Isomerism of Cycloserine and Its Protonated Form

Abstract

A comprehensive ab initio investigation has been performed on the structure and stability of the isomers of cycloserine and its protonated forms in the unsolvated state. Many conformers of cycloserine in the ketonic (K), enolic (E4 and E2), and zwitterionic (Z7 and Z2) forms have been characterized. Enols E2 are only a few kilocalories per mole less stable than the K isomers. Enols E4, as well as Z7 and Z2 zwitterions, are several tens of kilocalories per mole less stable than K. All the above isomeric structures exhibit pronounced isoxazolidine ring puckering, which generates very rich conformeric landscapes. The relative stability of the conformers of K, E2, and E4 responds essentially to a complex balance between the attractive and repulsive electrostatic interactions among their functional groups. The preferred site of protonation of cycloserine in the gas phase has been also investigated computationally and experimentally by IR multiphoton dissociation (IRMPD) spectroscopy. The most basic center of cycloserine is the N(7) nitrogen atom (proton affinity (PA)=215.3 kcal mol−1). Another important basic site is the O(6) oxygen atom (PA=213.0 kcal mol−1). Their most populated conformers have been identified by IRMPD spectroscopy. Their predominance responds to the electrostatic interactions among the functional groups of the protonated molecule

Retention characteristics of some antibiotic and anti-retroviral compounds in hydrophilic interaction chromatography using isocratic elution, and gradient elution with repeatable partial equilibration

“…It has been shown [13,21,34] that decreasing buffer concentration in HILIC results in reduced retention for neutral compounds, which is thought to be due to decreased thickness of the water layer. Alternatively, increased retention for basic compounds occurs at lower buffer concentration due to reduced competition for ion-exchange interactions [44]. These explanations correlate well with our results above.…”

“…shown [44] that acetonitrile promotes the dimerization of d-cycloserine whereas this reaction is strongly inhibited in methanol. It is thought that methanol protects against nucleophilic attack on the carbonyl group through electrophilic solvation of the α-amino position.…”

Electronic structure and conformational flexibility of d-cycloserine

“…12 Furthermore, for comparative purposes, the twelve optimized conformational geometries and their relative energies were also obtained by the same method as reported in ref. The present MP2 calculations used an improved basis set with respect to our previous work (MP2(fc)/6-311+G**).…”

“…11 Two conformers of D-cycloserine were assumed to predominate in the gas phase, namely III and VII, separated by an energy of 1.1 kcal mol À1 (Fig. 12 Besides III and VII, ten other conformers were identified on the MP2/6-311++G** potential energy surface (PES) of D-cycloserine, some of them being significantly more stable than III and VII (e.g. However, the valence and core ionization spectra, simulated by assuming this binary mixture, did not result in good agreement with the experiment.…”

Real time evolution of unprotected protonated galactosamine probed by IRMPD spectroscopy

“…In the last few years the infrared multiphoton dissociation (IRMPD) technique has been extensively employed to assess the conformations that biological molecules assume in the gas phase. [10][11][12][13][14][15][16][17] In the present work the ESI-IRMPD-MS spectrum of protonated galactosamine (GalNÁH + ) has been measured to determine for the first time the features of unprotected a-GalNÁH + and b-GalNÁH + anomers. Their conformational landscape includes four main degrees of freedom: (1) the position of the 1 C 4 " 4 C 1 chair equilibria (Fig.…”