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O processo de biorredução enzimática do grupo nitro é de grande importância para a ação molecular de nitrocompostos aromáticos biologicamente ativos. Os métodos eletroquímicos são considerados ferramentas úteis para a simulação de processos metabólicos in vivo. No presente trabalho, realizaram-se estudos eletroquímicos em meio aprótico (N,N-dimetilformamida (DMF) mais perclorato de tetrabutilamônio (TBAP) 0,1 mol L -1 ) utilizando-se as técnicas de voltametria cíclica (CV), de pulso diferencial (DPV) e de onda quadrada (SWV) de 12 adutos de Morita-Baylis-Hillman (MBHA) com atividade leishmanicida significativa. Para facilitar a análise, os adutos foram agrupados em quatro classes de acordo com a cadeia lateral. Os estudos de CV evidenciam duas ondas referentes à redução do grupo nitro e uma ou duas outras ondas (em potencial mais negativo) relativas à redução da função carbonila α,β-insaturada ou da olefina ativada por grupos nitrila. Adutos orto-substituídos apresentam maior facilidade de redução quando comparados aos demais isômeros (meta e para) em função, provavelmente, da ligação de hidrogênio entre o grupo nitro e a hidroxila benzílica, o que estabiliza mais o produto eletrogerado do que o composto de partida. Derivados orto também mostram uma maior atividade leishmanicida em comparação com seus isômeros em cada série. Estudos conformacionais usando HF/6-31+G(d)/PCM como nível de cálculo evidenciaram este efeito. Valores calculados de dureza molecular (N) e de cargas atômicas (Q N ) explicam corretamente os dados experimentais obtidos.Enzymatic bioreduction of nitro groups plays an important role on the activity of biologically active nitroaromatic compounds. Electrochemical methods are useful tools to simulate in vivo metabolic processes. This work presents electrochemical studies in aprotic media (N,N-dimethylformamide (DMF) plus tetrabutylammonium perchlorate (TBAP) 0.1 mol L -1 ) using cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV) of twelve Morita-Baylis-Hillman adducts (MBHA) with significant leishmanicidal activity. To facilitate the analysis, the molecules were grouped in four classes according to the side chain. CV studies show three up to four reduction waves, in which the first two waves are related to nitro group reduction. The other waves (presenting more negative potential) refer to the reduction of the α,β-unsaturated carbonyl or to the nitrile activated olefin side-chain. Ortho adducts present facilitated reduction in comparison to the other isomers (meta and para) possibly due to hydrogen bond formation between the benzylic-OH and the nitro group, which stabilizes the reduction product (anion radical nitro) more efficiently than the original compound. Ortho derivatives also present higher leishmanicidal activity upon comparison to the other derivatives of each class. Conformational studies using HF/6-31+G(d)/PCM as a calculation level highlight this effect. Molecular hardness (N) and atomic charges (Q N ) values corroborate the obtained expe...

Electrochemical methods are considered useful tools for simulations of biological redox reactions. The activities of quinones depend on their bioreduction. Biologically active pterocarpanquinones LQB-149 (nitroderivative), 150 and 151 (bromo and chloroderivatives, respectively) were electrochemically investigated by cyclic voltammetry, differential pulse voltammetry, and in situ UV-Vis spectroelectrochemistry, in aprotic media (N,N-dimethylformamide (DMF) + tetra-N-butylammonium (TBAPF 6)). The data obtained regarding their reduction mechanisms, positive reactivity with oxygen and analysis of the electrogenerated intermediates were useful in explaining their biological outcomes. The appearance of bands at 397 and 480 nm, for the halogenated compounds, suggests the generation of transient quinonemethides (QM), electrophilic intermediates related to their activity. As an additional proof for the intermediacy of QM, in the redox processes, chemical reduction of LQB-150, in the presence of hexanethiol was performed and led to a thioalkylated quinone. For the nitroderivative, a broad band appeared at 432 nm, corresponding to the generation of the nitroradical anion, giving rise to a dianion diradical, after reduction at the second wave potential. Computational data correlate well with electrochemical experiments. Homogeneous electron transfer to oxygen, yielding reactive oxygen species, the generation of electrophilic species and the radical reactivity, explain partially the mechanism of biological action.