15N NMR and crystal structure studies of 5-(2-pyridylmethylene)pseudothiohydantoin;† dipolar dephasing experiments for establishing the preferred tautomer in the solid and solution states

Abstract

The preferred tautomeric form of 5-(2-pyridylmethylene)pseudothiohydantoin 1 in the solid and solution states has been determined by natural abundance high-resolution 15 N NMR studies and by a single crystal X-ray structural analysis.

Experimental and computational study of the energetics of hydantoin and 2-thiohydantoin

“…Our results are in a very good agreement with the experimental observations of several hydantoin and 2-thiohydantoin derivatives [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61].…”

Serendipitous Discovery of a Potent Influenza Virus A Neuraminidase Inhibitor

“…Close examination of the N8-6 complex indicates that the sulfur and amine nitrogen of the spirolactam moiety lie out of plane with the other ring atoms, forming a separate plane with the amide nitrogen. Consistent with structures from crystallographic analysis of other thiazolidones, [17] this conformation would suggest that compound 6 exists predominantly in the form of a zwitterionic resonance contributor 6 c when bound in the enzyme active site, favoring hydrogen-bonding interactions between the iminium nitrogen and an acidic pocket comprised of E119, E227, E277, and the main-chain carbonyl of W178 (Figure 1 a). This compound is likely to be held in this zwitterionic resonance state for three reasons: 1) interactions between the iminium nitrogen and the acidic patch stabilizing the positive charge, 2) the proximity of the D151 side chain to the lactam carbonyl which would electrostatically disfavor charge build up at this carbonyl oxygen atom, and 3) a water-mediated hydrogen bond stabilizing the negative charge on the amide nitrogen.…”

NMR Spectroscopic Study of Tautomerism in Solution and in the Solid State

“…This enables quantification of the tautomeric forms by examining δ (H-11), δ(C-11), and δ(N-1) in CDCl 3 solution NMR spectra as well as calculation of both the temperature-dependent equilibrium constants K T and the free energy differences G • T of the tautomers [56]. (25b) is preferred [57]. The 15 N resonances at 68, −160, and −266 ppm were unambiguously assigned to N-8, N-3, and N-2, respectively, by comparison with similar compounds.…”

“…The 15 N resonances at 68, −160, and −266 ppm were unambiguously assigned to N-8, N-3, and N-2, respectively, by comparison with similar compounds. Dipolar dephasing experiments were employed to distinguish between protonated and nonprotonated 15 N nuclei, and in solution no proton correlation was observed for N-3 [57]. The exchange rates k (s −1 ) of the imine-amine tautomerism of a variety of guanidine sugars 26 (Scheme 5.20) were calculated from the intensity ratios of diagonal and exchange cross peaks (r) of a series of 2D-ROESY spectra with different mixing times t m [s] [ln(r + 1)/(r − 1)) = k t m ] [58].…”