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Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C 6 H 8 Backbone Substituents: Synthesis, Characterization, and Antiproliferation Activity

Abstract A series of isomeric bis(alkylthiocarbamate) copper complexes have been synthesized, characterized, and evaluated for antiproliferation activity. The complexes were derived from ligand isomers with 3‐methylpentyl (H 2 L 2 ) and cyclohexyl (H 2 L 3 ) backbone substituents, which each yield a pair of linkage isomers. The thermodynamic products CuL 2a/3a have two imino N and two S donors resulting in three five‐member chelate rings (555 isomers). The kinetic isomers CuL 2b/3b have one imino and one hydrazino N donor and two S donors resulting in four‐, six‐, and five‐member rings (465 isomers). The 555 isomers have more accessible Cu II/I potentials (E 1/2 =−811/−768 mV vs. ferrocenium/ferrocene) and lower energy charge transfer bands than their 465 counterparts (E 1/2 =−923/‐854 mV). Antiproliferation activities were evaluated against the lung adenocarcinoma cell line (A549) and nonmalignant lung fibroblast cell line (IMR‐90) using the MTT assay. CuL 2a was potent ( A549 EC 50 =0.080 μM) and selective ( IMR‐90 EC 50 / A549 EC 50 =25) for A549. Its linkage isomer CuL 2b had equivalent A549 activity, but lower selectivity ( IMR‐90 EC 50 / A549 EC 50 =12.5). The isomers CuL 3a and CuL 3b were less potent with A549 EC 50 values of 1.9 and 0.19 M and less selective with IMR‐90 EC 50 / A549 EC 50 ratios of 2.3 and 2.65, respectively. There was no correlation between reduction potential and A549 antiproliferation activity/selectivity.

Chemistry↗

Synthesis of porous organic cage CC3 via solvent modulated evaporation

We demonstrate a Humidity Modulated Solvent Evaporation (HMSE) approach to promote the nucleation and growth of CC3 crystals. This approach relies on the gradual evaporation of dichloromethane (solvent) from a diluted concentration of CC3 precursors deposited on aluminum foil. The slow solvent evaporation allowed enough time for the organization and formation of CC3 porous organic cage. The solvent diffusion rate was modulated by the relative humidity in the system. The slow kinetics implied during the development of CC3 phase, allowed the formation of CC3 crystals. HRTEM, SAED, SEM, and XRD patterns were used as pivotal characterization techniques to follow and confirm the formation of CC3 crystals.

porous organic cages, modulated evaporation, cryst↗