α-Hydrogen Abstraction by •OH and •SH Radicals from Amino Acids and Their Peptide Derivatives

Abstract

We have used computational quantum chemistry to investigate the thermochemistry of α-hydrogen abstraction from the full set of amino acids normally found in proteins, as well as their peptide forms, by •OH and •SH radicals. These reactions, with their reasonable complexity in the electronic structure (at the α-carbon), are chosen as a consistent set of models for conducting a fairly robust assessment of theoretical procedures. Our benchmarking investigation shows that, in general, the performance for the various classes of theoretical methods improves in the order nonhybrid DFT → hybrid DFT → double-hybrid DFT → composite procedures. More specifically, we find that the DSD-PBE-P86 double-hybrid DFT procedure yields the best agreement with our high-level W1X-2 vibrationless barriers and reaction energies for this particular set of systems. A significant observation is that, when one considers relative instead of absolute values for the vibrationless barriers and reaction energies, even nonhybrid DFT procedures perform fairly well. To exploit this feature in a cost-effective manner, we have examined a number of multilayer schemes for the calculation of reaction energies and barriers for the abstraction reactions. We find that accurate values can be obtained when a "core" of glycine plus the abstracting radical is treated by DSD-PBE-P86, and the substituent effects are evaluated with M06-2X. Inspection of the set of calculated thermochemical data shows that the correlation between the free energy barriers and reaction free energies is strongest when the reactions are either endergonic or nearly thermoneutral.

Reaction of Amino Acids, Di‐ and Tripeptides with the Environmental Oxidant NO3.: A Laser Flash Photolysis and Computational Study

“…with the N ‐ and C‐ protected amino acids, we performed DFT calculations of the potential energy surface. The computations were carried out with the Gaussian 09 program using the BHandHLYP, wB97XD and M06‐2X methods, which have been employed previously to investigate radical‐induced α‐hydrogen abstraction in amino acids . Calculations in acetonitrile were performed for selected reactions using the conductor‐like polarizable continuum model (CPCM) .…”

“…The computations were carriedo ut with the Gaussian09p rogram [29] using the BHandHLYP,w B97XD and M06-2X methods, which have been employed previously to investigate radical-induced a-hydrogen abstraction in amino acids. [30] Calculations in acetonitrile were performed for selected reactions using the conductor-like polarizablec ontinuumm odel (CPCM). [31] All ground and transition structures were verified by vibrational frequency analysis at the same level of theory,a nd all identified transition structures showed only one imaginary frequency.T he spin expectation value, < s 2 > ,was very close to 0.75 after spin annihilation.…”

An ONIOM investigation of the effect of conformation on bond dissociation energies in peptides

“…In a series of studies in recent years, we have also used computational quantum chemistry to examine bond dissociation energies, including some that are biologically relevant . In addition, we have examined reaction barriers for bond dissociation processes that result from radical attack . While our earlier studies did not examine conformational effects in detail, we have recently investigated more thoroughly the qualitative and quantitative effects of conformation on the formation of small peptide radicals .…”

“…[17][18][19][20][21][22] In addition, we have examined reaction barriers for bond dissociation processes that result from radical attack. [23][24][25][26][27] While our earlier studies did not examine conformational effects in detail, we have recently investigated more thoroughly the qualitative and quantitative effects of conformation on the formation of small peptide radicals. [28] In addition, we provided a glimpse of the differences between observations obtained with small models and those that more closely resemble larger peptides.…”

Stability of the chlorinated derivatives of the DNA/RNA nucleobases, purine and pyrimidine toward radical formation via homolytic CCl bond dissociation

“…With the ever increasing computational power of supercomputers and the development of computationally economical composite ab initio methods, [22][23][24] it is possible to obtain highly accurate thermochemical data for biologically relevant molecules such as amino acids and DNA bases (see Refs. [25][26][27][28][29][30][31][32] for some recent studies). In the context of the present study it is important to obtain accurate CACl BDEs for chlorinated DNA bases to establish which carbon-centered radicals are likely to be formed with the greatest ease under certain biochemical conditions.…”