Novel ferrocenyl benzoyl peptide esters as anti-cancer agents and ferrocenoyl self assembled monolayers as anion sensors

A series of novel N-(ferrocenyl)benzoyl peptide esters have been synthesized, characterized and screened in vitro against the non-small cell lung cancer cell line, H1299 (cisplatin and carboplatin resistant variant). The potential production of hydroxyl radicals would be enhanced by the benzoyl spacer as this lowers the redox potential of the ferrocene moiety thus making the iron atom easier to oxidize. The peptide chain would also be able to interact with biomolecules via hydrogen bonding. A series of N-(ferrocenyl)2 and N-(ferrocenoyl)2 cystine dimethyl esters have also been synthesized, characterized and immobilized onto gold electrodes. The electroactivity of the ferrocene and the hydrogen bonding ability of the peptide amide bonds will be exploited in the sensing of anions in aqueous media. The synthesis of each series of compounds was achieved by coupling the free N-terminus of various amino acid and peptide esters to the carboxyl group of ferrocenyl benzoic acid (ortho, meta and para) or ferrocenecarboxylic acid using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBt) coupling protocol. All compounds were characterized by a range of spectroscopic techniques including: 1H, 13C, DEPT 135 and HMQC NMR in addition to IR, UV-Vis, MS and CV. The biological effects of orientation around the central benzoyl moiety, increasing peptide chain length and lipophilicity were investigated for the N-(ferrocenyl)benzoyl peptide esters. The most active compound was found to be N-{meta-(ferrocenyl)- benzoyl}-glycine-L-alanine ethyl ester with an IC50 value of 4.0 μM while N-{ortho-(ferrocenyl)-benzoyl}-glycine-L-alanine ethyl ester induced a block in the G2/M phase of the cell cycle. {N-ortho-(ferrocenyl)-benzoyl}2-L-cystine dimethyl ester displayed a linear amperometric response to chloride anions in aqueous media while {N-(ferrocenoyl)-β- alanine}2-L-cystine dimethyl ester exhibited a linear response to nitrate, dihydrogen phosphate and adenosine nucleotides. For adenosine nucleotides {N-(ferrocenoyl)-β- alanine}2-L-cystine dimethyl ester showed a nanomolar sensitivity in aqueous media.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

Dublin City University

Year dc:date.issued

2009

Author dc:creator

• Corry, Alan J.

• Organic chemistry
• Chemistry

Language dc:language

en