Thionitroxides, RSNHO*: the structure of the SNO moiety in "S-Nitrosohemoglobin", a possible NO reservoir and transporter

Abstract

Nitric oxide (NO) plays important roles in many biological processes. S-Nitrosothiols have long been believed to have significant roles in NO biochemistry. The modified cysteine residue of hemoglobin was previously identified as a distorted S-nitrosothiol (RSNO) or an S-hydroxyamino radical (RSN*OH). Here we show that a thionitroxide (RSNHO*, S-aminyloxyl radical) is likely the observed species. Computational studies show that the thionitroxide is the only structure consistent with the electron density in the hemoglobin Cysbeta93-SNO structure previously reported. Although a metastable adduct, the thionitroxide in a hydrogen-bonding environment can form readily and release NO upon exposure to an aqueous environment. The thionitroxides could be responsible for the biological effects attributed to S-nitrosothiols or could serve as precursors to S-nitrosothiols in oxidative conditions.

Figure 1

The crystallographic C-S-N-O structures in purported S-nitroso-hemoglobin (distances in angstrom, unexpected dihedral angles in red).

Figure 2

Rotational energy profiles of RSNO, RS-NH-O·, RS-N·-OH, and RS-NH-OH (R = Me) with the B3LYP/6-31+G* method (two dashed lines stand for the dihedral angles of the observed SNO species in the proteins), and the CBS-QB3 calculated global minima of cis-RSNO (1), trans-RSNO (2), RS-N·-OH (3), RS-NH-O· (4), and RS-NH-OH (5), and rotational transition states for RSNO (6^≠) and RS-N·-OH (7^≠).