Electrochemical detection of chemical warfare agents

Abstract

tert-butyl 1’-methoxycarbonyl-1-ferrocenecarbamate, Boc-NH-Fc-COOMe, (1) was synthesized according to the literature procedure and modified to 1-amino-n′-ferrocenemethylcarboxylate, 1,n′-H2N-Fc-COOCH3 (2) by removing the Boc-group with TFA/Et3N mixture in dichloromethane. Compound 2 reacted with alkylating agents like MeI, EtI, EtSCH2CH2Cl (MA) and (CN)(EtO)2P(O) (NA) to form MeNH-Fc-COOMe (3), EtNH-Fc-COOMe (4), EtSCH2CH2NH-Fc-COOMe (5), (EtO)2P(O)NH-Fc-COOMe (6), respectively. Cyclic voltammetry (CV) of these compounds showed different half-wave potential characteristics compared to aminoferrocene and was dependent on the nature of the substituents, which was rationalized by molecular orbital calculations. Electron donating groups (Me, Et and 2-chloroethyl ethylsulfide, MA) shifted the half-wave potential towards the cathodic direction while electron withdrawing group like diethyl cyanophosphonate, NA, shifted it toward anodic direction. Anodic to cathodic peak separation were found to be within 62-88 mV indicating a quasi-reversible system. Hydrolysis of compound 1 resulted in the formation of tert-butyl 1’-methoxycarbonyl-1-ferrocenecarboxylic acid, Boc-NH-Fc-COOH, (11) which was coupled with cystamine using the EDC/HOBt protocol to synthesize the cystamine conjugate [BocHN-Fc-CO-CSA]2 (12). This molecule is equipped with an amino group that directly linked to the redox receptor. Compound 12 was fully characterized by spectroscopic methods and by single crystal x-ray diffraction. The cystamine conjugate 12 formed films on gold substrates, which upon deprotection of the amino group, reacted with chemical warfare agents (CWAs) mimics, such as EtSCH2CH2Cl (MA), a simulant for the sulfur mustard HD, and (CN)(EtO)2P(O) (NA), a simulant for the nerve agent Tabun. Their reaction with the surface-bound ferrocene derivative results in the formation of N-substituted products. CV measurements showed anodic shifts of the Fc redox potentials by 50 (±5) mV after exposure to MA, and NA. Measurements by quartz crystal microbalance (QCM) showed an increase in mass upon exposure to MA and NA. Ellipsometry measured a film thickness increase from 6 (±1) Å for the deprotected film to 10 (±4) Å for the film modified with MA and to 7 (±2) Å for the film modified with NA. The surfaces were analyzed by x-ray photoelectron spectroscopy (XPS) and clearly showed the attachment of the cystamine conjugate on the surface and its reaction with CWAs mimics.