Author Type

Graduate Student

Date of Award

Summer 6-5-2026

Document Type

Dissertation

Publication Status

Version of Record

Submission Date

July 2026

Department

Chemistry and Biochemistry

College Granting Degree

Charles E. Schmidt College of Science

Department Granting Degree

Chemistry and Biochemistry

Degree Name

Doctor of Philosophy (PhD)

Thesis/Dissertation Advisor [Chair]

Charles Carraher

Abstract

This research aimed to synthesize organometallic polymers from dialkyl (methyl, ethyl, butyl, cyclohexyl, and octyl) and diaryl (phenyl) tin dichlorides and three organic monomers, dipicolinic acid (DPA), chloramphenicol (CH), and isomannide (IS), using interfacial polymerization. Structure-activity relationships were investigated through physicochemical characterization (light-scattering photometry, proton NMR, and IR spectroscopy) and cytotoxicity was evaluated against six human cancer cell lines (AsPC-1, PANC-1, MCF-7, MDA-MB-231, HT-29, PC-3), with cisplatin serving as the reference standard.

Five DPA/tin polymers were synthesized, with IC50 values in the range of 0.60–0.71 μg/mL. Their cytotoxicity was significantly lower than that of cisplatin (0.0023-0.044 μg/mL), suggesting that DPA's strong chelation stabilizes the tin center and impedes the release of the active species at the target site. Five CH/tin polymers were synthesized, achieving IC50 values ranging from 0.20-0.39 μg/mL with cytotoxicity as low as 0.21 μg/mL against PANC-1 (dimethyltin and butyltin), indicating a possibly additive effect of tin and chloramphenicol. Cytotoxicity, however, still fell below that of cisplatin for the chloramphenicol polymers. Five IS/tin polymers were synthesized. Isomannide polymers displayed the widest cytotoxicity range (0.00003 μg/mL to >60 μg/mL). The dimethyltin derivative exhibited an IC50 of 0.00003 μg/mL against PANC-1, surpassing cisplatin's cytotoxicity by nearly two orders of magnitude. The dimethyltin polymers also showed strong cytotoxicity across other tested lines: PC-3 (0.0036 μg/mL), MDA-MB-231 (0.0015 μg/mL), and HT-29 (0.0044 μg/mL). In addition, the dicyclohexyltin polymer inhibited PANC-1 at the nanogram/mL level (0.00013 μg/mL). The results suggest Isomannide's hydrophilicity, combined with small organotin alkyl groups, produces a moderately chelated complex with controlled hydrolysis that maximizes metal release at the target site.

Metallocene polymers (Ti, Zr, Hf) were also synthesized and tested but were generally less cytotoxic than the organotin systems. No single R-group consistently maximized cytotoxicity; instead, cytotoxicity depended on the combined effects of metal, R-group, and organic monomer in optimizing hydrophilic–lipophilic balance. Future work should address solubility limitations through PEG incorporation or nanoparticle formulation, improve structural characterization (TGA, MALDI-MS, elemental analysis), and investigate mechanisms underlying the extraordinary cytotoxicity of dimethyltin/isomannide polymers to inform rational design of future organometallic anticancer agents.

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