Richard E. Bozak

Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups

Induction of phase 2 enzymes and elevations of glutathione are major and sufficient strategies for protecting mammals and their cells against the toxic and carcinogenic effects of electrophiles and reactive forms of oxygen. Inducers belong to nine chemical classes and have few common properties except for their ability to modify sulfhydryl groups by oxidation, reduction, or alkylation. Much evidence suggests that the cellular “sensor” molecule that recognizes the inducers and signals the enhanced transcription of phase 2 genes does so by virtue of unique and highly reactive sulfhydryl functions that recognize and covalently react with the inducers. Benzylidene-alkanones and -cycloalkanones are Michael reaction acceptors whose inducer potency is profoundly increased by the presence of ortho- (but not other) hydroxyl substituent(s) on the aromatic ring(s). This enhancement correlates with more rapid reactivity of the ortho-hydroxylated derivatives with model sulfhydryl compounds. Proton NMR spectroscopy provides no evidence for increased electrophilicity of the β-vinyl carbons (the presumed site of nucleophilic attack) on the hydroxylated inducers. Surprisingly, these ortho-hydroxyl groups display a propensity for extensive intermolecular hydrogen bond formation, which may raise the reactivity and facilitate addition of mercaptans, thereby raising inducer potencies.

Redox potential and substituent effects in ferrocene derivatives: II

Abstract The anodic behavior of 31 ferrocene derivatives (FcX) (four of which have been prepared for the first time) of the types shown below has been investigated by cyclic voltammetry (and, in some cases, also by controlled-potential electrolysis and differential pulse polarography) at a Pt electrode, in an aprotic solvent: FcC(Y)Z (class A; Y  R (hydrogen, alkyl or unsaturated-carbon moiety) or Cl; Z  CRR′, derived functionalized groups or {W(CO) 5 }); FcC(Y)O (class B; Y  R or OH); other types (class C, including azide, other unsaturated N moieties, acyloxy or phosphino); disubstituted ferrocenes (class D, with alkyl, aminoalkyl, phosphino, B(OH) 2 or −HGCl substituents, or the SSS bridge). All these substituted ferrocenes exhibit a one-electron reversible oxidation centered at iron and the effect of the substituents on the half-wave oxidation potential is discussed in terms of electronic properties. Using the accepted linear correlations between the half-wave oxidation potential and the Hammett constant σ p of the substituent, σ p was estimated for the first time for 29 of the substituents in the ferrocenes listed above. The anomalous behavior of complexes with a hydroxy or a carbonyl group is discussed. No correlation was observed between the oxidation potential and either the energy of the electronic absorption bands or the 1 H NMR chemical shift of the unsubstituted cyclopentadienyl ring, although there are rough correlations for class A compounds. This behaviour is compared with those of [Fc-CHYZ]. kw]Iron; Redox potentials; Ferrocenes; Electrochemistry; Substituent effects

Comparison of structure, logP and P388 cytotoxicity of some phenyl and ferrocenyl cyclic chalcone analogues. Application of RP-TLC for logP determination of the ferrocenyl analogues

AbstractCyclic chalcone analogues (2–5) and their ferrocenyl counterparts (6–10) were synthesized and their logP and P388 cyctotoxity were investigated. The structures of the newly synthesized compounds were confirmed by IR 1H and 13NMR spectroscopy. Comparison of conjugation and stereochemistry of the respective derivatives showed similar characteristics compared to ones with some higher degree of conjugation in the ferrocenyl series. Comparison of logP of the ferrocenyl derivatives determined by a validated RP-TLC method showed the ferrocenyl derivatives to have higher logPTLC. The results demonstrate that the differences in three dimensional shape, conjugation and lipophilicity do not have strong influence on the P388 cytotoxicity of the investigated phenyl (1−5) and ferrocenyl (6−10) enones.

Synthesis and Characterization of a Series of Ferrocenylfulvenes

Abstract Two new ferrocene-containing benzofulvenes have been prepared and characterized. Some of their physical and spectral properties are described and compared to the unsubstituted ferrocenylfulvene parent.

Ferrocenalrhodanine: A Biologically Active Metallocene Derivative

Abstract A synthesis of a ferrocene-containing rhodanine compound is described. It demonstrates biological activity in certain herbicide screens.