Methods and materials for detection of arsenic

Abstract

This invention relates to methods and materials for detection of metal ions, such as by utilization of coordination complexes with metal ions of interest, such as particular arsenic ions. In particular, this invention relates to methods and materials for detection of a particular arsenic ion (As(III)), utilizing coordination complexes with the arsenic ion and performing a detection operation, such as measuring absorbance of the coordination complexes at particular wavelengths, or other appropriate detection operations.

Description

Attorney Docket No. / Customer No. P-ARSN-1000PC 1 / 72,007 Filed Electronically via EFS-WEB Filing Date: December 10, 2025METHODS AND MATERIALS FOR DETECTION OF ARSENICCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a Patent Cooperation Treaty (PCT) international application that claims the benefit and priority of U.S. provisional patent application Ser. No. 63 / 730,423, filed December 10, 2024, and the contents of that application are hereby incorporated by reference in its entirety.COPYRIGHT NOTICE

[0002] A portion of the disclosure of this patent document contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the U.S. Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever.FIELD OF THE INVENTION

[0003] This invention relates to methods and materials for detection of specific ionic species of metals, particularly to detection of arsenic(III).BACKGROUND OF THE INVENTION

[0004] Arsenic is an environmental toxin with severe consequences on human health. While the prevalence of arsenic in drinking water is more problematic in certain regions of the world than others, its toxicity is such that it is routinely monitored in water treatment facilities worldwide. Although arsenic exists in many different chemical forms in nature, it is found almost exclusively as arsenite (As(III) as H3ASO3) and arsenate (As(V) as H3ASO4) in water. As(III) was identified as one of the most harmful substances in water to human health, and is 60 times more toxic than As(V) or organic arsenic compounds. In 2001, the U.S. EPA and the World Health Organization lowered the maximum contaminant level (MCL) guideline for arsenic in drinking water from 50 to 10 ppb.SUMMARY OF THE INVENTIONAttorney Docket No. / Customer No. P-ARSN-1000PC1 / 72007

[0005] This invention relates to methods and materials for detection of specific ionic species of metals, particularly to detection of arsenic(III). In some exemplary embodiments, detection may utilize complexing agents bound to specific valence states of a metal such that the detection may discriminate between valence states of a metal. For example, it may be desirable to select for functional ligands to As(III) as opposed to other valence states, such as As(V), as As(III) is much more toxic to humans and both species may bind to arsenic-binding complexing agents.

[0006] The present invention together with the above and other advantages may best be understood from the following detailed description of the embodiments of the invention and as illustrated in the drawings. The following description, while indicating various embodiments of the invention and numerous specific details thereof, is given by way of illustration and not of limitation. Many substitutions, modifications, additions or rearrangements may be made within the scope of the invention, and the invention includes all such substitutions, modifications, additions or rearrangements.BRIEF DESCRIPTION OF THE FIGURES

[0007] FIG. 1 illustrates an example of the absorption spectrum of arsenic(III) ions with a complexing agent;

[0008] FIG. 2 illustrates an example of a concentration-dependent absorption response at 310 nm for arsenic(III) (As(III)) ions with a complexing agent; and

[0009] FIG. 3 illustrates examples of absorption spectra of other metal ions with a complexing agent.DETAILED DESCRIPTION OF THE INVENTION

[0010] The detailed description set forth below is intended as a description of the presently exemplified methods, devices, and compositions provided in accordance with aspects of the present invention and is not intended to represent the only forms in which the present invention may be practiced or utilized. It is to be understood, however, that the same or equivalent functions and components may be accomplished by different embodiments that are also intended to be encompassed within the spirit and scope of the invention.

[0011] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this inventionAttorney Docket No. / Customer No. P-ARSN-1000PC1 / 72007 belongs. Although any methods, devices and materials similar or equivalent to those described herein can be used in the practice or testing of the invention, the exemplified methods, devices and materials are now described.

[0012] This invention relates to methods and materials for detection of specific ionic species of metals, particularly to detection of arsenic(III) (As(III)). In some exemplary embodiments, detection may utilize complexing agents bound to specific valence states of a metal such that the detection may discriminate between valence states of a metal. For example, it may be desirable to select for functional ligands to As(III) as opposed to other valence states, such as As(V), as As(III) is much more toxic to humans and both species may bind to arsenic-binding complexing agents.

[0013] In some embodiments, chelating and / or other complexing agents may be utilized which exhibit specific conformations or other distinguishable structural features when bound to the desired ionic species as opposed to unbound states or states where bound to an undesired ionic species. In general and without being bound to any particular theory, chelating agents may be utilized that create trigonal-pyramidal coordination geometries with As(III) with a stereochemically active lone pair when coordinated by ligands with properly oriented lone pairs and / or stabilized by interactions with phenyl rings or similar molecular features. Examples and characteristics of such molecules and their interactions with As(III) are described by Vickaryous et al. (Vickaryous, W. I., Herges, R., Johnson, D. W.; “Arsenic — Interactions Stabilize a Self- Assembled As2L3 Supramolecular Complex”; Angew. Chem. Int. Ed. 2004, 43, 5831), which is hereby incorporated by reference in its entirety. Examples of coordination, chelating and / or complexing agents, such as for specifically or distinguishably binding As(III), may include, but are not limited to, thiol-containing molecules, such as organothiolate ligands as illustrated in FIG. 2, bis(mercaptomethyl)benzene (FIG. 2a), 2-(pyridin-2-yl)-2,3-dihydrobenzo[d]thiazole (FIG. 2b). Other examples include, but are not limited to, 4-(mercaptomethyl)benzoic acid, 1,4- benzenedimethanethiol (i.e. a,a’-dimercapto-para-xylene, BDMT), meso-2,3-dimercaptosuccinic acid, 2, 3 -dimercapto- 1 -propanesulfonic acid, 2,3-dimercapto-l-propanol, and / or any other appropriate chelating agent. It may further be desirable that the ionic state of the ionic species be maintained during a detection. In general, and without being bound to any particular theory, antioxidants may be utilized to aid in maintaining the oxidation state of the ionic species (e.g. maintaining As(III) and preventing oxidation to As(V)), such as by using ascorbic acid and / or any other appropriate antioxidant.Attorney Docket No. / Customer No. P-ARSN-1000PC1 / 72007

[0014] In some embodiments, after complexing with the ionic species, detection may generally be accomplished by measurement of absorbance on an ultraviolet-visible (UV-Vis) spectrophotometer, a single-wavelength detector and / or other similar or appropriate devices for measuring absorbance.

[0015] In other embodiments, other detection methods and / or mechanisms may be utilized, such as through surface detection techniques. For example, a coordination, chelating and / or complexing agent may be attached, immobilized and / or otherwise coupled to a surface, such as through a chemical modification to the ligand, and detection may be done by, for example, electrochemical sensing.

[0016] In still other embodiments, a coordination, chelating and / or complexing agent may be chemically modified to include a reactive group (e.g. methylene blue), an electrochemical reporter moiety, fluorescence moiety for fluorescence detection (e g. quenchers, dyes, etc ), and or other modification for detection.

[0017] In further embodiments, combinations of the detection methods discussed herein may be utilized.EXAMPLE OF SPECIFIC DETECTION OF ARSENIC(III)

[0018] An example of detection of As(III) ions in aqueous solution was performed with arsenic(III) chloride (Sigma Aldrich Catalog No. 200077-25g) at varying concentrations of 0, 0.125, 0.25, 0.5, 1 and 2 pM in a buffer solution of 10 mM Tricine, 1 mg / mL ascorbic acid at pH 4.5. A complexing / coordination agent was utilized in the form of 3 pM 1,4-benzenedimethanethiol (BDMT). The BDMT and As(III) solutions was allowed to incubate at room temperature with rotation. The solutions were examined in a Nanodrop UV-Vis Spectrophotometer between wavelengths of 275 nm and 320 nm, yielding the absorption spectrum shown in FIG. 1 showing a detectable increase in absorption versus the 0 pM baseline between approximately 290 nm and 320 nm. A concentration-dependent response at 310 nm illustrated in FIG. 2. For comparison, absorption spectra are illustrated in FIG. 3 for 3 pM BDMT and other metal ion species, including iron (Fe), copper (Cu) and zinc (Zn), showing specific interaction between BDMT and As(III) and negligible interaction with the other metals.

[0019] Although the invention has been described with respect to specific embodiments thereof, these embodiments are merely illustrative, and not restrictive of the invention. TheAttorney Docket No. / Customer No. P-ARSN-1000PC1 / 72007 description herein of illustrated embodiments of the invention, including the description in the Abstract and Summary, is not intended to be exhaustive or to limit the invention to the precise forms disclosed herein (and in particular, the inclusion of any particular embodiment, feature or function within the Abstract or Summary is not intended to limit the scope of the invention to such embodiment, feature or function). Rather, the description is intended to describe illustrative embodiments, features and functions in order to provide a person of ordinary skill in the art context to understand the invention without limiting the invention to any particularly described embodiment, feature or function, including any such embodiment feature or function described in the Abstract or Summary. While specific embodiments of, and examples for, the invention are described herein for illustrative purposes only, various equivalent modifications are possible within the spirit and scope of the invention, as those skilled in the relevant art will recognize and appreciate. As indicated, these modifications may be made to the invention in light of the foregoing description of illustrated embodiments of the invention and are to be included within the spirit and scope of the invention. Thus, while the invention has been described herein with reference to particular embodiments thereof, a latitude of modification, various changes and substitutions are intended in the foregoing disclosures, and it will be appreciated that in some instances some features of embodiments of the invention will be employed without a corresponding use of other features without departing from the scope and spirit of the invention as set forth. Therefore, many modifications may be made to adapt a particular situation or material to the essential scope and spirit of the invention.

[0020] Reference throughout this specification to "one embodiment", "an embodiment", or "a specific embodiment" or similar terminology means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment and may not necessarily be present in all embodiments. Thus, respective appearances of the phrases "in one embodiment", "in an embodiment", or "in a specific embodiment" or similar terminology in various places throughout this specification are not necessarily referring to the same embodiment. Furthermore, the particular features, structures, or characteristics of any particular embodiment may be combined in any suitable manner with one or more other embodiments. It is to be understood that other variations and modifications of the embodiments described and illustrated herein are possible in light of the teachings herein and are to be considered as part of the spirit and scope of the invention.Attorney Docket No. / Customer No. P-ARSN-1000PC1 / 72007

[0021] In the description herein, numerous specific details are provided, such as examples of components and / or methods, to provide a thorough understanding of embodiments of the invention. One skilled in the relevant art will recognize, however, that an embodiment may be able to be practiced without one or more of the specific details, or with other apparatus, systems, assemblies, methods, components, materials, parts, and / or the like. In other instances, well-known structures, components, systems, materials, or operations are not specifically shown or described in detail to avoid obscuring aspects of embodiments of the invention. While the invention may be illustrated by using a particular embodiment, this is not and does not limit the invention to any particular embodiment and a person of ordinary skill in the art will recognize that additional embodiments are readily understandable and are a part of this invention.

[0022] As used herein, the terms “comprises,” “comprising,” "includes," "including," "has," "having," or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, product, article, or apparatus that comprises a list of elements is not necessarily limited only those elements but may include other elements not expressly listed or inherent to such process, process, article, or apparatus.

[0023] Furthermore, the term "or" as used herein is generally intended to mean "and / or" unless otherwise indicated. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present). As used herein, including the claims that follow, a term preceded by "a" or "an" (and "the" when antecedent basis is "a" or "an") includes both singular and plural of such term, unless clearly indicated within the claim otherwise (i.e., that the reference "a" or "an" clearly indicates only the singular or only the plural). Also, as used in the description herein, the meaning of "in" includes "in" and "on" unless the context clearly dictates otherwise.

Claims

Attorney Docket No. / Customer No. P-ARSN-1000PC1 / 72007CLAIMS1. A method for detecting an ionic species comprising: contacting a solution which may contain a target ionic species comprising arsenic(III) ion with a coordination compound, said coordination compound adopting a specific conformation when complexed with said target ionic species; incubating said solution to encourage formation of said specific conformation of said target ionic species and said coordination compound; and measuring an absorbance of said solution in a range within ultraviolet and visible light.

2. The method of claim 1, wherein said coordination compound is selected from the group consisting of of 4-(mercaptomethyl)benzoic acid, 1,4-benzenedimethanethiol, meso-2,3- dimercaptosuccinic acid, 2,3-dimercapto-l-propanesulfonic acid, 2,3-dimercapto-l-propanol, bis(mercaptomethyl)benzene and 2-(pyridin-2-yl)-2,3-dihydrobenzo[d]thiazole.

3. The method of claim 2, wherein said absorbance is measured between 275 nm and 320 nm.

4. The method of claim 2, wherein said absorbance is measured at 310 nm and said coordination compound comprises 1,4-benzenedimethanethiol.

5. A method for detecting an ionic species comprising: contacting a solution which may contain a target ionic species comprising arsenic(III) ion with a coordination compound, said coordination compound adopting a specific conformation when complexed with said target ionic species; incubating said solution to encourage formation of said specific conformation of said target ionic species and said coordination compound; and performing a detection operation.

6. The method of claim 5, wherein said coordination compound is selected from the group consisting of of 4-(mercaptomethyl)benzoic acid, 1,4-benzenedimethanethiol, meso-2,3- dimercaptosuccinic acid, 2,3-dimercapto-l-propanesulfonic acid, 2,3-dimercapto-l-propanol, bis(mercaptomethyl)benzene and 2-(pyridin-2-yl)-2,3-dihydrobenzo[d]thiazole.

7. The method of claim 5, wherein said detection method is selected from the group consisting of absorbance spectrum detection, surface detection, electrochemical sensing, electrochemical reporter reactions, fluorescence detection, and combinations thereof.Attorney Docket No. / Customer No. P-ARSN-1000PC1 / 720078. The method of claim 5, wherein at least a portion of said coordination compound is chemically modified to respond to said detection operation.

9. The method of claim 5, wherein at least a portion of said coordination compound is at least partially immobilized on a surface.

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