Understanding the Role of pH in Protein‐Haptenation Reaction: Kinetics and Mechanisms of the Protein‐Haptenation Reactions of Selected Quinones Present in the Environment

Abstract

There are several xenobiotics (allergens) in the environment which may induce allergic contact dermatitis (ACD), an occupational and environmental health disease. This health disease is of global concern because it has no cure and can only be managed in affected individuals by preventing them from further exposure to these allergens. The following quinones (Q) are known to be air pollutants: 1,2‐naphthoquinone (1,2‐NQ), 1,4‐naphthoquinone (1,4‐NQ), 9,10‐phenanthraquinone (PQ), and 9,10‐anthraquinone (AQ). There have been studies on the cytotoxicity of these air pollutants, but no kinetic studies have been carried out on them to determine their chemical reactivity and, more especially, their interaction with model proteins so as to ascertain if they can react with skin proteins thereby causing allergic reactions. This article provides details on the kinetics studies carried out on the protein‐haptenation reactions of these quinones with 4‐nitrobenzenethiol (NBT), a model nucleophile, as well as the mechanisms of their reactions. The NBT−Q reactions were investigated under pseudo‐first‐order conditions at various concentration ratios at a temperature of 25 °C at three different pH values by either ultraviolet‐visible (UV‐Vis) or stopped‐flow spectrophotometry, as appropriate. The reaction rate constants obtained for the NBT−Q reactions were in the following order: at pH 7.42: 1,2‐NQ>1,4‐NQ>PQ>AQ while at pH 5.65, the order was observed to be 1,2‐NQ>1,4‐NQ>PQ>AQ and at pH 8.41, it was 1,4‐NQ>PQ>AQ>1,2‐NQ. These trends for the reaction rate constants of the Q at the three pH values can be attributed to inductive effects and the position of oxo‐groups on the phenyl rings. The NBT−Q reactions were further investigated by determining the effect of ionic strength on the reaction rate constants with potassium sulphate as the background electrolyte. Our findings showed that there are no charged species at the transition state of the NBT−Q reactions. The products of the NBT−Q reactions were isolated and characterized by means of UV‐Vis and FTIR spectrophotometry and NMR and TOF‐MS spectrometry. The deduced mechanisms for the NBT−Q reactions were validated by computer simulation with “Simkine3” software.