Theor Chem Acc (2007) 117:145–152 DOI 10.1007/s00214-006-0164-7 REGULAR ARTICLE Isomerization reactions of RSNO (R=H, C n H 2n+1 n ≤ 4) Chin-Hung Lai · Elise Y. Li · Pi-Tai Chou Received: 21 March 2006 / Accepted: 2 June 2006 / Published online: 23 August 2006 © Springer-Verlag 2006 Abstract We have applied various theoretical meth- ods to gain detailed insights into the isomers as well as the transition states (TSs) along the corresponding reac- tion pathways for RSNO (R=H, C n H 2n+1 n ≤ 4). On the basis of G2 and G2MP2 results, the relative order of stability for R=H is estimated to be trans-HSNO > cis- HSNO > HNSO > cis-HONS ≈ trans-HONS, while it is cis-CH 3 SNO ≈ trans-CH 3 SNO > CH 3 NSO > trans- CH 3 ONS > cis-CH 3 ONS for R=CH 3 . A similar trend is also obtained from the B3P86 method with consid- erably less computing effort if the nearly isoenergetic isomers cis-HONS and trans-HONS are ignored. Based on the results of B3P86, cis-RSNO is more stable than trans-RSNO when R=H is replaced by alkyl groups ex- cept for R=t-Bu. Natural bond orbital analyses allow us to explore whether the high reactivity of S-nitros- othiols is due to the strong negative hyperconjugation (n π O ↔ σ ∗ N-S ). The mesomeric effect of S-nitrosothi- ols, although non-negligible, does not cause the break- age of N–O bond due to the compensation of columbic attraction between N and O. Keywords RSNO · G2 · B3P86 · Negative hyperconjugation · Mesomeric effect Electronic supplementary material Supplementary material is available to authorised users in the online version of this article at http://dx.doi.org/10.1007/s00214-006-0164-7 . C.-H. Lai (B ) · E. Y. Li · P.-T. Chou Department of Chemistry, National Taiwan University, 106, Taipei, Taiwan, R.O.C. e-mail: chinhunglai@ntu.edu.tw P. -T. Chou e-mail: chop@ntu.edu.tw 1 Introduction S-nitrosothiols (RSNOs) have attracted much attention because species containing an -SNO functional group have been found in vivo as part of the metabolism of nitric oxide (NO), [1–3] an important biological messen- ger. For a long time, the S-nitrosothiols have been pro- posed to play a key role in transporting and storing NO within the organism [1–6]. The S-nitrosothiols also ex- hibit many biological properties similar to those of NO, including vasodilatation of arteries, inhibition of plate- let aggregation, smooth muscle cell proliferation, etc. [5,7–11]. Furthermore, the derivatives of S-nitrosothi- ols, with a form of S-nitrosate cysteine thiols, were found to be involved in Zn 2+ complexation to disrupt cys- teine–Zn 2+ linkages via a transnitrosation mechanism [12–17]. Unfortunately, the S-nitrosothiols (RSNOs) readily release NO • via thermal agitation [18], radiation [19–21], or reactions catalyzed by certain metal ions [22– 33], superoxide [34, 35] and seleno compounds [36]. Al- though the heterolytic cleavage might as well take place, the biological activity of RSNOs has been mostly attrib- uted to the homolytic cleavage of the S–NO bond with the release of NO • [37]. Accordingly, experimental ap- proaches on the RSNOs are rare [38, 39], and our current understanding on the physical and chemical properties of this important class of biomolecules is still unsatisfac- tory. Alternatively, computational chemistry seems to of- fer a reasonable access to investigate the reaction path- ways of RSNOs. Houk and others have performed some calculations to probe the bond dissociation energy of the N–S bond as well as the energetics of trans–cis con- formers [40–43]. In a study of primarily photolyzing cis-HSNO, forming the unexpected trans-HONS,