σ-Complexes as biochemical and biophysical probes. Part 6. The interaction of N-2,4,6-trinitrophenyl-L-lysine with methoxide ion in dimethylsulfoxide-methanol (95%-5% v/v) mixture: proton transfer and σ-complex formation

Ikenna Onyido,Erwin Buncel,Masashi Hamaguchi,Christian V Stevens

doi:10.3998/ark.5550190.0004.c18

Abstract

The interaction of N-2,4,6-trinitrophenyl-L-lysine as the hydrochloride salt, 1, with methoxide ion in dimethyl sulfoxide-methanol (DMSO-MeOH, 95/5, v/v) mixture has been investigated using UV-visible spectrophotometry at 25 o C. An initial 1:1 interaction between MeO - and 1 results in the rapid and reversible deprotonation of N(1)-H while a 2:1 interaction involves the rapid transfer of a proton from NH3 + to the base. Deprotonation of N(1)-H in 1 is thus the kinetically and thermodynamically preferred process. At mole ratios MeO - :1 being > 3, addition of the MeO - nucleophile to the C-3 position of the doubly deprotonated substrate generates a σadduct. The order of acidity: N(1)-H > NH3 + > COOH which emerges in 1 is attributed to characteristic solute-solvent interactions involving delocalized anions in the DMSO-MeOH solvent mixture. The significance of the inversion of acid strengths observed in this study, in relation to general acid-base catalysis by protein residues in the non-aqueous environment of enzyme active sites in biological systems, is highlighted.

Highlights

Our continuing interest in σ -complexes of the Meisenheimer type, formed in the interactions of nitroaromatic compounds with bases, derives in part from the biological relevance and mechanistic significance ascribed to them.[1,2,3] For example, the anti-leukemic activity of certain nitrobenzofurazan and nitrobenzofuroxan derivatives has been linked to the σ -complexes derived in the interaction of these compounds with intracellular thiol groups.[4]
We have previously reported on the interactions of methoxide ion with N-methylpicramide (NMP)[13], N,N-dimethylpicramide (DMP)[14], N-picrylethylenediamine (PED) as its HCl salt[15], and N,N-dimethyl-picrylethylenediamine (DPED)[16] in dimethyl sulfoxide (DMSO)-methanol (MeOH) mixtures
Reaction pathways This study has revealed a number of spectral species that are formed consecutively in the DMSO-MeOH system

Summary

Introduction

Our continuing interest in σ -complexes of the Meisenheimer type, formed in the interactions of nitroaromatic compounds with bases, derives in part from the biological relevance and mechanistic significance ascribed to them.[1,2,3] For example, the anti-leukemic activity of certain nitrobenzofurazan and nitrobenzofuroxan derivatives has been linked to the σ -complexes derived in the interaction of these compounds with intracellular thiol groups.[4]. Dry DMSO, the reaction of 1 with 1,4-diazabicyclo[2.2.2]octane (DABCO) resulted in the conversion of 1 to the species X; the final spectrum generated is identical to that obtained with NaOMe, showing an absorption maximum at 443 nm and shoulder with mid-point at 492 nm.

Results

Conclusion