Exploring the redox mechanism of 9-acridinyl amino acid derivatives by electrochemical and theoretical approach

Abstract

Investigating and understanding the redox characteristics of potential anticancer agents is of great importance, as these properties are the key factor in the anticancer potential of drugs and can impact the mechanism of action, stability, metabolism, and selectivity of the drug toward cancer cells. Four compounds, previously confirmed to possess notable in vitro anticancer activity and the ability to interact with DNA, were subjected to a detailed electrochemical study. These are 9-acridinyl amino acid derivatives (9R-A), which were investigated in this study using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) with a glassy carbon electrode. The effects of pH (ranging from pH 2–9) and scan rate were thoroughly examined. The findings revealed that three independent oxidation and reduction processes occurred, all of which were diffusion-controlled. Two electroactive regions of the molecule contribute to these redox processes: the nitrogen (N10) of the acridine ring and the enamine nitrogen (N11) in the derivative’s side chain. In 9R-A, the acridine ring undergoes a two-electron oxidation: first forming a monomeric radical cation that dimerizes, then undergoing a second electron transfer to yield a new radical cation. The reduction mechanism similarly involves a two-electron transfer, producing a monomeric radical that dimerizes and later forms a new radical. A significant factor in the redox behavior of 9-acridinyl amino acid derivatives is the presence of a secondary amine in the side-chain substituent. This amine undergoes oxidation via the loss of a single electron, resulting in the formation of a monomeric radical cation that is stabilized through deprotonation. While the oxidation mechanism appears to be consistent across all four 9R-A derivatives, differences in their oxidation affinity arise due to structural variations in the side-chain substituents. The experimental electrochemical findings were further supported by computational chemistry. Quantum chemical parameter evaluations provide deeper insights into the oxidation and reduction mechanisms, particularly in relation to the influence of substituents on these processes.