 1,3,5- trimethoxybenzene as an internal standard. The molar amount of MPV-reaction product coincided with the molar depletion of 2-chloroacetophenone reactant. This mole balance closure is consistent with the fact that no other products were detected by1H NMR spectroscopy.

[0149] Results of MPV reduction catalysis are shown in Fig. 9 (maximum ketone conversion is less than 25% in all of these data so that the kinetic data are in an initial rate period regime), and turnover frequency data are summarized in Table 3. These data demonstrate equal rates for the three catalysts being compared (all catalysts were Soxhlet extracted prior to use in catalysis, thereby having the nomenclature AS after their name), when normalized for Ti content (which was measured by the UV-Vis assay cited above). We conclude that the accessibility of the catalytic sites remains as high for the most open site, without polymer in catalyst 11,AS compared to the catalysts with crosslinked polymer, 12a,AS and 12b,AS. The same rate of the latter two further reinforces that the extent of crosslinking did not influence site accessibility.

[0150] Table 3. Summary of results from MPV reduction catalysis.

[0151] Catalysts with cyclohexene epoxidation with tert-butyl hydroperoxide as a probe reaction that reports on Lewis acidity were also investigated (Fig. 10 shows the epoxidation reaction conditions). Data in Figs. 11A-11D demonstrate nearly the same epoxidation rate for catalysts with crosslinked polymer 12a,AS, 12b,AS as well as control catalysts that lack polymer (13 and 14). These data are normalized on a per-Ti site basis in Table 4, below. Table 4 further summarizes the material balance (moles of epoxide formed per peroxide reacted), which is above 80% for all catalysts. The data in Table 4 demonstrate the same pseudo-first-order rate constant keff for all catalysts (within a tolerance of 15%). The results show that grafted-Ti sites in all four catalysts being compared are equally accessible, and there is no evidence of site blockage by the crosslinked polymer in 12a,AS and 12b,AS.

[0152] Table 4: Summary of Epoxidation Catalysis results*Measured via TGA, by calixarene lost, all others measured by UV-VIS assay

[0153] Reaction conditions: 20 mL of octane, 0.3 mL of cyclohexene (3 mmol), and 250 μL of dodecane (internal standard) were added to 25 mg of Ti-catalyst previously dried at 120 ℃ in vacuo. The suspension was stirred at 50 ℃ for 30 minutes. 0.1 mL of TBHP in decane (6 mmol) was added after the 30 minutes and 1.5 mL aliquots were collected at times 1 min, 10min, and 30 min. The aliquots were measured via gas chromatography with flame ionization detection (“GC-FID”).

[0154] The high degree of accessibility observed in the grafted Ti(IV)-calixarene sites after crosslinked polymerization is in stark contrast with sites immobilized in bulk crosslinked organic polymers. Those sites are largely inaccessible and require polymer swelling to generate some accessibility. The difference between those systems and the sites demonstrated in Examples 3-5 is believed to be due with the thin nanoscale nature of the crosslinked polymer layer attached to the grafted calixarene and reflects the novelty of the materials synthesis construct of this disclosure. Example 6

[0155] This Example reports studies of a materials construct in which there are two sites instead of one site per calixarene ligand. This has the repercussion of crosslinking the grafted calixarene to the crosslinked polymer network. It was posited that such a crosslinked (rather than linearly attached calixarene in 12a and 12b) calixarene ligand will be even more stable than one linearly attached, as in Examples 3-5. The compounds in this Example are referred by the numbers set forth under the respective structures in Scheme 4.

[0156] Scheme 4:

[0157] Scheme 4. a) 1-(2-chloroethyl)-4-vinylbenzene (2.3 equiv), K2CO3(1.2 equiv), KI (2.3 equiv), MeCN, reflux, 10 d; b) AlMe3 (2.0M in toluene, 1.0 equiv), toluene, RT, 1 h; c) grafting of complex 4-4 is performed as described in Nandi, et al., Proc Natl Acad Sci (USA), 2013, 110(7): 2484 – 2489, (SiO2@800, toluene, RT, 20 h); d) B(C6F5)3, 1,3- diisopropenylbenzene, DCM, RT, 18 h.

[0158] New ligand 4-3 was synthesized consisting of a disubstituted calixarene diol with two styrenic substituents, and synthesized Al(III)-complex 4-4 with this ligand. Molecular precursor complex 4-4 was then grafted to the surface of silica so as to synthesize material 4- 5.

[0159] Studies of the dual-site grafted calixarene leveraged on the studies reported in Examples 3-5, which demonstrated less leaching of grafted sites with 100% crosslinking monomer (during Soxhlet extraction with hot isopropanol). The styrenic substituents of grafted calixarenes in material 4-5 were copolymerized with 1,3-diisopropenylbenzene (a crosslinking monomer), to synthesize material 4-6. Fig. 12 shows TGA data for materials 4-5 and 4-6, and demonstrates the weight change upon incorporation of crosslinked polymer tothe grafted calixarene material 4-5. A grafted calixarene coverage of 0.118 mmol / g was calculated for 4-5 (and 0.099 mmol / g for 4-6), and a polymer weight percentage of 16.1% in 4-6 (corresponding to polymerization of about a third of the crosslinking monomer added and about 10.2 crosslinking monomers per grafted calixarene polymerized).

[0160] Soxhlet extraction of 4-5 in hot isopropanol for 24 h led to material 4-5,AS. The TGA weight loss profiles for these two materials are shown in Fig. 13. These data (like the data for the corresponding Ti(IV)-calixarene material before polymerization 11 (which is the same material designated as 4) in Fig. 5) demonstrate the complete leaching of calixarene ligands in 4-5 upon Soxhlet extraction (the residual mass loss in 4-5,AS is attributed to isopropoxy groups grafted on silica).

[0161] TGA data for the corresponding Soxhlet extraction of material 4-6 (after polymerization of 4-5) is shown in Fig. 14. The material after Soxhlet extraction (4-6,AS) shows nearly the same organic weight loss during TGA as the one before (material 4-6). The grafted calixarene density calculated on the basis of data in Fig.14 is 0.090 mmol / g in 4- 6,AS, which represents over 91% retention of grafted calixarene sites during Soxhlet extraction of 4-6. These data represent a breakthrough in the stability of grafted calixarene sites, and demonstrate the crucial nature of crosslinking for retaining these sites. Using the same approach, reaction, and conditions as described in Section 1, we were able to demonstrate 4-6,AS as an active MPV reduction catalyst, having a TOF value of over 20-fold higher than the corresponding grafted Ti(IV)-calixarene materials (TOF value of 1.139 h-1). This datum is shown in Fig. 15, and reflects proficiency of Al cations grafted on silica in catalyzing MPV reduction, relative to Ti cations grafted on silica.

[0162] Synthesis of molecular precursor 4-3. A suspension of p-tert-butylcalix[4]arene (1.95 g, 3.0 mmol) and K2CO3 (0.50 g, 3.6 mmol) was made in 50 mL of dry acetonitrile, and was refluxed for 1 h. After cooling down to room temperature, 1-(2-chloroethyl)-4- vinylbenzene (1.15 g, 6.9 mmol) and KI (1.14 g, 6.9 mmol) were added. The resulting reaction mixture was refluxed for 24 h. The suspension was filtered and washed with acetonitrile. The filtrate was evaporated under reduced pressure, dissolved in DCM, washed with a saturated aqueous solution of Na2SO3(20 mL x 2), 2N HCl (20 mL x 2) and deionized water (30 mL x 2), and was finally dried over MgSO4. It was subsequently filtered and evaporated under reduced pressure. The resulting solid residue was recrystallized from hexanes to give 1.28 g (47%) of 4-3 as white crystals.

[0163] 1H NMR (500 MHz, CDCl3): δ 0.97 (s, 18H), 1.31 (s, 18H), 3.33 (d, J = 13.0 Hz, 4H, Ar-CH2-Ar), 3.38 (t, J = 7.6 Hz, 4H, Ar-CH2-CH2-O-), 4.21 (t, J = 7.6 Hz, 4H, Ar-CH2-CH2- O-), 4.30 (d, J = 13.0 Hz, 4H, Ar-CH2-Ar), 5.21 (d, J = 10.8 Hz, 2H, Ar-CH=CH2(cis)), 5.71 (d, J = 17.6 Hz, 2H, Ar-CH=CH2(trans)), 6.70 (dd, J = 17.6, 10.8 Hz, 2H, Ar-CH=CH2), 6.81 (s, 4H), 7.07 (s, 4H), 7.33 – 7.40 (m, 8H), 7.35 (s, 2H, Ar-OH).

[0164] 13C NMR (126 MHz, CDCl3): δ 31.16 (6C, -C-CH3), 31.86 (6C, -C-CH3), 31.93 (4C, Ar-CH2-Ar), 33.97 (2C, -C-CH3), 34.06 (2C, -C-CH3), 36.36 (2C, Ar-CH2-CH2-O-), 77.19 (2C, Ar-CH2-CH2-O-), 113.43 (2C, Ar-CH=CH2), 125.19 (4C, CH, calixarenic), 125.64 (4C, CH, calixarenic), 126.54 (4C, CH, styrenic), 128.00 (4C), 129.42 (4C, CH, styrenic), 132.65 (4C), 136.02 (2C), 136.76 (2C, Ar-CH=CH2), 137.77 (2C), 141.53 (2C), 146.95 (2C), 150.13 (2C), 150.82 (2C).

[0165] Synthesis of 4-4. AlMe3 (2.0M in toluene) (150 μL, 0.3 mmol) was slowly added (safety note: add slowly given violent methane evolution) to a stirred toluene solution (3 mL) of 4-3 (273 mg, 0.3 mmol). The resulting solution was stirred at RT for 1 h, and pale yellow solid 4-4 was recovered with in quantitative yield by removing the solvent under vacuum.

[0166] 1H NMR (500 MHz, C6D6): δ 0.26 (s, 3H), 0.78 (s, 18H), 1.53 (s, 18H), 3.19 (m, 4H), 3.40 (d, J = 12.2 Hz, 4H), 4.49 (d, J = 12.2 Hz, 4H), 4.52 (m, 4H), 5.08 (d, J = 10.9 Hz, 2H), 5.60 (d, J = 17.6 Hz, 2H), 6.57 (dd, J = 17.6, 10.9 Hz, 2H), 6.78 (d, J = 8.1 Hz, 4H), 7.02 (s, 4H), 7.14 (d, J = 8.1 Hz, 4H), 7.35 (s, 4H).

[0167] 13C NMR (126 MHz, C6D6): δ -11.32, 30.83, 32.30, 33.86, 34.19, 35.33, 36.09, 79.40, 113.55, 125.10, 126.41, 126.90, 127.97, 128.35, 129.56, 130.73, 132.97, 135.96, 136.64, 136.95, 140.51, 148.84, 149.80, 154.10.

[0168] Synthesis of 4-5: Grafted 4-4 on SiO2. SiO2@800 (Selecto Scientific; 32 – 63 μm silica particle size; N2 BET surface area of 498 m2 / g; pH ~ 7 as a 5% suspension in H2O) was calcined in air at 800 ℃ and stored in the glove box. 1 g of SiO2@800 and a magnetic stir bar were first loaded into a 25 mL Schlenk flask in a glovebox. This flask was then transferred to a Schlenk line filled with Ar, and a silica slurry was made by adding 5 mL of dry toluene under stirring. A solution of 4-4 (285 mg, 0.3 mmol) in 5 mL of dry toluene solution was added to the resulting silica slurry dropwise. The reaction mixture was stirred under Ar for 20 h at RT. The solution was then decanted with freshly distilled toluene for at least five times, until the supernatant solution became colorless. Finally, the resulting solid 4-5 was recovered by filtration and dried under vacuum at RT for 1 h and at 80 °C for 3 h.

[0169] Synthesis of 4-6: Surface Polymerized Grafted Al(III)-Calixarene on SiO2. The polymerization reaction was carried out via cationic polymerization in CH2Cl2 initiated by B(C6F5)3at ambient temperature. Thus, B(C6F5)3(12.5 mg, 0.024 mmol) solution in CH2Cl2(2 mL) was added dropwise to a slurry of 0.5 g of Al-calixarene-SiO2(4-5) in 8 mL of CH2Cl2 under stirring. After the suspension stirred for 10 min, 320 μL of 1,3- diisopropenylbenzene mixture (to synthesize a cross-linked surface polymer) was introduced to the slurry under stirring, and the resulting suspension which was stirred for 18 h at room temperature. The material after surface polymerization was recovered by filtration and washed with CH2Cl2 (12 mL × 8). Note there was no gelation or visible polymerization in the solution phase. The resulting pale-yellow powder 4-6 was dried under dynamic vacuum at room temperature for 1 h and then at 80 °C for 3 h.

[0170] Leaching stress test. 50 mg of appropriate sample was continuously washed (24 h) with 15 mL of isopropanol at reflux temperature using a Soxhlet extraction apparatus. Example 7

[0171] This Example presents an approach that involves grafting a calixarene with a substituent that is neither a grafting metal atom nor a styrenic substituent that is involved in the surface polymerization. The compounds in this Example are referred by the letters set forth under the respective structures in Scheme 5, below.

[0172] Scheme 5

[0173] Scheme 5: Steps i-iii of Scheme 5 correspond to steps b-d of Scheme 4. Step iv of Scheme 5 is an IPA Soxhlet extraction, reflux, 24 h.

[0174] An example of such a calixarene is shown in A in Scheme 5, which bears a propoxy substituent. One familiar with the art will recognize that in general this substituent can be different from propoxy and can be a metal complex (consisting of a metal atom complexed to an organic ligand) that is covalently attached to the calixarene lower-rim oxygen. Such a calixarene provides the ability to introduce catalytic metal complexes as substitutents onto grafted calixarenes (i.e. the propoxy group in Scheme 5 can be viewed as a general “R” group, which can also represent a catalytically active metal complex).

[0175] In one set of embodiments, an “R” group is anchored as the third substituent on the calixarene via grafting, while a Si atom is used as the grafting atom between the oxide- support surface (e.g., silica. Using Si as an atom to graft a calixarene to an oxide-supportsurface was shown in U.S. Patent No. 6,951,690). This combination results in a catalytically inert grafting metal atom (i.e. the Si), so that the catalytic activity of the grafted calixarene is provided solely by the metal atom of the “R” substituent. This permits the practitioner to readily generate calixarenes with any particular metal atom the practitioner wishes to use as the catalyst by swapping out the metal in the R group metal complex.

[0176] From another perspective, the trisubstituted calixarene A creates an open grafted Al site in materials C (before polymerization) and D (after polymerization), which is synonymous with having an open coordination site readily available at the grafted Al- calixarene site. This ultimately renders the open site in material E (obtained by subjecting D to IPA Soxhlet extraction), to be more catalytically active for MPV reduction than the corresponding closed site in material 10 of Scheme 2. These data as well as the relevant syntheses are further described below.

[0177] This permits the practitioner to readily generate calixarenes with any particular metal atom the practitioner wishes to use as the catalyst by swapping out the metal in the R group metal complex.

[0178] Synthesis of A. A solution of 1,3-disubstituted calix[4]arene 4-6 (as that material is referred to in Scheme 4, 1.30 g, 1.475 mmol) and dry Ba(OH)2(0.98 g, 5.75 mmol) was made in 50 mL of dry DMF, and was stirred at 70 ℃ for 1 h. After cooling down to room temperature, n-propyl bromide (4 mL, 44.25 mmol) was added. The resulting reaction mixture was stirred at 70 ℃ for 3 h and the progress of the reaction was tracked by thin layer chromatography (“TLC,” hexanes / EtOAc = 30 / 1). The reaction mixture was filtered and washed with dimethylformamide. The filtrate was diluted with dichloromethane, organic layer was washed with diionized water (40 mL x 3) and dried over MgSO4. It was subsequently filtered and evaporated under reduced pressure. The resulting solid residue was recrystallized from hexanes to give 0.6 g (44%) of 7 as white crystals.

[0179] 1H NMR (500 MHz, CDCl3): δ 0.32 (t, J = 7.6 Hz, 3H), 0.84 (s, 18H), 1.34 (s, 18H), 1.79 (sext, J = 7.6 Hz, 2H), 3.08 (d, J = 12.7 Hz, 2H), 3.25 (d, J = 13.1 Hz, 2H), 3.56 (m, 2H), 4.29 (d, J = 12.7 Hz, 2H), 4.40 (d, J = 13.1 Hz, 2H), 4.72 (d, J = 11.0 Hz, 2H), 4.88 (d, J = 11.0 Hz, 2H), 5.27 (d, J = 10.9 Hz, 2H), 5.47 (s, 1H), 5.78 (d, J = 17.6 Hz, 2H), 6.54 (m, 4H), 6.75 (dd, J = 17.6, 10.9 Hz, 2H), 7.07 (s, 2H), 7.12 (s, 2H), 7.42 (d, J = 8.2 Hz, 4H), 7.46 (d, J = 8.2 Hz, 4H).

[0180] 13C NMR (126 MHz, CDCl3): δ 9.37, 22.48, 31.18, 31.41, 31.68, 31.84, 31.91, 33.84, 34.01, 34.26, 76.32, 77.93, 114.04, 124.94, 125.04, 125.17, 125.68, 126.35, 129.24, 129.66, 132.00, 132.59, 136.06, 136.78, 137.15, 137.42, 141.74, 145.57, 145.60, 150.85, 151.44, 154.13.

[0181] Synthesis of B. AlMe3 (2.0M in toluene) (150 μL, 0.3 mmol) was added slowly to a stirred toluene solution (5 mL) of A (277 mg, 0.3 mmol). The resulting solution was stirred at RT for 15 min, and the orange solid B was recovered in quantitative yield by removing the solvent under vacuum. The1H NMR spectrum of recovered B in C6D6 solvent is shown in Fig. 17.

[0182] Synthesis of F: Grafted AlMe3on silica. A simple control material, consisting of grafted trimethyl aluminum on silica, was made resulting in material F, as follows. SiO2@800 (Selecto Scientific; 32 – 63 μm silica particle size; N2 BET surface area of 498 m2 / g; pH ~ 7 as a 5% suspension in H2O) was calcined in air at 800 ℃ and stored in the glove box. 600 mg of SiO2@800 and a magnetic stir bar were first loaded into a 25 mL Schlenk flask in a glovebox. This flask was then transferred to a Schlenk line filled with Ar, and a silica slurry was made by adding 6 mL of dry toluene under stirring. Then, 90 μL of 2.0 M solution of AlMe3in toluene solution was added to the resulting silica slurry dropwise. The reaction mixture was stirred under Ar for 20 h at RT. The solution was then decanted with 3 mL of freshly distilled toluene two times. Finally, the resulting solid F was recovered by drying under vacuum at RT for 1 h and at 120 °C for 1 h.

[0183] Control material F was subsequently converted to a control G consisting of grafted aluminum isopropoxide on silica, as described below. This material had lower catalytic activity for MPV reduction compared to grafted calixarene materials resulting from the inventive methods.

[0184] Synthesis of G. 300 mg of material F was continuously washed (24 h) with 15 mL of isopropanol at reflux temperature using a Soxhlet extraction apparatus. Then, resulting material G was dried under vacuum at RT for 1 h and at 120 ℃ for 3h.Example 8

[0185] This Example reports the results of studies comparing the catalytic activity of materials reported in Example 7 against control compound G.

[0186] Data from studies of the catalytic activity of some embodiments of the inventive compositions and methods when conducting MPV reduction catalysis under the same conditions as detailed above in the earlier examples are set forth in Fig. 16 and Table 5.

[0187] Table 5. TOF of Al-catalysts

[0188] The data shown in Fig. 16 and Table 5 indicate that the catalysts of the embodiments of the inventive method shown in Examples 6 and 7 (E and 4-6,AS) are more active than the control synthesized in Example 7, (G), which consists of grafted aluminum isopropoxide on silica. The data also demonstrate the utility of synthesizing an open site in E, which is more catalytically active than the closed site in 4-6,AS. This demonstrates control of catalysis through the coordination environment in a stable catalyst (both E and 4-6,AS underwent Soxhlet extraction in neat isopropanol and retained their grafted calixarene complexes through this corrosive exhaustive washing step), exemplifying the robustness and stability of the catalyst-bearing grafted calixarenes provided by the inventive methods. Example 9

[0189] This Example presents a method for grafting a calixarene to a substrate using a Si atom as the atom to which which calixarene grafting occurs. In this case, the procedure of the ‘690 patent is followed in the following way. The silica surface is activated for calixarene grafting via treatment with a Si-Cl containing compound, such as silicon tetrachloride. An excess of such a compound is used relative to the numbers of silanols on silica (5 silanols per nm2) together with an excess of a base such as triethylamine (where the triethylamine is also present in more than two-fold excess relative to the silicon tetrachloride), in an inert reaction solvent such as toluene or benzene. Any base can be used whether it is soluble or insoluble in the reaction solvent, but a soluble base is preferred because it is all available due to its dissolution, with triethylamine as a preferred embodiment. Following silicon tetrachloridecondensation with the silica surface at mild temperatures in the range of room temperature up to about 80 °C (which liberates HC1 that is immediately neutralized by the base (for example, in the case of triethylamine, by formation of a triethlammonium chloride salt), the calixarene alcohol is introduced. At least one OH group of the calixarene alcohol reacts with a Si-Cl group on the activated silica surface at mild temperatures in the range of room temperature up to about the temperature of toluene reflux. This causes calixarene grafting via formation of a Si-Ocaiixarene bond, and produces a material that contains no catalytically active metal atom as the atom that participates in calixarene grafting (i.e. the Si atom participating in calixarene grafting in catalytically inactive). Such an approach successfully grafts calixarenes A, 4-3, 9t, and 7 as those compounds are designated in the preceding Examples.

[0190] This method can in general be used to graft any calixarene bearing polymerizable substituents because the triethylamine protects the double bonds of the polymerizable substituents from degradation by the liberated HC1 (i.e. in the absence of the base, the HC1 would react with the double bonds of the polymerizable substituent). In this case, after calixarene anchoring, polymerization can be performed and the HCI salt of the base can be removed via washing with a suitable polar solvent.

[0191] This approach is particularly useful when the catalytic metal atom is introduced as a catalytic metal-atom complex into the system as a substituent on the calixarene and / or as a monomer for polymerization (i.e. where the catalytic metal complex is covalently connected to a polymerizable moiety, which defines the monomer to be polymerized). This approach is advantageous under these circumstances because there is no additional interference from catalytically active metal atoms that are used for grafting (i.e. the Si atom used for grafting is catalytically inactive). Such interferences can otherwise catalyze undesired additional reactions, beyond the desired reaction catalyzed by the metal complex.

[0192] It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes.

Claims

condensation with the silica surface at mild temperatures in the range of room temperature up to about 80 ℃ (which liberates HCl that is immediately neutralized by the base (for example, in the case of triethylamine, by formation of a triethlammonium chloride salt), the calixarene alcohol is introduced. At least one OH group of the calixarene alcohol reacts with a Si-Cl group on the activated silica surface at mild temperatures in the range of room temperature up to about the temperature of toluene reflux. This causes calixarene grafting via formation of a Si-Ocalixarenebond, and produces a material that contains no catalytically active metal atom as the atom that participates in calixarene grafting (i.e. the Si atom participating in calixarene grafting in catalytically inactive). Such an approach successfully grafts calixarenes A, 4-3, 9t, and 7 as those compounds are designated in the preceding Examples. [0190] This method can in general be used to graft any calixarene bearing polymerizable substituents because the triethylamine protects the double bonds of the polymerizable substituents from degradation by the liberated HCl (i.e. in the absence of the base, the HCl would react with the double bonds of the polymerizable substituent). In this case, after calixarene anchoring, polymerization can be performed and the HCl salt of the base can be removed via washing with a suitable polar solvent. [0191] This approach is particularly useful when the catalytic metal atom is introduced as a catalytic metal-atom complex into the system as a substituent on the calixarene and / or as a monomer for polymerization (i.e. where the catalytic metal complex is covalently connected to a polymerizable moiety, which defines the monomer to be polymerized). This approach is advantageous under these circumstances because there is no additional interference from catalytically active metal atoms that are used for grafting (i.e. the Si atom used for grafting is catalytically inactive). Such interferences can otherwise catalyze undesired additional reactions, beyond the desired reaction catalyzed by the metal complex. [0192] It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes.CLAIMS 1. A composition comprising a first calixarene having a lower rim and an upper rim, which first calixarene is substituted with a first polymerizable substituent, which first calixarene is (a) covalently bound through said polymerizable substituent to a first crosslinked polymer strand 4 to 200 monomers in length, and (b) covalently bound through a metal atom to a porous oxide surface.

2. The composition of claim 1, wherein said metal atom through which said first calixarene is covalently bound to said porous oxide surface is titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or iron.

3. The composition of claim 1, wherein said metal atom through which said first calixarene is covalently bound to said porous oxide surface is aluminum, titanium, or silicon.

4. The composition of claim 1, wherein said metal atom through which said first calixarene is covalently bound to said porous oxide surface is aluminum or titanium.

5. The composition of claim 1, wherein said porous oxide surface is silica, alumina, magnesium oxide, zirconia, aluminosilicate, or titania.

6. The composition of claim 1, wherein said porous oxide surface is silica.

7. The composition of claim 1, wherein said porous oxide surface is silica that has been dehydroxylated prior to calixarene attachment via preheating up to 800 ℃.

8. The composition of claim 1, further wherein said first calixarene has a metal atom or a metal complex substituted on said lower rim or on said upper rim.

9. The composition of claim 8, wherein said metal atom is substituted on said lower rim of said first calixarene and said metal atom is a titanium, aluminum, zirconium, hafnium, boron, gallium, or germanium atom.

10. The composition of claim 8, wherein said metal complex is substituted on said upper rim of said first calixarene and said metal atom is a titanium, aluminum, zirconium, hafnium, boron, gallium, or germanium atom.

11. The composition of claim 1, wherein said first polymerizable substituent of said first calixarene has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate, or a crosslinking variant of one of these.

12. The composition of claim 1, further comprising a second calixarene having a lower rim and an upper rim, which second calixarene is substituted with a second polymerizable substituent, which second calixarene is (a) covalently bound through said polymerizable substituent to a second crosslinked polymer strand, and (b) covalently bound through a metal atom to a porous oxide surface.

13. The composition of claim 1, wherein said first crosslinked polymer strand of 4 to 200 monomers in length is attached to a second polymerizable substituent on a lower rim of a second calixarene covalently bound through a metal atom to said porous oxide surface.

14. The composition of claim 13, wherein said first crosslinked polymer strand is 4 to 100 monomers in length.

15. The composition of claim 13, wherein said first crosslinked polymer strand is 4 to 50 monomers in length.

16. The composition of claim 13, wherein said first crosslinked polymer strand is 8 to 25 monomers in length.

17. The composition of claim 13, wherein said first crosslinked polymer strand is 8 to 12 monomers in length.

18. The composition of claim 1, wherein said first crosslinked polymer strand is covalently attached to a second crosslinked polymer strand, thereby forming one continuous crosslinked polymer strand, which one continuous crosslinked polymer strand is also covalently attached to a polymerizable substituent on a lower rim of a second calixarene covalently bound through a metal atom to said porous oxide surface.

19. The composition of claim 18, wherein said second polymerizable substituent of said second calixarene has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate, or a crosslinking variant of one of these.

20. The composition of claim 1, wherein said first polymerizable substituent of said first calixarene has a functionality consisting of styrene, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate and wherein said functionality is covalently bound to a first crosslinked polymer strand of 4 to 200 monomers in length covalently attached to a second polymerizable substituent, which second polymerizable substituent is covalently attached to a second calixarene covalently bound through a metal atom to said porous oxide surface.

21. The composition of claim 20, wherein said first polymerizable substituent of said first calixarene has a functionality consisting of styrene.

22. The composition of claim 21, wherein said first polymerizable substituent of said first calixarene has a functionality consisting of styrene and said styrenic functionality is covalently attached to a crosslinking polymer strand composed of monomers of, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, styrene, or methacrylate, or of monomers of two or more of these, provided that, if said crosslinking polymer strand also comprises a plurality of crosslinking monomers.

23. The composition of claim 1, wherein said first calixarene is material 4 of Scheme 1.

24. The composition of claim 23, wherein said material 4 of Scheme 1 is covalently attached at said first styrenic moiety to a first crosslinked polymer strand of 4 to 200 monomers in length covalently attached to a second stryrenic moiety, which second stryrenic moiety is substituted on second calixarene covalently bound through a metal atom to a porous oxide surface.

25. The composition of claim 1, wherein said composition is material E of Scheme 6.

26. The composition of claim 1, wherein said composition is material 4-6 of Scheme 4.

27. The composition of claim 1, wherein said composition is material 11, 12a, or 12b of Scheme 3.

28. The composition of claim 1, wherein said first calixarene is a calix[4]arene.

29. The composition of claim 1, wherein said first calixarene is a calix[6]arene.

30. The composition of claim 1, wherein said first calixarene is a calix[8]arene.

31. A composition comprising a plurality of calixarenes, wherein each calixarene has a lower rim and an upper rim, each calixarene is (a) covalently bound through a metal atom to a porous oxide surface, (b) substituted with at least one polymerizable substituent, and (c) covalently bound through said at least one polymerizable substituent to a polymer strand 4 to 200 monomers in length which is also covalently bound to said at least one polymerizable substituent of a second calixarene in said plurality of calixarenes.

32. The composition of claim 31, wherein said metal atom through which each calixarene of said plurality of calixarenes is covalently bound to said porous oxide surface is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or iron atom.

33. The composition of claim 31, wherein said metal atom through which each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is a aluminum, titanium, or silicon atom.

34. The composition of claim 31, wherein said metal atom through which said each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is aluminum or titanium.

35. The composition of claim 31, wherein said metal atom through which said each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is titanium.

36. The composition of claim 31, wherein said porous oxide surface to which said plurality of calixarenes is covalently bound is silica, alumina, magnesium oxide, zirconia, aluminosilicate, or titania.

37. The composition of claim 31, wherein said porous oxide surface to which said plurality of calixarenes is covalently bound is silica.

38. The composition of claim 31, wherein said porous oxide surface to which said plurality of calixarenes is covalently bound is silica that has been heated to 800 ℃.

39. The composition of claim 31, further wherein said each calixarene of said plurality of calixarenes has a metal atom or a complex containing a metal atom substituted on said lower rim or on said upper rim.

40. The composition of claim 39, wherein said metal atom or said metal complex is substituted on said lower rim of said first calixarene is a metal atom and said metal atom is a titanium, aluminum, zirconium, hafnium, boron, gallium, or germanium atom.

41. The composition of claim 39, wherein said metal atom or said complex containing a metal atom is substituted on said lower rim of said first calixarene is a complex containing a metal atom and said metal atom is a titanium, aluminum, zirconium, hafnium, boron, gallium, or germanium atom.

42. The composition of claim 40, further wherein said metal atom through which each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is silicon.

43. The composition of claim 41, further wherein said metal atom through which each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is silicon.

44. The composition of claim 31, further wherein said each calixarene of said plurality of calixarenes has a titanium atom or a complex containing a titanium atom substituted on said lower rim or on said upper rim and said metal atom through which each calixarene in said plurality of calixarenes is covalently bound to said porous oxide surface is silicon.

45. The composition of claim 31, wherein said first polymerizable substituent of said first calixarene has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate, or a crosslinking variant of one of these.

46. The composition of claim 31, wherein said plurality of calixarenes is of material E of Scheme 6.

47. The composition of claim 31, wherein said plurality of calixarenes is of material 4-6 of Scheme 4.

48. The composition of claim 31, wherein said plurality of calixarenes is of material 11, 12a, or 12b of Scheme 3.

49. The composition of claim 31, wherein said plurality of calixarenes are calix[4]arenes.

50. The composition of claim 31, wherein said plurality of calixarenes are calix[6]arenes.

51. The composition of claim 31, wherein said plurality of calixarenes are calix[8]arenes.

52. The composition of claim 31, wherein said polymer strand is composed of divinyl benzene monomers.

53. The composition of claim 31, wherein said polymer strand is composed of monomers of 1,2-diisopropylbenzene, 1,3- diisopropylbenzene, 1,4-diisopropylbenzene, or a combination of any of two or all three of these.

54. A method for stabilizing a population of calixarenes, each covalently bound through a metal atom to a porous oxide surface, on said porous oxide surface, each calixarene having a lower rim and an upper rim, said method comprising: (a) providing a population of calixarenes, each having a hydroxyl group disposed on at least four carbon atoms on said lower rim of said calixarene, (b) covalently attaching a polymerizable substituent to a first hydroxyl group on a first carbon atom on said lower rim of each calixarene of said population, (c) covalently attaching to said porous oxide surface through a metal atom each calixarene of said population of calixarenes, and, (d) covalently attaching to said polymerizable substituent of each calixarene of said population of calixarenes a polymer strand of 4 to 200 in length, which polymerstrand is also covalently connected to a polymerizable substituent of a different calixarene of said population of calixarenes or to another polymer strand, thereby stabilizing said population of calixarenes on said porous oxide surface.

55. The method of claim 54, wherein said polymerizable substituent of step b has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate, or a crosslinking variant of one of these.

56. The method of claim 54, wherein said polymerizable substituent of step b has a functionality consisting of styrene.

57. The method of claim 54, wherein said metal atom through which each calixarene of said population of calixarenes is covalently bound to said porous oxide surface is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or iron atom.

58. The method of claim 54, wherein said metal atom through which each calixarene of said population of calixarenes is covalently bound to said porous oxide surface is a silicon, titanium, or aluminum, atom.

59. The method of claim 54, further wherein said upper rim or said lower rim of each of said population of calixarenes is substituted with a metal atom or a complex containing a metal atom.

60. The method of claim 59, wherein said metal atom substituted on said upper rim or said lower rim of each calixarene of said population of calixarenes is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or an iron atom.

61. The method of claim 60, wherein said metal atom of said complex containing a metal atom substituted on said upper rim or said lower rim of each calixarene of said population of calixarenes is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or an iron atom.

62. The method of claim 54, wherein said calixarenes are calix[4]arenes.

63. The method of claim 54, wherein said calixarenes are calix[6]arenes.

64. The method of claim 54, wherein said calixarenes are calix[8]arenes.

65. A method for stabilizing a population of calixarenes, each covalently bound through a metal atom to a porous oxide surface, on said porous oxide surface, each calixarene having a lower rim and an upper rim, said method comprising: (a) providing a population of calixarenes, each having a hydroxyl group disposed on at least four carbon atoms on said lower rim of said calixarene, (b) covalently attaching to said porous oxide surface through a metal atom each calixarene of said population of calixarenes, (c) covalently attaching a polymerizable substituent to a first hydroxyl group on a first carbon atom on said lower rim of each calixarene of said population, and, (d) covalently attaching to said polymerizable substituent of each calixarene of said population of calixarenes a polymer strand 4 to 200 monomers in length, and also covalently attaching said polymer strand to a polymerizable substituent of a different calixarene of said population of calixarenes or to another polymer strand, thereby stabilizing said population of calixarenes on said porous oxide surface.

66. The method of claim 65, wherein said polymerizable substituent of step b has a functionality consisting of styrene, acrylate, vinyl benzene, divinyl benzene, isopropyl benzene, diisopropyl benzene, or methacrylate, or a crosslinking variant of one of these.

67. The method of claim 65, wherein said polymerizable substituent of step b has a functionality consisting of styrene.

68. The method of claim 65, wherein said metal atom through which each calixarene of said population of calixarenes is covalently bound to said porous oxide surface is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or iron atom.

69. The method of claim 65, wherein said metal atom through which each calixarene of said population of calixarenes is covalently bound to said porous oxide surface is a silicon, titanium, or aluminum, atom.

70. The method of claim 65, further wherein said upper rim or said lower rim of each of said population of calixarenes is substituted with a metal atom or a complex containing a metal atom.

71. The method of claim 65, wherein said metal atom substituted on said upper rim or said lower rim of each calixarene of said population of calixarenes is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium,chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or an iron atom.

72. The method of claim 65, wherein said metal atom of said complex containing a metal atom substituted on said upper rim or said lower rim of each calixarene of said population of calixarenes is a silicon, titanium, aluminum, tungsten, niobium, zirconium, iron, manganese, vanadium, chromium, tantalum, phosphorus, boron, rhodium, molybdenum, germanium, copper, platinum or an iron atom.

73. The method of claim 65 wherein said calixarenes are calix[4]arenes.

74. The method of claim 65, wherein said calixarenes are calix[6]arenes.

75. The method of claim 65, wherein said calixarenes are calix[8]arenes.

76. A method for stabilizing a population of calixarenes, said comprising a method selected from: (A) steps a-d of Scheme 3, (B) steps a-d of Scheme 4, (C) steps i-iv of Scheme 5, or, (D) steps (a) through (d) of Scheme 4.

77. The method of claim 75, wherein said population of calixarenes is covalently attached to a porous inorganic oxide surface of silica, alumina, magnesium oxide, zirconia, aluminosilicate, or titania.

78. The method of claim 77, wherein said porous inorganic oxide surface is silica.

79. The method of claim 77, wherein said porous inorganic oxide surface is SiO2@800.

80. The method of claim 76, wherein said method is of (A) and said population of calixarenes is of material 11, 12a, or 12b, or a combination of 12a and 12b.

81. The method of claim 76, wherein said method is of (B) and said population of calixarenes is of material 4-6.

82. The method of claim 76, wherein said method is of (C) and said population of calixarenes is of material E.

83. A method of providing a plurality of calixarenes grafted to a porous oxide surface through a metal atom, wherein members of said plurality of calixarenes grafted to a porous oxide surface through a metal atom are connected to a network of covalently crosslinked polymer strands covalently attached to members of said plurality of calixarenes, said method comprising (a) obtaining a plurality of first calixarenes substituted with a first polymerizable substituent and grafted to a porous oxide surface through a metal atom,(b) contacting said first polymerizable substituent on said plurality of first calixarenes with a plurality of polymer-forming monomers, crosslinking monomers, crosslinking comonomers, or combination of two or more of these, under conditions allowing a first one of said polymer-forming monomers, crosslinking monomers, and crosslinking comonomers to covalently attach to said first polymerizable substituent on said plurality of said first calixarenes, and then to polymerize from said first one of said polymer-forming monomers, crosslinking monomers, crosslinking comonomers, or combination of two or more of these, until each first calixarene bears a first crosslinking polymer strand having a length of 4 to 200 monomers, which first crosslinking polymer strands is each covalently attached to a second polymerizable substituents, each of which second polymerizable substituents is covalently attached to a member of a second plurality of calixarenes, thereby providing a plurality of calixarenes grafted to a porous oxide surface through a metal atom, wherein members of said plurality of calixarenes grafted to a porous oxide surface through a metal atom are connected to a network of covalently crosslinked polymer strands.

84. The method of claim 83, wherein said metal atoms grafting said plurality of calixarenes to said porous oxide surface are titanium, aluminum, zirconium, hafnium, boron, gallium, germanium, Si(IV), or P(V) atoms.

85. The method of claim 83, wherein said metal atoms are aluminum or titanium atoms.

86. The method of claim 83, wherein said porous oxide surface is silica, alumina, magnesium oxide, zirconia, aluminosilicate, or titania.

87. The method of claim 83, wherein said porous oxide surface is silica.

88. The method of claim 83, wherein said porous oxide surface is SiO2@800.

89. The method of claim 83, wherein said crosslinking monomer is divinyl benzene.

90. The method of claim 83, wherein said crosslinking monomer is 1,2- diisopropylbenzene, 1,3- diisopropylbenzene, 1,4-diisopropylbenzene, or a combination of any of two or of all three of these.

91. The method of claim 83, wherein said length of said first crosslinking polymer is 4 to 100 monomers.

92. The method of claim 83, wherein said length of said first crosslinking polymer is 4 to 50 monomers.

93. The method of claim 83, wherein said length of said first crosslinking polymer is 10 to 20 monomers.

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