Theoretical study of substituent effects in the unimolecular decomposition of N-chloro-?-amino acid anions. Analysis of transition structure and molecular reaction mechanism

Abstract

The unimolecular decomposition of substituted N-chloro-a-glycine anions was examined by an ab initio method using the 6-31G* basis set to obtain an insight into the relationship between transition-state structure and reactivity. The complete potential energy surface was explored and the stationary points corresponding to reactant and transition structure were localized. A reaction analysis by correlation of bond orders revealed that the reaction mechanism corresponds to an asynchronous fragmentation. The transition structure for all the compounds has an antiperiplanar conformation between the C-C and N-CI bond breaking and it has a product-like character. The influence of the substitution on the a-carbon and on the nitrogen is discussed. When the size and number of substituents on the a-carbon and to a lesser extent on the nitrogen atom increase the relative energy decreases. The size of the substituent produces perpendicular effects and the type and number of substituents give parallel effects.Several studies have been carried out in order to establish the nature of the molecular mechanisms for the decomposition of these Fox and Bullock4 put forward a two-step mechanism: initial loss of the a-

Degradation Mechanisms and Substituent Effects of N-Chloro-α-Amino Acids: A Computational Study

“…N -Chloro-α-amino acids form not only in the disinfection of water or wastewater with chlorine but also in living organisms and are associated with the presence of hypochlorous acid (HOCl) in response to the destruction of invading pathogens. − As a subclass of nitrogenous disinfection byproducts ( N -DBPs), N -chloro-α-amino acids generally have higher cytotoxicity, genotoxicity, and mutagenicity than those of the currently regulated DBPs. − Moreover, decomposition products of N -chloro-α-amino acids have been reported to have not only odor problems but also potential health risks to humans. − Therefore, N -chloro-α-amino acids have attracted extensive attention for decades in both environmental and physiological fields. − …”

“…However, to the best of our knowledge, there has been a limited understanding of their degradation mechanisms. Most studies − have concentrated on the unimolecular decomposition of N -monochloro-α-amino acids and reported that they generally degrade into amines, carbonyl products, chloride ions, and carbon dioxide via the concerted Grob fragmentation (CGF) mechanism in neutral aqueous solution. Although such unimolecular decomposition has been accepted as an asynchronous concerted process, − the activation barriers calculated from the theoretical studies dramatically varied with different ab initio and DFT methods.…”

“…Most studies − have concentrated on the unimolecular decomposition of N -monochloro-α-amino acids and reported that they generally degrade into amines, carbonyl products, chloride ions, and carbon dioxide via the concerted Grob fragmentation (CGF) mechanism in neutral aqueous solution. Although such unimolecular decomposition has been accepted as an asynchronous concerted process, − the activation barriers calculated from the theoretical studies dramatically varied with different ab initio and DFT methods. For example, for the degradation of N -monochloro-glycine ( N -Cl-Gly), the activation barriers calculated using ab initio methods with correlations and DFT methods are in the range of 10–45 and 1–4 kcal/mol, respectively, − which are apparently inconsistent with the experimental rate constant k of ∼10 –6 s –1 . , Unfortunately, to date no reasonable theoretical results regarding this system have been obtained.…”

“…Furthermore, it is interesting to discover that the rate constants for various N -monochloro-α-amino acids, whose substituents are mainly alkyl groups, are highly dependent on the number of substituents on the α-carbon and N -terminal sites but independent of the size. − ,− Except for the alkyl group, the effects of other substituents on the rate constants and the underlying reasons are unclear. In addition, very recent research work , has demonstrated that degradations of N -Cl-Gly and N -monochloro-α-alanine ( N -Cl-Ala) are both pH-dependent in the pH range of 7–13, and glyoxylate and pyruvate ions are generated in a pH range of 12–13 for N -Cl-Gly and N -Cl-Ala, respectively.…”

“…To answer the above questions, in this work, glycine, alanine, and valine were chosen as model amino acids, and the degradation mechanisms of these N -chloro-α-amino acid anions under neutral and base-promoted conditions have been investigated. Compared with the earlier studies, − in addition to the unimolecular decomposition mechanism, the elimination mechanism has also been studied here. To extensively explore the substituent effects, more real amino acids including serine, sarcosine, 2-amino butyric acid, 2-amino isobutyric acid, and some designed model amino acids have been chosen, and the key degradation reactions of their corresponding N -chloro-α-amino acid anions have been performed.…”