Method for preparing catechol styrene copolymer

Abstract

Poly (catechol-styrene) (PCS) is a novel material having a variety of industrial and biomedical uses. For example, PCS acts as a binder that acts in a humid or underwater environment, and thus can be used in biomedical applications. The present disclosure provides a method of forming a poly (catechol-styrene) polymer. The method includes the step of polymerizing 3, 4-diacetoxystyrene and styrene in an emulsion polymerization to form a poly (3, 4-diacetoxystyrene-co-styrene) polymer. The polymer has acetate groups deprotected from an alcohol, thereby forming a poly (catechol-styrene) polymer. The poly (catechol-styrene) polymer has improved strength at a higher molecular weight.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 481,245, filed January 24, 2023, which is incorporated herein by reference in its entirety. Background Art

[0003] Poly(catechol-styrene) (PCS) is a new material with diverse industrial and biomedical applications. For example, PCS acts as an adhesive that functions in wet or underwater environments and can be used in a range of applications. The challenge lies in producing PCS in an economically viable process. To incorporate catechol moieties into PCS, the catechol hydroxyl groups must be protected prior to polymerization. The free hydroxyl groups of catechol act as free radical scavengers and can have adverse effects on polymerization, such as crosslinking and unintended molecular weight.

[0004] Most known polystyrene processes (and styrene copolymers) use RAFT or solvent-based anionic polymerization methods. The challenge with these types of polymerizations is that they are slow and do not reach full conversion. Large-scale polystyrene processes (and styrene copolymers) are performed using solvent polymerization, but typically only produce monomer conversions of 90%. For most commercially available styrene copolymers, this degree of monomer conversion is not a problem. At the end of these processes, multiple stages of extraction / extrusion are used to bring the polymer above its melting point, volatilize any impurities, and extrude the pure polymer. The problem with applying these processes to PCS production is that PCS is sensitive to heat and oxygen (especially the two together). Therefore, it is critical for a commercially viable PCS production polymerization process to achieve monomer conversions close to 100%. Summary of the Invention

[0005] The present disclosure provides a method for forming a poly(catechol-styrene) polymer. The method includes the steps of polymerizing 3,4-diacetoxystyrene and styrene in an emulsion polymerization to form a poly(3,4-diacetoxystyrene-co-styrene) polymer. The polymer has acetate groups deprotected from an alcohol to form the poly(catechol-styrene) polymer. The poly(catechol-styrene) polymer has improved strength at higher molecular weights. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments and, together with the general description given above and the detailed description of the embodiments given below, serve to explain the principles of the disclosure.

[0007] Figure 1 is a graph of the molecular weight of the resulting polymer based on the amount of initiator used during polymerization; Example 3.

[0008] Figure 2 is a graph of the molecular weight of the resulting polymer based on the amount of chain transfer agent used during polymerization, Example 3.

[0009] Figure 3 is a table showing a comparison of the dry adhesion strength and molecular weight of poly(catechol-styrene) polymers prepared by methods using diacetoxy and methoxy protecting groups; Example 6.

[0010] Figure 4 is a table showing a comparison of the wet adhesion strength and molecular weight of poly(catechol-styrene) polymers prepared by methods using diacetoxy and methoxy protecting groups; Example 7. DETAILED DESCRIPTION

[0011] The present disclosure provides a scalable process for producing poly(catechol-styrene) using relatively inexpensive raw materials. Caffeic acid is naturally present in almost all plant species and is a readily available starting material. Caffeic acid can undergo a one-pot decarboxylation and hydroxyl protection to form a monomer containing catechol. The use of acid-labile protecting groups (such as acetate) allows the catechol moiety to be released after polymerization under inexpensive, mild conditions.

[0012] In some aspects, the present disclosure relates to a method of forming a poly(catechol-styrene) polymer, the method comprising the steps of:

[0013] (i) polymerizing 3,4-diacetoxystyrene and styrene to form a poly(3,4-diacetoxystyrene-co-styrene) polymer, and

[0014] (ii) deprotecting the acetate groups of the resulting poly(3,4-diacetoxystyrene-co-styrene) polymer to form a poly(catechol-styrene) polymer.

[0015] In some aspects, the present disclosure relates to a method of forming a poly(catechol-styrene) polymer, the method comprising the steps of:

[0016] (i) polymerizing 3,4-diacetoxystyrene and styrene in an emulsion polymerization to form a poly(3,4-diacetoxystyrene-co-styrene) polymer, and

[0017] (ii) deprotecting the acetate groups of the resulting poly(3,4-diacetoxystyrene-co-styrene) polymer to form a poly(catechol-styrene) polymer.

[0018] In some embodiments, 3,4-diacetoxystyrene (DAS) monomer is copolymerized with styrene monomer via an emulsion polymerization technique as shown in Scheme 1.

[0019] Plan I

[0020]

[0021] In some embodiments of the emulsion polymerization, the monomers polymerized are 3,4-diacetoxystyrene (DAS) monomer and styrene. Methods for preparing DAS are known in the art.

[0022] The ratio of 3,4-diacetoxystyrene (DAS) monomer to styrene monomer will affect the relative amounts of these moieties in the resulting poly(3,4-diacetoxystyrene-co-styrene) polymer and the final product poly(catechol-styrene) polymer. In some embodiments, the polymerization reaction additionally includes a monomer having a fatty acid chain such that the polymerization reaction produces a modified PCS.

[0023] In some embodiments, the weight ratio of styrene monomer to DAS monomer used in the polymerization reaction is between about 0.1 and about 5.0, such as, for example, about 0.1, about 0.11, about 0.12, about 0.13, about 0.14, about 0.15, about 0.16, about 0.17, about 0.18, about 0.19, about 0.20, about 0.21, about 0.22, about 0.23, about 0.24, about 0.25, about 0.26, about 0.27, about 0.28, about 0.29, about 0.30, about 0.31, about 0.32, about 0.33, about 0.34, about 0.35, about 0.36, about 0.37, about 0.38, about 0.39, about 0.40, about 0.41, about 0.42, about 0.43, about 0.44, about 0.45, about 0.46, about 0.47, about 0.48, about 0.49, about 0.50, about 0.51, about 0.52, about 0.53, about 0.54, about 0.55, about 0.56, about 0.57, about 0.58, about 0.59, about 0.60 about 0.35, about 0.36, about 0.37, about 0.38, about 0.39, about 0.40, about 0.41, about 0.42, about 0.43, about 0.44, about 0.45, about 0.46, about 0.47, about 0.48, about 0.49, about 0.50, about 0.51, about 0.52, about 0.53, about 0.54, about 0.55, about 0.56, about 0.57, about 0.58, about 0.59, about 0.60, about 0.61, about 0.62, about 0.63, about 0.64, about 0.65, about 0.66, about 0.67, about 0.68, about 0.69, about 0.70, about 0.71, about 0.72, about 0.73, about 0.74, about 0.75, about 0.76, about 0.77, about 0.78, about 0.79, about 0.80, about 0.81, about 0.82, about 0.83, about 0.84, about 0.85, about 0.86, about 0.87, about 0.88, about 0.89, about 0.90, about 0.91, about 0.92, about 0.93, about 0.94, about 0.95, about 0.96, about 0.97, about 0.98, about 0.99, about 1.0, about about 3.8, about 3.9, about 4.0, about 4.1, about 4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8, about 4.9, or about 5.0.

[0024] In some embodiments, the weight ratio of styrene monomer to DAS monomer used in the polymerization reaction is between about 1.1 and about 1.9, such as, for example, about 1.10, about 1.11, about 1.12, about 1.13, about 1.14, about 1.15, about 1.16, about 1.17, about 1.18, about 1.19, about 1.20, about 1.21, about 1.22, about 1.23, about 1.24, about 1.25, about 1.26, about 1.27, about 1.28, about 1.29, about 1.30, about 1.31, about 1.32, about 1.33, about 1.34, about 1.35, about 1.36, about 1.37, about 1.38, about 1.39, about 1.40, about 1.41, about 1.42, about 1.43, about 1.44, about 1.45, about 1 .46, about 1.47, about 1.48, about 1.49, about 1.50, about 1.51, about 1.52, about 1.53, about 1.54, about 1.55, about 1.56, about 1.57, about 1.58, about 1.59, about 1.60, about 1.61, about 1.62, about 1.63, about 1.64, about 1.65, about 1.66, about 1.67, about 1.6 8, about 1.69, about 1.70, about 1.71, about 1.72, about 1.73, about 1.74, about 1.75, about 1.76, about 1.77, about 1.78, about 1.79, about 1.80, about 1.81, about 1.82, about 1.83, about 1.84, about 1.85, about 1.86, about 1.87, about 1.88, about 1.89 or about 1.90.

[0025] In other embodiments, the weight ratio of styrene monomer to DAS monomer used in the polymerization reaction is between about 1.4 and about 1.5, such as, for example, about 1.40, about 1.41, about 1.42, about 1.43, about 1.44, about 1.45, about 1.46, about 1.47, about 1.48, about 1.49, or about 1.50.

[0026] In some embodiments of emulsion polymerization, the monomers are mixed with a surfactant, an initiator, and a chain transfer agent.

[0027] In some embodiments of emulsion polymerization, the monomers are mixed with a surfactant, such as, for example, an anionic surfactant, a cationic surfactant, a nonionic surfactant, or any combination thereof. In some embodiments of emulsion polymerization, the surfactant is sodium lauryl sulfate (i.e., sodium dodecyl sulfate), other sulfates, carboxylic acids (e.g., fatty acids), sulfonates, and phosphorus compounds. Other examples include alkyl alcohols, such as, for example, cetyl alcohol.

[0028] In some embodiments, the ratio of surfactant to total monomers, expressed as a percentage, is between about 0.2% and about 6.0%, such as, for example, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5. 7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, or about 6.0%. As used herein, percentages are calculated as (weight of surfactant) / (weight of DAS+weight of styrene)*100.

[0029] In some embodiments, the ratio of surfactant to total monomers, expressed as a percentage, is between about 0.8% and about 3.0%, such as, for example, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. In some embodiments, the ratio of sodium lauryl sulfate to total monomers, expressed as a percentage, is between about 1.2% and about 1.4%, such as, for example, about 1.20%, about 1.21%, about 1.22%, about 1.23%, about 1.24%, about 1.25%, about 1.26%, about 1.27%, about 1.28%, about 1.29%, about 1.30%, about 1.31%, about 1.32%, about 1.33%, about 1.34%, about 1.35%, about 1.36%, about 1.37%, about 1.38%, about 1.39%, or about 1.40%. As used herein, percentages are calculated as (weight of surfactant) / (weight of DAS+weight of styrene)*100.

[0030] In some embodiments, the surfactant is sodium lauryl sulfate (ie, sodium dodecyl sulfate).

[0031] In some embodiments, the ratio of sodium lauryl sulfate to total monomers, expressed as a percentage, is between about 0.2% and about 6.0%, such as, for example, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5. .7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9% or about 6.0%.

[0032] In some embodiments, the ratio of sodium lauryl sulfate to total monomers, expressed as a percentage, is between about 0.8% and about 3.0%, such as, for example, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. In some embodiments, the ratio of sodium lauryl sulfate to total monomers, expressed as a percentage, is between about 1.2% and about 1.4%, such as, for example, about 1.20%, about 1.21%, about 1.22%, about 1.23%, about 1.24%, about 1.25%, about 1.26%, about 1.27%, about 1.28%, about 1.29%, about 1.30%, about 1.31%, about 1.32%, about 1.33%, about 1.34%, about 1.35%, about 1.36%, about 1.37%, about 1.38%, about 1.39%, or about 1.40%. As used herein, percentages are calculated as (weight of SLS) / (weight of DAS+weight of styrene)*100.

[0033] In other embodiments, the surfactant is cetyl alcohol.

[0034] In some embodiments, the ratio of cetyl alcohol to total monomers, expressed as a percentage, is between about 0.5% and about 10.0%, such as, for example, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, about 7.0%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, about 8.0%, about 8.1%, about 8.2%, about 8.3%, about 8.4%, about 8.5%, about 8.6%, about 8.7%, about 8.8%, about 8.9%, about 9.0%, about 9.1%, about 9.2%, about 9.3%, about 9.4%, about 9.5%, about 9.6%, about 9.7%, about 9.8%, about 9.9% or about 10.0%.

[0035] In some embodiments, the ratio of cetyl alcohol to total monomers, expressed as a percentage, is between about 2.0% and about 7.0%, such as, for example, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, about 7.0%, about 7.1%, about 7. %, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9% or about 7.0%. In other embodiments, the ratio of cetyl alcohol to total monomers, expressed as a percentage, is between about 2.50% and about 3.40%, such as, for example, 2.50%, 2.51%, 2.52%, 2.53%, 2.54%, 2.55%, 2.56%, 2.57%, 2.58%, 2.59%, 2.60%, 2.61%, 2.62%, 2.63%, 2.64%, 2.65%, 2.66%, 2.67%, 2.68%, 2.69%, 2.70%, 2.71%, 2.72%, 2.73%, 2.74%, 2.75%, 2.76%, 2.77%, 2.78%, 2.79%, 2.80%, 2.81%, 2.82%, 2.83%, 2.84%, 2.85%, 2.86%, 2.87%, 2.88%, 2.89%, 2.90%, 2.91%, 2.92%, 2.93%, 2.94%, 2.95%, 2.96%, 2.97%, 2.98%, 2.99%, 2.90%, 2.91%, 2.92%, 2.93%, 2.94%, 2.95%, 2.96%, 2.97%, 2.98%, 2.99%, 2.90%, 2.91%, 2.92%, 2.93%, 2.94%, 2.95%, 2.96%, 2.97%, 2.98%, 2.99%, 2.90%, 2.91%, 2.9 1%, 2.92%, 2.93%, 2.94%, 2.95%, 2.96%, 2.97%, 2.98%, 2.99%, 3.00%, 3.01%, 3.02%, 3.03%, 3.04%, 3.05%, 3.06%, 3.07%, 3.08%, 3.09%, 3.10%, 3.11%, 3.12%, 3.13%, 3.14%, 3.15%, 3 3.18%, 3.19%, 3.20%, 3.21%, 3.22%, 3.23%, 3.24%, 3.25%, 3.26%, 3.27%, 3.28%, 3.29%, 3.30%, 3.31%, 3.32%, 3.33%, 3.34%, 3.35%, 3.36%, 3.37%, 3.38%, 3.39% or 3.40%. As used herein, percentages are calculated as (weight of cetyl alcohol) / (weight of DAS+weight of styrene)*100.

[0036] In other embodiments, the surfactant is a mixture of sodium lauryl sulfate and cetyl alcohol. In some embodiments, the weight ratio of cetyl alcohol to sodium lauryl sulfate is between about 2.0 and about 4.0, such as, for example, about 2.0, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, or about 4.0.

[0037] In other embodiments, the weight ratio of cetyl alcohol to sodium lauryl sulfate is between about 2.30 and about 2.80, such as, for example, about 2.30, about 2.31, about 2.32, about 2.33, about 2.34, about 2.35, about 2.36, about 2.37, about 2.38, about 2.39, about 2.40, about 2.41, about 2.42, about 2.43, about 2.44, about 2.45, about 2.46, about 2.47, about 2.48, about 2.49, about 2.50, about 2.51 , about 2.52, about 2.53, about 2.54, about 2.55, about 2.56, about 2.57, about 2.58, about 2.59, about 2.60, about 2.61, about 2.62, about 2.63, about 2.64, about 2.65, about 2.66, about 2.67, about 2.68, about 2.69, about 2.70, about 2.71, about 2.72, about 2.73, about 2.74, about 2.75, about 2.76, about 2.77, about 2.78, about 2.79 or about 2.80.

[0038] In some aspects of emulsion polymerization, the polymerization mixture includes an initiator, such as, for example, persulfates (eg, sodium persulfate, potassium persulfate, ammonium persulfate, other persulfates), benzoyl peroxide, t-butyl hydroperoxide, and other water-soluble free radical initiators.

[0039] In some embodiments, the ratio of initiator to total monomers, expressed as a percentage, is between about 0.1% and about 3.0%, such as, for example, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. As used herein, percentages are calculated as (weight of initiator) / (weight of DAS+weight of styrene)*100.

[0040] In some embodiments, the ratio of initiator to total monomers, expressed as a percentage, is between about 1.0% and about 3.0%, such as, for example, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. As used herein, percentages are calculated as (weight of initiator) / (weight of DAS+weight of styrene)*100.

[0041] In some embodiments, the ratio of initiator to total monomers, expressed as a percentage, is between about 1.2% and about 1.4%, such as, for example, about 1.20%, about 1.21%, about 1.22%, about 1.23%, about 1.24%, about 1.25%, about 1.26%, about 1.27%, about 1.28%, about 1.29%, about 1.30%, about 1.31%, about 1.32%, about 1.33%, about 1.34%, about 1.35%, about 1.36%, about 1.37%, about 1.38%, about 1.39%, or about 1.40%. As used herein, percentages are calculated as (weight of initiator) / (weight of DAS+weight of styrene)*100.

[0042] In some embodiments, the initiator is a water-soluble free radical initiator.

[0043] In some embodiments, the initiator is potassium persulfate.

[0044] In some embodiments, the initiator is sodium persulfate.

[0045] In some embodiments, the initiator is ammonium persulfate.

[0046] In some embodiments, the initiator is benzoyl peroxide.

[0047] In some embodiments, the initiator is tert-butyl hydroperoxide.

[0048] In some embodiments, the ratio of potassium persulfate to total monomers expressed as a percentage is between about 0.1% and about 3.0%, such as, for example, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.5%, about 0.6%, about

[0049] %, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. As used herein, percentages are calculated as (weight of potassium persulfate) / (weight of DAS+weight of styrene)*100.

[0050] In some embodiments, the ratio of potassium persulfate to total monomers, expressed as a percentage, is between about 1.0% and about 3.0%, such as, for example, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3.0%. As used herein, percentages are calculated as (weight of potassium persulfate) / (weight of DAS+weight of styrene)*100.

[0051] In some embodiments, the ratio of potassium persulfate to total monomers, expressed as a percentage, is between about 1.2% and about 1.4%, such as, for example, about 1.20%, about 1.21%, about 1.22%, about 1.23%, about 1.24%, about 1.25%, about 1.26%, about 1.27%, about 1.28%, about 1.29%, about 1.30%, about 1.31%, about 1.32%, about 1.33%, about 1.34%, about 1.35%, about 1.36%, about 1.37%, about 1.38%, about 1.39%, or about 1.40%. As used herein, percentages are calculated as (weight of potassium persulfate) / (weight of DAS+weight of styrene)*100.

[0052] In some aspects of emulsion polymerization, the polymerization mixture includes a chain transfer agent such as, for example, dodecyl mercaptan (also known as lauryl mercaptan or n-dodecyl mercaptan), carbon tetrachloride, or a halogenated hydrocarbon. The amount of chain transfer agent used will vary the molecular weight of the polymer.

[0053] In some embodiments, the ratio of chain transfer agent to total monomer, expressed as a percentage, is between about 0.05% and about 10%, such as, for example, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.10%, about 0.11%, about 0.12%, about 0.13%, about 0.14%, about 0.15%, about 0.16%, about 0.17%, about 0.18%, about 0.19%, about 0.20%, about 0.21%, about 0.22%, about 0.23%, about 0.24%, about 0.25%, about 0.26%, about 0.27%, about 0.28%, about 0.29%, about 0.30%, about 0.31%, about 0.32%, about 0.33%, , about 0.34%, about 0.35%, about 0.36%, about 0.37%, about 0.38%, about 0.39%, about 0.40%, about 0.41%, about 0.42%, about 0.43%, about 0.4%, about 0.45%, about 0.46%, about 0.47%, about 0.48%, about 0.49%, about 0.50%, about 0.51%, about 0.52%, about 0.53%, about 0.54%, about 0.55%, about 0.56%, about 0.57%, about 0.58%, about 0.59%, about 0.60%, about 0.61%, about 0.62%, about 0.63%, about 0.64%, about 0.65%, about 0.66%, about 0.67%, about 0.68%, about 0.69%, about 100%, about 101%, about 102%, about 103%, about 104%, about 105%, about 106%, about 107%, about 108%, about 109%, about 110%, about 111%, about 112%, about 113%, about 114%, about 115%, about 116%, about 117%, about 118%, about 119%, about 120%, about 121%, about 122%, about 123%, about 124%, about 125%, about 126%, about 127%, about 128%, about 129%, about 130%, about 131%, about 132%, about 133%, about 134%, about 9%, about 0.70%, about 0.71%, about 0.72%, about 0.73%, about 0.74%, about 0.75%, about 0.76%, about 0.77%, about 0.78%, about 0.79%, about 0.80%, about 0.81%, about 0.82%, about 0.83%, about 0.84%, about 0.85%, about 0.86%, about 0.87%, about 0.88%, about 0.89%, about 0.90%, about 0.91%, about 0.92%, about 0.93%, about 0.94%, about 0.95%, about 0.96%, about 0.97%, about 0.98%, about 0.99%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, About 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, about 7.0%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, about7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, about 7.0%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, about 8.0%, about 8.1%, about 8.2%, about 8.3%, about 8.4%, about 8.5%, about 8.6%, about 8.7%, about 8.8%, about 8.9%, about 9.0%, about 9.1%, about 9.2%, about 9.3%, about 9.4%, about 9.5%, about 9.6%, about 9.7%, about 9.8%, about 9.9%, or about 10.0%. As used herein, percentages are calculated as (weight of chain transfer agent) / (weight of DAS+weight of styrene)*100.

[0054] In some embodiments, the ratio of chain transfer agent to total monomers, expressed as a percentage, is between about 0.1% and about 0.8%, such as, for example, about 0.10%, about 0.11%, about 0.12%, about 0.13%, about 0.14%, about 0.15%, about 0.16%, about 0.17%, about 0.18%, about 0.19%, about 0.20%, about 0.21%, about 0.22%, about 0.23%, about 0.24%, about 0.25%, about 0.26%, about 0.27%, about 0.28%, about 0.29%, about 0.30%, about 0.31%, about 0.32%, about 0.33%, about 0.34%, about 0.35%, about 0.36%, about 0.37%, about 0.38%, about 0.39%, about 0.40%, about 0.41%, about 0.42%, about 0.43%, about 0.4%, about 0.45%, about 0.46%, about 0.47%, about 0.48%, about 0.49%, about 0.50%, about 0.51%, about 0.52%, about 0.53%, about 0.54%, about 0.55%, about 0.56%, about 0.57%, about 0.58%, about 0.59%, about 0.60%, about 0.61%, about 0.62%, about 0.63%, about 0.64%, about 0.65%, about 0.66%, about 0.67%, about 0.68%, 88%, about 0.89%, or about 0.90%. As used herein, percentages are calculated as (weight of chain transfer agent) / (weight of DAS+weight of styrene)*100.

[0055] In some embodiments, the chain transfer agent is dodecyl mercaptan.

[0056] In some embodiments, the chain transfer agent is carbon tetrachloride.

[0057] In some embodiments, the chain transfer agent is a halogenated hydrocarbon.

[0058] In some embodiments, the ratio of dodecyl mercaptan to total monomers, expressed as a percentage, is between about 0.05% and about 10%, such as, for example, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.10%, about 0.11%, about 0.12%, about 0.13%, about 0.14%, about 0.15%, about 0.16%, about 0.17%, about 0.18%, about 0.19%, about 0.20%, about 0.21%, about 0.22%, about 0.23%, about 0.24%, about 0.25%, about 0.26%, about 0.27%, about 0.28%, about 0.29%, about 0.30%, about 0.31%, about 0.32%, about 0.33%, about 0.34%, about 0.36%, about 0.37%, about 0.38%, about 0.39%, about 0.40%, about 0.41%, about 0.42%, about 0.43%, about 0.44%, about 0.45%, about 0.46%, about 0.47%, about 0.48%, about 0.49%, about 0.50%, about 0.51%, about 0.52%, about 0.53%, about 0.54%, about 0.55%, about 0.56%, about 0.57%, about 0.58%, about 0.59%, about 0.60%, about 0.61%, about 0.62%, about 0.63%, about 0.64%, about 0.65%, about 0.66%, about 0.67%, about 0.68%, about 0.69%, about 0.70%, about 0.71%, about 0.7 3%, about 0.34%, about 0.35%, about 0.36%, about 0.37%, about 0.38%, about 0.39%, about 0.40%, about 0.41%, about 0.42%, about 0.43%, about 0.4%, about 0.45%, about 0.46%, about 0.47%, about 0.48%, about 0.49%, about 0.50%, about 0.51%, about 0.52%, about 0.53%, about 0.54%, about 0.55%, about 0.56%, about 0.57%, about 0.58%, about 0.59%, about 0.60%, about 0.61%, about 0.62%, about 0.63%, about 0.64%, about 0.65%, about 0.66%, about 0.67%, about 0.68%, about 0. 69%, about 0.70%, about 0.71%, about 0.72%, about 0.73%, about 0.74%, about 0.75%, about 0.76%, about 0.77%, about 0.78%, about 0.79%, about 0.80%, about 0.81%, about 0.82%, about 0.83%, about 0.84%, about 0.85%, about 0.86%, about 0.87%, about 0.88%, about 0.89%, about 0.90%, about 0.91%, about 0.92%, about 0.93%, about 0.94%, about 0.95%, about 0.96%, about 0.97%, about 0.98%, about 0.99%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5% , about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, about 7.0%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, about 8.0%, about 8.1%, about 8.2%, about 8.3%, about 8.4%, about 8.5%, about 8.6%, about 8.7%, about 8.8%, about 8.9%, about 9.0%, about 9.1%, about 9.2%, about 9.3%, about 9.4%, about 9.5%, about 9.6%, about 9.7%, about 9.8%, about 9.9%, or about 10.0%. As used herein, percentages are calculated as (weight of dodecyl mercaptan) / (weight of DAS+weight of styrene)*100.

[0059] In some embodiments, the ratio of dodecyl mercaptan to total monomers, expressed as a percentage, is between about 0.1% and about 0.8%, such as, for example, about 0.10%, about 0.11%, about 0.12%, about 0.13%, about 0.14%, about 0.15%, about 0.16%, about 0.17%, about 0.18%, about 0.19%, about 0.20%, about 0.21%, about 0.22%, about 0.23%, about 0.24%. , about 0.25%, about 0.26%, about 0.27%, about 0.28%, about 0.29%, about 0.30%, about 0.31%, about 0.32%, about 0.33%, about 0.34%, about 0.35%, about 0.36%, about 0.37%, about 0.38%, about 0.39%, about 0.40%, about 0.41%, about 0.42%, about 0.43%, about 0.4%, about 0.45%, about 0.46%, About 0.47%, about 0.48%, about 0.49%, about 0.50%, about 0.51%, about 0.52%, about 0.53%, about 0.54%, about 0.55%, about 0.56%, about 0.57%, about 0.58%, about 0.59%, about 0.60%, about 0.61%, about 0.62%, about 0.63%, about 0.64%, about 0.65%, about 0.66%, about 0.67%, about 0.68%, 88%, about 0.89%, or about 0.90%. As used herein, percentages are calculated as (weight of dodecyl mercaptan) / (weight of DAS+weight of styrene)*100.

[0060] In some embodiments, the polymerization reaction further comprises a buffer, such as, for example, sodium bicarbonate.

[0061] In some embodiments, the polymerization reaction is an emulsion polymerization. Therefore, the solvent used for emulsion polymerization includes an aqueous solvent, such as water. A surfactant and, optionally, a salt, are used to form the emulsion. An initiator, such as potassium persulfate, initiates the polymerization reaction. In some embodiments, the reaction is carried out at an elevated temperature, such as between 65° C. and the boiling point of the solvent.

[0062] In some embodiments, 3,4-diacetoxystyrene (DAS) is copolymerized with styrene via emulsion polymerization. Styrene and 3,4-diacetoxystyrene (DAS) are blended together in a desired ratio with a chain transfer agent to produce a monomer blend. In some embodiments, varying the amount of chain transfer agent can control the molecular weight of the polymer.

[0063] The monomer blend is then added to a stirred aqueous solution of surfactant, chain initiator, and buffer at elevated temperature in an inert atmosphere to produce an emulsion polymerization reaction mixture.

[0064] In some aspects, the amount of water used in the emulsion polymerization is from about 190 grams to about 320 grams of total monomer per liter of water, such as, for example, about 190 grams, 195 grams, 200 grams, 205 grams, 210 grams, 215 grams, 220 grams, 225 grams, 230 grams, 235 grams, 240 grams, 245 grams, 250 grams, 255 grams, 260 grams, 265 grams, 270 grams, 275 grams, 280 grams, 285 grams, 290 grams, 295 grams, 300 grams, 305 grams, 310 grams, 315 grams, or 320 grams of total monomer per liter of water, depending on the total monomer used in the reaction.

[0065] In some embodiments, the elevated temperature is from about 40°C to about 100°C, such as, for example, about 40°C, about 41°C, about 42°C, about 43°C, about 44°C, about 45°C, about 46°C, about 47°C, about 48°C, about 49°C, about 50°C, about 51°C, about 52°C, about 53°C, about 54°C, about 55°C, about 56°C, about 57°C, about 58°C, about 59°C, about 60°C, about 61°C, about 62°C, about 63°C, about 64°C, about 65°C, about 66°C, about 67°C , about 68° C., about 69° C., about 70° C., about 71° C., about 72° C., about 73° C., about 74° C., about 75° C., about 76° C., about 77° C., about 78° C., about 79° C., about 80° C., about 81° C., about 82° C., about 83° C., about 84° C., about 85° C., about 86° C., about 87° C., about 88° C., about 89° C., about 90° C., about 91° C., about 92° C., about 93° C., about 94° C., about 95° C., about 96° C., about 97° C., about 98° C., about 99° C., or about 100° C. In some embodiments, the elevated temperature is about 70° C.

[0066] In some embodiments, the inert atmosphere for the emulsion polymerization reaction mixture is argon. In other embodiments, the inert atmosphere is nitrogen.

[0067] In some embodiments, the emulsion polymerization reaction mixture is stirred at an elevated temperature for about 3 hours to 8 hours, such as, for example, a time period of about 3 hours, about 3.5 hours, about 4 hours, about 4.5 hours, about 5 hours, about 5.5 hours, about 6 hours, about 6.5 hours, about 7 hours, about 7.5 hours, or about 8 hours. In some embodiments, the emulsion polymerization reaction mixture is stirred at an elevated temperature for about 4 hours. In other embodiments, the emulsion polymerization reaction mixture is stirred at an elevated temperature for about 6 hours.

[0068] In some embodiments, 3,4-diacetoxystyrene (DAS) is copolymerized with styrene via emulsion polymerization. In such embodiments, styrene and 3,4-diacetoxystyrene (DAS) are blended together in the desired ratio with a chain transfer agent, such as n-dodecyl mercaptan, to produce a monomer blend. Varying the amount of chain transfer agent can manipulate and control the molecular weight of the polymer. This monomer blend is added to a stirred aqueous solution of sodium lauryl sulfate, cetyl alcohol, potassium persulfate, and sodium bicarbonate at 65°C under argon to produce an emulsion polymerization reaction mixture. After four hours, the emulsion polymerization reaction mixture is cooled to room temperature, precipitated into a saline solution, and filtered to produce the protected polymer, poly(3,4-diacetoxystyrene-co-styrene).

[0069] In other embodiments, 3,4-diacetoxystyrene (DAS) is copolymerized with styrene via emulsion polymerization, wherein styrene and 3,4-diacetoxystyrene (DAS) are blended together in a desired ratio with a chain transfer agent, such as n-dodecyl mercaptan, to produce a monomer blend. Varying the amount of chain transfer agent can manipulate and control the molecular weight of the polymer. This monomer blend is added to a stirred aqueous solution of sodium lauryl sulfate, cetyl alcohol, potassium persulfate, and sodium bicarbonate at 70°C under nitrogen to produce an emulsion polymerization reaction mixture. After six hours, the emulsion polymerization reaction mixture is cooled, and the precipitated protected polymer, poly(3,4-diacetoxystyrene-co-styrene), is collected by centrifugation.

[0070] In some embodiments, the polymerization is anionic. The polymerization is carried out in an organic solvent. DAS and styrene are blended and dissolved in a solvent such as tetrahydrofuran or cyclohexane. Under an inert atmosphere such as nitrogen or argon, a free radical initiator such as sec-butyllithium or n-butyllithium is added to the polymerization solution. The reaction solution is maintained at a temperature between -78°C and 25°C with constant stirring.

[0071] In some embodiments, after the polymerization reaction, the poly(3,4-diacetoxystyrene-co-styrene) polymer is isolated from the polymerization reaction mixture.

[0072] In some embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer is isolated from the polymerization reaction mixture by precipitation and filtration.

[0073] In some embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer may be precipitated by cooling the polymerization reaction mixture.

[0074] In other embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer may be precipitated by mixing the polymerization reaction mixture with a salt solution.

[0075] In other embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer may be precipitated by cooling the polymerization reaction mixture and mixing with a salt solution. The precipitated polymer is then filtered and washed with a solvent such as water.

[0076] In other embodiments, an acid (such as HCl) is added to the emulsion to break the emulsion, which results in precipitation of the poly(3,4-diacetoxystyrene-co-styrene), which is then isolated by filtration. Such embodiments are advantageous because they require less water to precipitate the poly(3,4-diacetoxystyrene-co-styrene). Furthermore, the acid added to break the emulsion does not deprotect the poly(3,4-diacetoxystyrene-co-styrene).

[0077] In other embodiments, the poly(3,4-diacetoxystyrene-co-styrene) polymer may be precipitated by cooling the polymerization reaction mixture and then transferring the mixture to a centrifuge where the water is removed to yield a protected polymer powder.

[0078] In some aspects, the poly(3,4-diacetoxystyrene-co-styrene) polymers produced by the methods of the present disclosure have a molecular weight in the range of about 25,000 to about 1,100,000. In some aspects, the poly(3,4-diacetoxystyrene-co-styrene) polymers produced by the methods of the present disclosure have a molecular weight in the range of about 25,000 to about 300,000, such as, for example, 25,000, 50,000, 75,000, 100,000, 125,000, 150,000, 175,000, 200,000, 225,000, 250,000, 275,000, or 300,000.

[0079] In some aspects, the poly(3,4-diacetoxystyrene-co-styrene) polymers produced by the methods of the present disclosure have a polydispersity index (PDI) of about 2 to about 30, such as, for example, about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30. As used herein, the term polydispersity index refers to the ratio of the weight average molecular weight to the number average molecular weight. In some aspects, the poly(3,4-diacetoxystyrene-co-styrene) polymers produced by the methods of the present disclosure have a polydispersity index (PDI) of about 2 to about 4, such as, for example, about 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, or 4.

[0080] In some aspects, the emulsion polymerization reaction results in at least 95% conversion of the monomers (DAS and styrene) to polymer, such as, for example, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or at least 99.8% conversion of the monomers (DAS and styrene) to polymer. The degree of polymer conversion can be determined by methods known to those skilled in the art, including, for example, NMR, FTIR, or liquid chromatography.

[0081] Deprotection

[0082] In some aspects of the methods of the present disclosure, a poly(3,4-diacetoxystyrene-co-styrene) polymer is deprotected to yield poly(catechol-styrene) (PCS), as shown in Scheme 2 below. This deprotection is achieved by subjecting the poly(3,4-diacetoxystyrene-co-styrene) polymer to conditions that cleave the acetate. Such conditions include, for example, treatment with an aqueous acid such as hydrochloric acid (HCl), p-toluenesulfonic acid (p-TsOH), fluoroboric acid (HBF4), and camphorsulfonic acid (CSA), or treatment with an aqueous base such as NaOH, KOH, NH3, and methylamine (CH3NH2).

[0083] Option 2 :

[0084]

[0085] In some aspects of the disclosed methods, poly(3,4-diacetoxystyrene-co-styrene) polymer is deprotected using an acid to yield poly(catechol-styrene) (PCS), as shown in Scheme 3.

[0086] Option 3

[0087]

[0088] In some embodiments, the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with an acid. In some embodiments, the acid is selected from hydrochloric acid (HCl), p-toluenesulfonic acid (p-TsOH), fluoroboric acid (HBF4), camphorsulfonic acid (CSA), and nitric acid, and combinations thereof. In some embodiments, the acid is HCl.

[0089] In some embodiments, the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with an acid in an amount of 0.9 mmol to 1.9 mmol of acid per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer, such as, for example, 0.9 mmol, 0.91 mmol, 0.92 mmol, 0.93 mmol, 0.94 mmol, 0.95 mmol, 0.96 mmol, 0.97 mmol, 0.98 mmol, 0.99 mmol, 1.0 mmol, 1.01 mmol, 1.02 mmol, 1.03 mmol per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer. ,1.04mmol, 1.05mmol, 1.06mmol, 1.07mmol, 1.08mmol, 1.09mmol, 1.1mmol, 1.11mmol, 1.12mmol, 1.13mmol, 1.14mmol, 1.15mmol, 1.16mmol, 1.17mmol ,1.18mmol, 1.19mmol, 1.2mmol, 1.21mmol, 1.22mmol, 1.23mmol, 1.24mmol, 1.25mmol, 1.26mmol, 1.27mmol, 1.28mmol, 1.29mmol, 1.3mmol, 1.31mmol, 1.32mmol, 1.33mmol, 1.34mmol, 1.35mmol, 1.36mmol, 1.37mmol, 1.38mmol, 1.39mmol, 1.4mmol, 1.41mmol, 1.42mmol, 1.43mmol, 1.44mmol, 1.45mmol, 1.46mmol, 1.47mmol, 1.48mmol, 1.49mmol, 1.5mmol, 1.51mmol, 1.52mmol, 1.53mmol, 1.54mmol, 1.55mmol, 1.56mmol, 1.57mmol, 1.58mmol, 1.59mmol, 1.6mmol, 1.61mmol, 1.62mmol, 1.63mmol, 1.64mmol, 1.65mmol, 1.66mmol, 1.67mmol, 1.68mmol, 1.69mmol, 1.7mmol, 1.71mmol, 1.72mmol, 1.73mmol, 1 .74mmol, 1.75mmol, 1.76mmol, 1.77mmol, 1.78mmol, 1.79mmol, 1.8mmol, 1.81mmol, 1.82mmol, 1.83mmol, 1.84mmol, 1.85mmol, 1.86mmol, 1.87mmol, 1.88mmol, 1.89mmol or 1.9mmol of acid.

[0090] In some embodiments, the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with an acid in an amount of 1.4 to 1.5 mmol of acid per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer, such as, for example, 1.4 mmol, 1.41 mmol, 1.42 mmol, 1.43 mmol, 1.44 mmol, 1.45 mmol, 1.46 mmol, 1.47 mmol, 1.48 mmol, 1.49 mmol, or 1.5 mmol of acid per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer.

[0091] In some embodiments, the acid is prepared as a 1M-8M solution, such as, for example, 1M, 1.1M, 1.2M, 1.3M, 1.4M, 1.5M, 1.6M, 1.7M, 1.8M, 1.9M, 2M, 2.1M, 2.2M, 2.3M, 2.4M, 2.5M, 2.6M, 2.7M, 2.8M, 2.9M, 3M, 3.1M, 3.2M, 3.3M, 3.4M, 3.5M, 3.6M, 3.7M, 3.8M, 3.9M, 4M, 4.1M, 4.2M, 4.3M, 4.4 M, 7.4M, 7.5M, 7.6M, 7.7M, 7.8M, 7.9M, or 8M acid solution is added to the deprotection reaction.

[0092] In some embodiments, the acid is added to the deprotection reaction as a 4M-8M solution, such as, for example, a 4M, 4.1M, 4.2M, 4.3M, 4.4M, 4.5M, 4.6M, 4.7M, 4.8M, 4.9M, 5M, 5.1M, 5.2M, 5.3M, 5.4M, 5.5M, 5.6M, 5.7M, 5.8M, 5.9M, 6M, 6.1M, 6.2M, 6.3M, 6.4M, 6.5M, 6.6M, 6.7M, 6.8M, 6.9M, 7M, 7.1M, 7.2M, 7.3M, 7.4M, 7.5M, 7.6M, 7.7M, 7.8M, 7.9M, or 8M acid solution.

[0093] In some embodiments, the deprotection reaction is carried out by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with hydrochloric acid (HCl). In some embodiments, the HCl is in a 1M-8M solution, such as, for example, 1M, 1.1M, 1.2M, 1.3M, 1.4M, 1.5M, 1.6M, 1.7M, 1.8M, 1.9M, 2M, 2.1M, 2.2M, 2.3M, 2.4M, 2.5M, 2.6M, 2.7M, 2.8M, 2.9M, 3M, 3.1M, 3.2M, 3.3M, 3.4M, 3.5M, 3.6M, 3.7M, 3.8M, 3.9M, 4M, 4.1M, 4.2M, 4.3M, 4. 7M, 7.8M, 7.9M, 7.1M, 7.2M, 7.3M, 7.4M, 7.5M, 7.6M, 7.7M, 7.8M, 7.9M or 8M acid solution is added to the deprotection reaction.

[0094] In other embodiments, HCl is added to the deprotection reaction as a 4-8 M solution, such as, for example, a 4 M, 4.1 M, 4.2 M, 4.3 M, 4.4 M, 4.5 M, 4.6 M, 4.7 M, 4.8 M, 4.9 M, 5 M, 5.1 M, 5.2 M, 5.3 M, 5.4 M, 5.5 M, 5.6 M, 5.7 M, 5.8 M, 5.9 M, 6 M, 6.1 M, 6.2 M, 6.3 M, 6.4 M, 6.5 M, 6.6 M, 6.7 M, 6.8 M, 6.9 M, 7 M, 7.1 M, 7.2 M, 7.3 M, 7.4 M, 7.5 M, 7.6 M, 7.7 M, 7.8 M, 7.9 M, or 8 M HCl solution.

[0095] In some embodiments, the deprotection reaction is performed by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with 6M HCl.

[0096] In some aspects of the deprotection reaction, the poly(3,4-diacetoxystyrene-co-styrene) polymer is dissolved in a solvent such as, for example, THF, acetone, or dimethylformamide (DMF). In some embodiments of the deprotection reaction, the solvent is THF. In some embodiments of the deprotection reaction, the solvent is acetone. In other embodiments of the deprotection reaction, the solvent is dimethylformamide (DMF).

[0097] In some aspects of the deprotection reaction, the poly(3,4-diacetoxystyrene-co-styrene) polymer is dissolved in a solvent at a concentration of 280 to 500 grams of poly(3,4-diacetoxystyrene-co-styrene) polymer per liter of solvent.

[0098] In some embodiments of the deprotection reaction, the poly(3,4-diacetoxystyrene-co-styrene) polymer is prepared at a concentration of 280 to 345 grams of poly(3,4-diacetoxystyrene-co-styrene) polymer per liter of solvent, such as, for example, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345 gram, 308 g, 309 g, 310 g, 311 g, 312 g, 313 g, 314 g, 315 g, 316 g, 317 g, 318 g, 319 g, 320 g, 321 g, 322 g, 323 g, 324 g, 325 g, 326 g, 327 g, 328 g, 329 g, 330 g, 331 g, 332 g, 333 g, 334 g, 335 g, 336 g, 337 g, 338 g, 339 g, 340 g, 341 g, 342 g, 343 g, 344 g or 345 g of poly(3,4-diacetoxystyrene-co-styrene) polymer is dissolved in the solvent.

[0099] In some aspects of the deprotection reaction, the reaction mixture is heated to an elevated temperature, such as, for example, about 40°C to about 100°C, such as, for example, about 40°C, about 41°C, about 42°C, about 43°C, about 44°C, about 45°C, about 46°C, about 47°C, about 48°C, about 49°C, about 50°C, about 51°C, about 52°C, about 53°C, about 54°C, about 55°C, about 56°C, about 57°C, about 58°C, about 59°C, about 60°C, about 61°C, about 62°C, about 63°C, about 64°C, about 65°C, about ℃, about 66 ℃, about 67 ℃, about 68 ℃, about 69 ℃, about 70 ℃, about 71 ℃, about 72 ℃, about 73 ℃, about 74 ℃, about 75 ℃, about 76 ℃, about 77 ℃, about 78 ℃, about 79 ℃, about 80 ℃, about 81 ℃, about 82 ℃, about 83 ℃, about 84 ℃, about 85 ℃, about 86 ℃, about 87 ℃, about 88 ℃, about 89 ℃, about 90 ℃, about 91 ℃, about 92 ℃, about 93 ℃, about 94 ℃, about 95 ℃, about 96 ℃, about 97 ℃, about 98 ℃, about 99 ℃ or about 100 ℃.

[0100] In some embodiments of the deprotection reaction, the reaction mixture is heated to about 70°C.

[0101] In other embodiments of the deprotection reaction, the reaction mixture is heated to the reflux temperature of the solvent.

[0102] In some aspects, the deprotection reaction is carried out for up to 48 hours, such as for example 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 25 hours, 26 hours, 27 hours, 28 hours, 29 hours, 30 hours, 31 hours, 32 hours, 33 hours, 34 hours, 35 hours, 36 hours, 37 hours, 38 hours, 39 hours, 40 hours, 41 hours, 42 hours, 43 hours, 44 hours, 45 hours, 46 hours, 47 hours or 48 hours. In some embodiments, the deprotection reaction is carried out for 24 hours. In some embodiments, the deprotection reaction is carried out for 48 hours.

[0103] In some embodiments, after deprotection, the reaction mixture is neutralized with a base such as sodium bicarbonate.

[0104] In some aspects of the present disclosure, the deprotection reaction results in at least 90% deprotection, e.g., at least 90% deprotection, at least 91% deprotection, at least 92% deprotection, at least 93% deprotection, at least 94% deprotection, at least 95% deprotection, at least 96% deprotection, at least 97% deprotection, at least 98% deprotection, at least 99% deprotection, or 100% deprotection. As used herein, % deprotection refers to the percentage of acetoxy-protected catechol hydroxyl groups in the PCS polymer that have been converted to catechol hydroxyl groups (i.e., deprotected catechol hydroxyl groups). % deprotection can be measured by standard techniques, such as, for example, by NMR.

[0105] In some embodiments, the deprotection reaction results in at least 95% deprotection.

[0106] In some embodiments, the deprotected product poly(catechol-styrene) polymer is isolated by precipitation and filtration. For example, in some embodiments, the poly(catechol-styrene) polymer is precipitated by cooling the deprotection reaction mixture to about 25° C. to 35° C. and then adding a solvent (i.e., an antisolvent) such as water to the reaction mixture. In other embodiments, the poly(catechol-styrene) polymer is precipitated by cooling the deprotection reaction mixture to about 25° C. to 35° C. and then adding the reaction mixture to an antisolvent such as water.

[0107] In some embodiments, the poly(catechol-styrene) polymer is precipitated by cooling the deprotection reaction mixture to about 25° C. to 35° C. and then adding the reaction mixture to water. In some embodiments, the poly(catechol-styrene) polymer is precipitated by cooling the deprotection reaction mixture to about 25° C. to 35° C. and then adding the reaction mixture to deionized water.

[0108] After precipitation, the precipitate can then be collected by filtration.

[0109] In some embodiments, the poly(catechol-styrene) polymer precipitate is redissolved in a solvent, such as a polar solvent. Examples of polar solvents include acetone, dichloromethane, methyl ethyl ketone, and DMF. The poly(catechol-styrene) polymer can then be precipitated by adding a non-polar solvent, such as hexane or diethyl ether. In some embodiments, the poly(catechol-styrene) polymer can be redissolved a third time and isolated by removing the solvent by evaporation.

[0110] In other embodiments, the poly(catechol-styrene) polymer precipitate is dissolved in a solvent such as, for example, acetone or THF. The resulting solution is then added portionwise to water to precipitate the poly(catechol-styrene) polymer. This procedure—dissolving in a solvent and then adding the resulting solution portionwise to water—can be repeated any number of times.

[0111] In other embodiments, the poly(catechol-styrene) polymer precipitate is dissolved in a solvent such as, for example, acetone or THF. The resulting solution is then added portionwise to an antisolvent such as hexane to precipitate the poly(catechol-styrene) polymer. This procedure—dissolving in a solvent and then adding the resulting solution portionwise to the antisolvent—can be repeated any number of times.

[0112] In some embodiments, the solvent is removed by evaporation and the poly(catechol-styrene) polymer is dissolved in a polar solvent such as acetone. The acetone solution can be evaporated to obtain a solid poly(catechol-styrene) polymer, or the acetone solution can be spray dried to obtain a solid poly(catechol-styrene) polymer.

[0113] The deprotection and separation steps can be challenging because the viscous, partially solvated, precipitated poly(catechol-styrene) polymer is difficult to handle and can pose challenges for automated production, thus currently relying on extensive manual manipulation.

[0114] In some embodiments, the protected polymer poly(3,4-diacetoxystyrene-co-styrene) is dissolved in tetrahydrofuran (THF) at 45°C. Upon complete dissolution, 6 molar hydrochloric acid (HCl) is added, and the reaction is refluxed at 70°C overnight. The next day, the reaction is cooled to room temperature and precipitated into stirred water. The water is decanted, and the polymer is dissolved in acetone and precipitated in portions into stirred hexane. The hexane is decanted, and the polymer is collected and dried in a vacuum oven.

[0115] In other embodiments, deprotection is performed by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with a base such as potassium hydroxide. The reaction mixture is neutralized and the product is isolated by precipitation and redissolution as previously described.

[0116] In some embodiments, the polymerization and deprotection synthesis steps are carried out in the same reaction vessel without isolating the intermediate protected polymer. The resulting poly(catechol-styrene) polymer can be emulsified and spray dried or solidified, such as by adding a salt. The solidified poly(catechol-styrene) polymer can be purified by washing with a solvent such as water.

[0117] In some embodiments, the poly(catechol-styrene) produced by this method has a molecular weight in the range of 15,000 to 1,000,000, such as 15,000 to 188,000, as measured by GPC.

[0118] In other embodiments, the poly(catechol-styrene) produced by the methods of the present disclosure has a molecular weight of about 50,000 to about 400,000, such as, for example, about 50,000, 75,000, 100,000, 125,000, 150,000, 175,000, 200,000, 225,000, 250,000, 275,000, 300,000, 325,000, 350,000, 375,000, or 400,000.

[0119] Tensile testing was performed using aluminum lap shear and Instron. The average strength of PCS of different molecular weights was compared with that of PCS prepared from dimethoxyacetophenone monomer, which showed optimal performance at a molecular weight of 80,000. Despite the different processing methods, the average strength of the different 80,000 molecular weight PCS did not show significant differences. In addition, the PCS produced by this method observed a peak strength at a molecular weight of 122,000. This is surprising because the literature shows that PCS strength increases to the 80,000-100,000 range and then begins to decline.

[0120] In some embodiments, the poly(catechol-styrene) polymer has a polydispersity index (PDI) of about 1 to about 4, such as, for example, about 1, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, about 2, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, or about 4, as measured by GPC.

[0121] In other embodiments, the poly(catechol-styrene) polymer has a polydispersity index (PDI) of about 2 to about 4, such as, for example, about 2, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, about 3, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.9, or about 4, as measured by GPC.

[0122] In other embodiments, the poly(catechol-styrene) polymer has a polydispersity index (PDI) of about 2 to about 4, such as, for example, about 2, about 2.1, about 2.2, about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about 2.9, or about 3, as measured by GPC.

[0123] The emulsion polymerization methods described herein are advantageous because they result in extremely high monomer conversions, typically 99%+. Due to this high monomer conversion, the amount of unreacted monomer to be removed from the product is minimized. Removal of unreacted monomer can be difficult due to the heat and air sensitivity of the product polymer.

[0124] As discussed above, the PCS production method of the present disclosure includes a polymerization reaction and a deprotection reaction. In some embodiments, the polymerization reaction and the deprotection reaction are carried out in separate reaction vessels. In other embodiments, the polymerization reaction and the deprotection reaction are carried out in the same reaction vessel, i.e., in a "one-pot" process.

[0125] Different applications for PCS polymers may require different catechol contents. By adjusting the reaction conditions of the methods described herein, the catechol content of the resulting PCS polymer can be controlled. For example, the catechol content can be controlled by adjusting the weight ratio of styrene monomer to DAS monomer used in the emulsion polymerization reaction, by adjusting the amount of surfactant used in the emulsion polymerization reaction, by adjusting the amount of initiator used in the emulsion polymerization reaction, or by adjusting the amount of chain transfer agent used in the emulsion polymerization reaction. In some embodiments, the catechol content of the PCS polymer produced by the disclosed methods is from about 10 wt % to about 75 wt %, such as, for example, about 10 wt %, about 11 wt %, about 12 wt %, about 13 wt %, about 14 wt %, about 15 wt %, about 16 wt %, about 17 wt %, about 18 wt %, about 19 wt %, about 20 wt %, about 21 wt %, about 22 wt %, about 23 wt %, about 24 wt %, about 25 wt %, about 26 wt %, about 27 wt %, about 28 wt %, about 29 wt %, about 30 wt %, about 31 wt %, about 32 wt %, about 33 wt %, about 34 wt %, about 35 wt %, about 36 wt %, about 37 wt %, about 38 wt %, about 39 wt %, about 40 wt %, about 41 wt %, about 42 wt %, about 43 wt %, about 44 wt %, about 45 wt %, about 46 wt %, about 47 wt %, about 48 wt %, about 49 wt %, about 50 wt %, about 51 wt %, about 52 wt %, about 53 wt %, about 54 wt %, about 55 wt %, about 56 wt %, about 57 wt %, about 58 wt %, about 59 wt %, about 60 wt %, about 61 wt %, about 62 wt %, about 63 wt %, about 64 wt %, about 65 9 wt %, about 40 wt %, about 41 wt %, about 42 wt %, about 43 wt %, about 44 wt %, about 45 wt %, about 46 wt %, about 47 wt %, about 48 wt %, about 49 wt %, about 50 wt %, about 51 wt %, about 52 wt %, about 53 wt %, about 54 wt %, about 55 wt %, about 56 wt %, about 57 wt %, about 58 wt %, about 59 wt %, about 60 wt %, about 61 wt %, about 62 wt %, about 63 wt %, about 64 wt %, about 65 wt %, about 66 wt %, about 67 wt %, about 68 wt %, about 69 wt %, about 70 wt %, about 71 wt %, about 72 wt %, about 73 wt %, about 74 wt %, or about 75 wt %.

[0126] In some embodiments, the PCS polymer produced by the disclosed methods has a catechol content of about 75 wt%.

[0127] In some aspects, the present disclosure relates to a polymerization reaction final product comprising a poly(3,4-diacetoxystyrene-co-styrene) polymer, wherein the unconverted monomer present in the reaction final product is less than 5% of the monomer added to the reaction mixture, such as, for example, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or less than 0.1%. In some embodiments, the unconverted monomer present in the reaction mixture is less than 1% of the monomer added to the reaction mixture.

[0128] In some aspects, the present disclosure relates to a polymerization reaction final product comprising a PCS polymer, wherein the unconverted monomer present in the reaction final product is less than 5% of the monomer added to the reaction mixture, such as, for example, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or less than 0.1%. In some embodiments, the unconverted monomer present in the reaction mixture is less than 1% of the monomer added to the reaction mixture.

[0129] The PCS methods disclosed herein offer several significant advantages over PCS methods using methoxycatechol protecting groups. First, from an economic perspective, PCS methods using methoxycatechol protecting groups require expensive deprotection reagents, making these methods economically unaffordable. In contrast, the methods disclosed herein using acetate protecting groups require much cheaper deprotection reagents. Second, methods using methoxycatechol protecting groups require much higher temperatures (165°C) to complete deprotection. Consequently, the deprotection reaction requires high-boiling-point solvents, such as DMF. These high-boiling-point solvents can be difficult to completely remove during the drying step, potentially compromising the suitability of the resulting PCS for specific uses or applications. For example, the FDA restricts the amount of certain residual solvents for safety reasons, which can hinder the use of PCS prepared with methoxycatechol protecting groups in biomedical applications. The use of certain high-boiling-point solvents also precludes the application of spray drying for large-scale PCS production. The methods disclosed herein avoid all of these issues.

[0130] In this disclosure, the singular forms "a," "an," and "the" include plural references, and a reference to a particular value includes at least that particular value unless the context clearly dictates otherwise. Thus, for example, a reference to "a material" is a reference to at least one of such material and equivalents thereof known to those skilled in the art, and so forth.

[0131] The modifier "about" should be considered to disclose a range defined by the absolute values ​​of the two endpoints. For example, the expression "about 2 to about 4" also discloses a range of "2 to 4." When used to modify a single number, the term "about" can refer to plus or minus 10% of the indicated number, including the indicated number. For example, "about 10%" can indicate a range of 9% to 11%, and "about 1" means 0.9 to 1.1.

[0132] When a list is presented, it should be understood that each individual element of the list and each combination of the lists should be interpreted as a separate embodiment unless otherwise stated. For example, a list of embodiments shown as "A, B, or C" should be interpreted to include embodiments "A," "B," "C," "A or B," "A or C," "B or C," or "A, B, or C."

[0133] In the case of existence, all scopes include end values ​​and can be combined. That is, the reference to the value described in the scope includes each value in the scope. For example, the scope defined as 400ppm to 450ppm includes 400ppm and 450ppm as an independent embodiment. The scope of 400ppm to 450ppm and 450ppm to 500ppm can be combined into the scope of 400ppm to 500ppm. In addition, for the description of this type of scope herein, when listing two or more specific values ​​of a parameter, the disclosure also includes the value of the range limited by any two specific values ​​of two or more specific values ​​of the parameter, including the endpoints of such a scope.

[0134] It should be understood that, for the sake of clarity, certain features of the invention described herein in the context of separate embodiments may also be provided in combination with a single embodiment. That is, unless clearly incompatible or excluded, each separate embodiment is considered to be combinable with any other embodiment, and such combination is considered to be another embodiment. Conversely, for the sake of brevity, the various features of the invention described in the context of a single embodiment may also be provided separately or in any sub-combination. It should also be noted that the claims may be drafted to exclude any optional elements. Thus, this statement is intended to serve as a prerequisite for the use of exclusive terms such as "only", "only" and the like in conjunction with the recitation of claim elements or the use of "negative" limitations. Finally, although an embodiment may be described as part of a series of steps or part of a more general structure, each of said steps may also be considered to be an independent embodiment in itself.

[0135] While the present disclosure has been illustrated by describing several embodiments, and while the exemplary embodiments have been described in considerable detail, the applicants do not intend to restrict or in any way limit the scope of the appended claims to such detail. Additional advantages and modifications may be apparent to those skilled in the art. Furthermore, features from separate lists may be combined; and features from the examples may be summarized in the entire disclosure.

[0136] This disclosure also relates to the following aspects:

[0137] Aspect 1. A method for forming a poly(catechol-styrene) polymer, the method comprising the steps of:

[0138] (i) polymerizing 3,4-diacetoxystyrene and styrene in an emulsion polymerization to form a poly(3,4-diacetoxystyrene-co-styrene) polymer, and

[0139] (ii) deprotecting the acetate groups of the resulting poly(3,4-diacetoxystyrene-co-styrene) polymer to form a poly(catechol-styrene) polymer.

[0140] Aspect 2. The method according to aspect 1, wherein after the poly(3,4-diacetoxystyrene-co-styrene) polymer is formed, it is precipitated.

[0141] Aspect 3. The method according to aspect 2, wherein the precipitated poly(3,4-diacetoxystyrene-co-styrene) polymer is deprotected by dissolving it in a solution and treating it with an acid.

[0142] Aspect 4. The method according to aspect 1, wherein the polymerization step further comprises a surfactant, an initiator, and a chain transfer agent.

[0143] Aspect 5. The method according to aspect 4, wherein the initiator comprises potassium persulfate.

[0144] Aspect 6. The method according to aspect 4, wherein the chain transfer agent comprises dodecyl mercaptan.

[0145] Aspect 7. The method according to aspect 1, wherein the polymerization step and the deprotection step are performed in one pot.

[0146] Aspect 8. The method of aspect 1, wherein after the poly(catechol-styrene) polymer is formed, it is precipitated.

[0147] Aspect 9. The method of aspect 8, wherein the precipitated poly(catechol-styrene) polymer is dissolved in a polar solvent and then precipitated from a non-polar solvent.

[0148] Aspect 10. The method of aspect 1, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is deprotected by treating it with an acid.

[0149] Aspect 11. The method of aspect 10, wherein after the treatment with the acid, the mixture is neutralized with a base, concentrated to a solid, and the poly(catechol-styrene) polymer is dissolved in a polar solvent.

[0150] 12. The method of aspect 11, wherein the dissolved poly(catechol-styrene) polymer is spray dried.

[0151] Aspect 13. A poly(catechol-styrene) polymer formed by the method according to aspect 1.

[0152] Aspect 14. The poly(catechol-styrene) polymer of aspect 13, wherein the poly(catechol-styrene) polymer has a molecular weight of 15k to 188k as measured by GPC.

[0153] Aspect 15. The poly(catechol-styrene) polymer of aspect 13, wherein the poly(catechol-styrene) polymer has a polydispersity index (PDI) of 2 to 3 as measured by GPC.

[0154] Example

[0155] Example 1 - Production of diacetoxy-protected poly(catechol-styrene)

[0156] Styrene (300 ml) and diacetoxystyrene (200 g) were blended with n-dodecyl mercaptan (5 ml) in an Erlenmeyer flask equipped with a magnetic stir bar. The monomer blend was stirred while bubbling argon. An aqueous solution (1500 ml) of sodium lauryl sulfate (3.82 g), cetyl alcohol (9.65 g), potassium persulfate (10.63 g), and sodium bicarbonate (0.001 g) was prepared in a 3-necked round-bottom flask equipped with an overhead stirrer. The emulsion was stirred and heated at 65°C for one hour using a heating mantle. Argon was then bubbled through for one hour. The emulsion was stirred at 200 rpm, and the monomer blend was added. Agitation was increased to 530 rpm, and the temperature was raised to 70°C. Polymerization was allowed to proceed overnight. The next day, the reaction was cooled to room temperature and poured into a stirred saturated saline solution (15,000 ml) to precipitate the polymer. The brine solution was stirred for one hour, then stirring was stopped and the polymer was allowed to settle for one hour.The polymer was recovered by vacuum filtration and deprotected without complete drying.

[0157] Example 2 - Production of Poly(catechol-styrene)

[0158] Diacetoxy-protected poly(catechol-styrene) (233 g) was added to a round-bottom flask equipped with a magnetic stir bar and a reflux condenser. 1200 ml of tetrahydrofuran was added, and the solution was stirred at 45°C using a heating mantle until the polymer was completely dissolved. Six-molar hydrochloric acid (100 ml) was added. The temperature was raised to 70°C, and the reaction was heated for at least 16 hours. Afterwards, the reaction was cooled to room temperature and precipitated into stirred water (15,000 ml). The polymer was stirred for one hour, then stirring was stopped and the polymer was allowed to settle for an additional hour. The water was then decanted, and the polymer was dissolved in acetone (1,000 ml). The acetone-polymer solution was precipitated dropwise into stirred hexane (15,000 ml). The polymer was stirred for one hour, then stirring was stopped and the polymer was allowed to settle for an additional hour. The hexane was decanted, and the polymer was collected and dried in a vacuum oven. Yield: 145 g (71%).

[0159] Example 3 - Polymer Molecular Weight

[0160] The amounts of initiator and chain transfer agent (CTA) were varied to determine their effect on polymer molecular weight. The results are shown in Figure 1 and Figure 2 middle.

[0161] Example 4 (Comparative) - Polymerization

[0162] Polymerization reactions were performed using different amounts of reagents.

[0163]

[0164] Table 1 Reagent Volume

[0165]

[0166] The surfactant was 10 mM SDS.

[0167] Example 5 (Comparative) - Deprotection Reaction

[0168] Deprotection reactions were performed using different amounts of reagents.

[0169]

[0170] Table 2 Reagent Volume

[0171]

[0172] *Lotion

[0173] Example 6 - Dry Adhesion Strength

[0174] The dry adhesion strength of poly(catechol-styrene) polymers prepared by methods using diacetoxy and methoxy protecting groups and their molecular weights were compared. The results are shown in Figure 3 middle.

[0175] Example 7 - Wet Adhesion Strength

[0176] The wet adhesion strength of poly(catechol-styrene) polymers prepared by methods using diacetoxy and methoxy protecting groups were compared along with their molecular weight. The results are shown in Figure 4 middle.

[0177] Example 8 - Poly(catechol-styrene) Polymer Production Method

[0178] Pilot-scale (PCS) production was carried out in three main steps: 1. monomer synthesis, 2. emulsion polymerization, and 3. deprotection of the protected polymer to produce PCS.

[0179] Monomer synthesis. In this first step, a 500 L reaction vessel is charged with dimethylformamide dispensed from an IBC tank. Caffeic acid powder is added and heated until completely dissolved. Triethylamine is pumped from the tank into the reactor and heated to 110°C for two hours. The reactor is then cooled to 25°C, and acetic anhydride is pumped into the reactor. After stirring for 10 hours, the reaction solution is pumped into a storage container. The monomer is separated using a liquid-liquid extraction unit. The reaction fluid is diluted with water and extracted with diethyl ether. The diethyl ether solution of the monomer is then treated with 1 M HCl, followed by a NaCO3 (aqueous) wash and a NaCl wash. The diethyl ether is removed from the purified monomer in an evaporation unit. The diethyl ether is then recycled for subsequent batches.

[0180] Emulsion Polymerization. This second step copolymerizes the diacetoxy monomer (DAS) produced in Step 1 with commercially available styrene in an emulsion process. Sodium lauryl sulfate, cetyl alcohol, potassium persulfate, and sodium bicarbonate are dissolved in water in a 500-L reactor under nitrogen sparging. Styrene, DAS, and n-dodecyl mercaptan are blended in a 200-L tank under nitrogen sparging. The monomer blend is added to the 500-L tank and heated to 70°C with constant stirring for 6 hours. After cooling, the emulsion is transferred to a centrifuge where the water is removed to yield the protected polymer powder, poly(3,4-diacetoxystyrene-co-styrene).

[0181] Deprotection. This final step deprotects the protected polymer to produce PCS. Tetrahydrofuran and poly (3,4-diacetoxystyrene-co-styrene) polymer are loaded into a 1000L reactor. The reactor is heated to 70 ° C and 6M HCl is added. After 24 hours, the reaction mixture is cooled and precipitated into a 5000L tank containing water. The water / THF mixture is discharged from the tank, leaving the solid precipitated PCS, and sent to a recovery tower, thereby allowing both THF and process water to be recycled for subsequent batches. Acetone is thoroughly sprayed into the entire tank to collect all PCS. After the polymer is completely dissolved in acetone, the solution is filtered and pumped to a storage tank. The solution is then sent to a continuous spray dryer to remove the solvent to obtain dry powdered PCS.

[0182] Example 9-PCS synthesis results

[0183] Polymerization reaction

[0184]

[0185]

[0186]

[0187] Deprotection reaction

[0188]

[0189]

Claims

1. A method for forming a poly(catechol-styrene) polymer, the method comprising the steps of: (i) polymerizing 3,4-diacetoxystyrene (DAS) monomer and styrene monomer in an emulsion polymerization reaction to form a poly(3,4-diacetoxystyrene-co-styrene) polymer, and (ii) deprotecting the acetate groups of the resulting poly(3,4-diacetoxystyrene-co-styrene) polymer to form a poly(catechol-styrene) polymer.

2. The method of claim 1, wherein the weight ratio of styrene monomer to DAS monomer used in the emulsion polymerization reaction of step (i) is between about 0.1 and about 5.

0.

3. The method of claim 1, wherein the weight ratio of styrene monomer to DAS monomer used in the emulsion polymerization reaction of step (i) is between about 1.1 and about 1.

9.

4. The method according to claim 1, wherein the emulsion polymerization reaction of step (i) comprises styrene monomer, DAS monomer, surfactant, initiator and chain transfer agent.

5. The method of claim 4, wherein the surfactant is sodium lauryl sulfate.

6. The method of claim 4, wherein the surfactant is cetyl alcohol.

7. The method of claim 4, wherein the surfactant is a mixture of sodium lauryl sulfate and cetyl alcohol.

8. The method of any one of claims 4 to 7, wherein the weight ratio of sodium lauryl sulfate (SLS) to total monomers (styrene + DAS) expressed as a percentage is between about 0.2% and about 6.0%, wherein the percentage is calculated as (weight of SLS) / (weight of DAS + weight of styrene)*100.

9. The method of claim 8, wherein the weight ratio of sodium lauryl sulfate (SLS) to total monomers (styrene + DAS) expressed as a percentage is between about 0.8% and about 3.0%.

10. The method of any one of claims 4 to 9, wherein the weight ratio of cetyl alcohol to total monomers (styrene + DAS) expressed as a percentage is between about 0.5% and about 10.0%, wherein the percentage is calculated as (weight of cetyl alcohol) / (weight of DAS + weight of styrene)*100.

11. The method of claim 10, wherein the weight ratio of cetyl alcohol to total monomers (styrene + DAS) expressed as a percentage is between about 2.0% and about 7.0%.

12. The method of any one of claims 7 to 11, wherein the weight ratio of cetyl alcohol to sodium lauryl sulfate is between about 2.0 and about 4.

0.

13. The method of claim 12, wherein the weight ratio of cetyl alcohol to sodium lauryl sulfate is between about 2.30 and about 2.

80.

14. The method according to any one of claims 4 to 13, wherein the initiator is a water-soluble free radical initiator.

15. The method of claim 14, wherein the ratio of initiator to total monomers expressed as a percentage is between about 0.1% and about 3.0%, wherein the percentage is calculated as (weight of initiator) / (weight of DAS+weight of styrene)*100.

16. The method of claim 15, wherein the ratio of initiator to total monomers expressed as a percentage is between about 1.0% and about 3.0%.

17. The method according to any one of claims 4 to 16, wherein the initiator is sodium persulfate, potassium persulfate, ammonium persulfate, benzoyl peroxide or tert-butyl hydroperoxide.

18. The process according to any one of claims 4 to 17, wherein the chain transfer agent is dodecyl mercaptan (also known as dodecanethiol or n-dodecylmercaptan), carbon tetrachloride or a halogenated hydrocarbon.

19. The method of claim 18, wherein the ratio of chain transfer agent to total monomers expressed as a percentage is between about 0.05% and about 10%, wherein the percentage is calculated as (weight of chain transfer agent) / (weight of DAS+weight of styrene)*100.

20. A process according to claim 18 or claim 19 wherein the chain transfer agent is dodecyl mercaptan.

21. A process according to any one of the preceding claims, wherein the emulsion polymerisation reaction (i) further comprises a buffer, such as sodium bicarbonate.

22. The method according to any one of the preceding claims, wherein the emulsion polymerization (i) further comprises an aqueous solvent, such as water.

23. The method of any one of the preceding claims, wherein the amount of water used in the emulsion polymerization reaction is from about 190 grams to about 320 grams of total monomer per liter of water, based on the total monomer used.

24. The method of any one of the preceding claims, wherein the emulsion polymerization reaction is carried out at an elevated temperature of about 40°C to about 100°C.

25. The method of claim 24, wherein the emulsion polymerization is carried out at a temperature of about 70°C.

26. The process according to any one of the preceding claims, wherein the emulsion polymerization is carried out in an argon or nitrogen atmosphere.

27. The method of any one of the preceding claims, wherein the emulsion polymerization reaction is stirred at an elevated temperature for a period of about 3 hours to 8 hours.

28. The method of any preceding claim, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is isolated from a polymerization reaction mixture.

29. The method of claim 28, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is isolated from the polymerization reaction mixture by precipitation and filtration.

30. The method of claim 29, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is precipitated by cooling the polymerization reaction mixture.

31. The method of claim 29, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is precipitated by mixing the polymerization reaction mixture with a salt solution.

32. The method of any one of claims 29 to 31, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is precipitated by cooling the polymerization reaction mixture and mixing with a salt solution.

33. A process according to any one of claims 29 to 32, wherein the precipitated polymer is filtered and washed with a solvent such as water.

34. The process of any one of the preceding claims, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is precipitated by cooling the polymerization reaction mixture and then separated by transferring the mixture to a centrifuge where water is removed to obtain a protected polymer powder.

35. The method of any preceding claim, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer produced by emulsion polymerization has a molecular weight in the range of about 25,000 to about 1,100,000.

36. The method of claim 35, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer produced by the emulsion polymerization has a molecular weight in the range of about 25,000 to about 300,000.

37. The method of any preceding claim, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer produced by the emulsion polymerization has a polydispersity index (PDI) of about 2 to about 30.

38. The method of claim 37, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer produced by the emulsion polymerization has a polydispersity index (PDI) of about 2 to about 4.

39. The method of any preceding claim, wherein the emulsion polymerization reaction results in conversion of at least 95% of the total monomers (DAS + styrene) to polymer.

40. The method of any preceding claim, wherein the deprotection reaction step (ii) is performed by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with an aqueous acid solution.

41. The method of claim 40, wherein the aqueous acid solution is selected from hydrochloric acid (HCl), p-toluenesulfonic acid (p-TsOH), fluoroboric acid (HBF4), camphorsulfonic acid (CSA), nitric acid, and combinations thereof.

42. The method of claim 40 or claim 41, wherein the deprotection reaction is performed by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with an acid in an amount of 0.9 to 1.9 mmol of acid per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer.

43. The method of claim 42, wherein the deprotection reaction is performed by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with an acid in an amount of 1.4 to 1.5 mmol of acid per gram of poly(3,4-diacetoxystyrene-co-styrene) polymer.

44. The method of any one of claims 40 to 43, wherein the acid is added to the deprotection reaction in the form of a 1M to 8M solution.

45. The method of any one of claims 40 to 44, wherein the acid is HCl.

46. ​​The method of claim 45, wherein the deprotection reaction is performed by treating the poly(3,4-diacetoxystyrene-co-styrene) polymer with 6M HCl.

47. The method of any preceding claim, wherein the deprotection reaction comprises dissolving the poly(3,4-diacetoxystyrene-co-styrene) polymer in a solvent.

48. The method of claim 47, wherein the solvent is acetone, THF, or dimethylformamide (DMF).

49. The method of claim 47 or claim 48, wherein the poly(3,4-diacetoxystyrene-co-styrene) polymer is dissolved in the solvent at a concentration of 280 to 500 grams of poly(3,4-diacetoxystyrene-co-styrene) polymer per liter of solvent.

50. The method of any one of claims 40 to 49, wherein the deprotection reaction is performed by heating the reaction mixture to an elevated temperature, such as from about 40°C to about 100°C.

51. The method of claim 50, wherein the deprotection reaction is performed by heating the reaction mixture to about 70°C.

52. The method of any one of the preceding claims, wherein the deprotection reaction is allowed to proceed for up to 48 hours.

53. The process according to any one of claims 40 to 52, wherein after deprotection, the deprotection reaction mixture is neutralized by adding a base such as sodium bicarbonate.

54. The method of any preceding claim, wherein the poly(catechol-styrene) polymer is isolated by precipitation and filtration.

55. The method of claim 54, wherein the poly(catechol-styrene) polymer is precipitated by cooling the deprotection reaction mixture to about 25°C to 35°C and then adding a solvent such as water to the reaction mixture.

56. A method according to claim 54 or claim 55, wherein the precipitated poly(catechol-styrene) polymer is collected by filtration.

57. The method of any one of claims 54 to 56, wherein the poly(catechol-styrene) polymer precipitate is redissolved in a polar solvent such as acetone, dichloromethane, methyl ethyl ketone, and DMF.

58. The method of claim 57, wherein the solvent is acetone.

59. A method according to claim 57 or claim 58, wherein the dissolved poly(catechol-styrene) polymer is precipitated by adding a non-polar solvent such as hexane or diethyl ether.

60. The method of claim 57 or claim 58, wherein the dissolved poly(catechol-styrene) polymer is precipitated by removing the solvent by evaporation.

61. The method of claim 57 or claim 58, wherein the dissolved poly(catechol-styrene) polymer is precipitated by spray drying to provide a solid poly(catechol-styrene) polymer.

62. The method of any preceding claim, wherein the poly(catechol-styrene) polymer produced by the method has a molecular weight in the range of 15,000 to 1,000,000 as measured by GPC.

63. The method of claim 62, wherein the poly(catechol-styrene) polymer produced by the method has a molecular weight in the range of about 50,000 to about 400,000 as measured by GPC.

64. The method of any preceding claim, wherein the poly(catechol-styrene) polymer produced by the method has a polydispersity index (PDI) of about 1 to about 4 as measured by GPC.

65. A polymerization reaction end product comprising a poly(3,4-diacetoxystyrene-co-styrene) polymer, wherein unconverted monomers present in the reaction end product are less than 5% of the monomers added to the reaction mixture.

66. The polymeric end product of claim 65, wherein the unconverted monomer present in the reaction mixture is less than 1% of the monomer added to the reaction mixture.

67. The polymeric final product of claim 65, wherein the unconverted monomer present in the reaction mixture is less than 0.5% of the monomer added to the reaction mixture.

68. A polymerization end product comprising a PCS polymer wherein the unconverted monomers present in the reaction mixture are less than 5% of the monomers added to the reaction mixture.

69. The polymeric end product of claim 68, wherein the unconverted monomer present in the reaction mixture is less than 1% of the monomer added to the reaction mixture.

70. The polymeric end product of claim 68, wherein the unconverted monomer present in the reaction mixture is less than 0.5% of the monomer added to the reaction mixture.

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