A Stable Aminothioketyl Radical in the Gas Phase

Abstract

We report the first preparation of a stable aminothioketyl radical, CH(3)C(•)(SH)NHCH(3) (1), by fast electron transfer to protonated thioacetamide in the gas phase. The radical was characterized by neutralization-reionization mass spectrometry and ab initio calculations at high levels of theory. The unimolecular dissociations of 1 were elucidated with deuterium-labeled radicals CH(3)C(•)(SD)NHCH(3) (1a), CH(3)C(•)(SH)NDCH(3) (1b), CH(3)C(•)(SH)NHCD(3) (1c), and CD(3)C(•)(SH)NHCH(3) (1d). The main dissociations of 1 were a highly specific loss of the thiol H atom and a specific loss of the N-methyl group, which were competitive on the potential energy surface of the ground electronic state of the radical. RRKM calculations on the CCSD(T)/aug-cc-pVTZ potential energy surface indicated that the cleavage of the S-H bond in 1 dominated at low internal energies, E(int)< 232 kJ mol(-1). The cleavage of the N-CH(3) bond was calculated to prevail at higher internal energies. Loss of the thiol hydrogen atom can be further enhanced by dissociations originating from the B excited state of 1 when accessed by vertical electron transfer. Hydrogen atom addition to the thioamide sulfur atom is calculated to have an extremely low activation energy that may enable the thioamide group to function as a hydrogen atom trap in peptide radicals. The electronic properties and reactivity of the simple aminothioketyl radical reported here may be extrapolated and applied to elucidate the chemistry of thioxopeptide radicals and cation radicals of interest to protein structure studies.

Perturbing Peptide Cation-Radical Electronic States by Thioxoamide Groups: Formation, Dissociations, and Energetics of Thioxopeptide Cation-Radicals

“…Tautomers in which one proton was placed on the thioxoamide sulfur atom rearranged by spontaneous proton transfer to the N-terminus. Note that the intrinsic proton affinity of the thioxoamide group, which was calculated as PA = 909 kJ mol –1 for N -methylthioacetamide, is slightly higher than the intrinsic basicities of Gly or Ala residues (886–900 kJ mol –1 ) . The preferential protonation at the N-terminus in GtK, AtK, and AtR may be due to the σ-electron donating effect of the thioxoamide group, increasing the amino group basicity, and Coulomb repulsion with the Lys or Arg charge that presumably destabilizes the S-protonated tautomers because of a shorter distance between the charge sites.…”

“…11 We have recently reported a joint experimental and computational study of an aminothioketyl radical produced by hydrogen atom addition to N-methylthioacetamide. 12 The energetics and dissociations of this radical system showed some analogies with those of Nmethylacetaminoketyl radical, which is a prototypical peptide radical model. 13 Here, we extend these studies to cation-radicals derived from electron−ion recombination of doubly protonated thioxopeptides Gly-thio-Lys, Ala-thio-Lys, and Ala-thio-Arg.…”

“…Nevertheless, the effects on ExD of peptide structure variations are best explored by well-designed experiments . We have recently reported a joint experimental and computational study of an aminothioketyl radical produced by hydrogen atom addition to N -methylthioacetamide . The energetics and dissociations of this radical system showed some analogies with those of N -methylacetaminoketyl radical, which is a prototypical peptide radical model .…”