Bednarek Elzbieta, Bocian Wojciech, Michalska Katarzyna
Nuclear Magnetic Resonance Laboratory, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland.
J Chromatogr A. 2008 Jun 6;1193(1-2):164-71. doi: 10.1016/j.chroma.2008.04.008. Epub 2008 Apr 11.
NMR study and molecular modeling were performed to improve the level of understanding of the chiral recognition process occurring between linezolid and anionic single-isomer cyclodextrin-heptakis-(2,3-diacetyl-6-sulfato)-beta-cyclodextrin (HDAS-beta-CD). NMR spectrometry allowed to estimate the stoichiometry of the complexes between HDAS-beta-CD and S- or R-linezolid and to determine the binding constants. The 1:1 complex stoichiometry was detected in millimolar concentrations and the mode of binding was proposed. The binding constants Ka of the complexes were of the order of 30-80 M(-1). Molecular dynamic simulations of 40ns for four complexes and calculations of binding free energies were performed. These calculations allowed determining the mode of binding of linezolid to HDAS-beta-CD and explaining the binding enantioselectivity.
进行了核磁共振（NMR）研究和分子建模，以提高对利奈唑胺与阴离子单异构体环糊精 - 七 -（2,3 - 二乙酰基 - 6 - 硫酸根）-β-环糊精（HDAS - β - CD）之间发生的手性识别过程的理解水平。核磁共振光谱法能够估计HDAS - β - CD与S - 或R - 利奈唑胺之间复合物的化学计量，并确定结合常数。在毫摩尔浓度下检测到1:1的复合物化学计量，并提出了结合模式。复合物的结合常数Ka约为30 - 80 M⁻¹。对四种复合物进行了40纳秒的分子动力学模拟并计算了结合自由能。这些计算能够确定利奈唑胺与HDAS - β - CD的结合模式，并解释结合对映选择性。
