Rhenium(I) tricarbonyl complexes of salicylaldehyde semicarbazones: Synthesis, crystal structures and cytotoxicity

A series of N,N-disubstituted salicylaldehyde semicarbazones (SSCs), HOC6H4CHN-NHCONR2, and their rhenium(I) tricarbonyl complexes, [ReBr(CO)3(SSC)], have been synthesised and characterised by IR and 1H NMR spectroscopy. Crystallographic analysis of the complex [ReBr(CO)3(H2Bu2)] (H2Bu2 = SSC where R = Bun) showed that the SSC acts as a bidentate ligand via its imino nitrogen and carbonyl oxygen atoms. The [ReBr(CO)3(SSC)] complexes exhibit moderate to high cytotoxicities towards MOLT-4 cells (IC50 = 1–24 μM, cf. 18 μM for cisplatin), and the majority of them are virtually non-toxic against non-cancerous human fibroblasts. Apoptotic assays of [ReBr(CO)3(H2Bnz2)] (Bnz = benzyl) revealed that it mediates cytotoxicity in MOLT-4 cells via apoptosis. The complex [ReBr(CO)3(H2Bnz2)] reacts with guanosine by proton transfer from the phenolic OH group to N(7) of guanosine. In (CD3)2SO, [ReBr(CO)3(H2Bnz2)] undergoes facile conversion to the dimeric complex, [Re(CO)3(HBnz2)]2, via bromide dissociation.

Graphical abstractA series of N,N-disubstituted salicylaldehyde semicarbazones (SSCs) and their rhenium(I) tricarbonyl complexes have been synthesised and characterised. The complexes exhibit moderate to high cytotoxicities towards MOLT-4 cells. Most of the SSCs and complexes demonstrate negligible activity against non-cancerous human fibroblasts.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The title complexes are active against MOLT-4 leukaemia cells. ► They are mostly non-toxic against non-cancerous human fibroblasts. ► The dibenzyl substituted complex (1) is active against MCF-7 breast cancer cells too. ► The phenolic OH group of 1 protonates N(7) of guanosine. ► In DMSO, 1 undergoes bromide dissociation but not displacement of the semicarbazone.