Department of Counterfeit Medicinal Products and Drugs, National Medicines Institute, Chełmska 30/34, 00-725, Warsaw, Poland.
Department of Counterfeit Medicinal Products and Drugs, National Medicines Institute, Chełmska 30/34, 00-725, Warsaw, Poland.
J Pharm Biomed Anal. 2019 May 30;169:170-180. doi: 10.1016/j.jpba.2019.02.031. Epub 2019 Feb 23.
NMR spectroscopy is used to investigate the host-guest complexation of (R)-tedizolid, such as tedizolid with the hydroxymethyl substituent at the C5 position of the oxazolidinone ring ((R)-TED) or tedizolid with 5-methyl dihydrogen phosphate ((R)-TED-PO) with heptakis-(2,3-diacetyl-6-sulfo)-β-cyclodextrin (HDAS-β-CD), β-CD and γ-CD, in particular to obtain information about the mode and strength of the guest complexation into the hydrophobic cavity of the host. The complex stoichiometries of 1:1 (host:guest) and 1:2 were detected in millimolar concentrations for HDAS-β-CD and γ-CD with TED-PO complexes, respectively. In the meantime, the mixed of complexes with stoichiometries of 1:1 and 2:1 were found for β-CD with both TED and TED-PO, however the 1:1 complex had a significant advantage.The binding mode was proposed. The estimated binding constants K of the complexes of TED or TED-PO with CDs differ significantly in the order HDAS-β-CD<<β-CD<<γ-CD.
NMR 光谱用于研究（R）-替加环素的主体-客体络合作用，例如替加环素与恶唑烷酮环的 C5 位的羟甲基取代基（（R）-TED）或与 5-甲基二氢磷酸酯（（R）-TED-PO）与七（2,3-二乙酰基-6-磺酸基）-β-环糊精（HDAS-β-CD）、β-CD 和 γ-CD 的络合，特别是为了获得关于客体络合进入主体疏水性腔的方式和强度的信息。在毫摩尔浓度下，分别检测到 HDAS-β-CD 和 γ-CD 与 TED-PO 配合物的 1:1（主体：客体）和 1:2 的配合物化学计量比。同时，对于β-CD 与 TED 和 TED-PO 的配合物，发现了化学计量比为 1:1 和 2:1 的混合配合物，但 1:1 配合物具有明显的优势。提出了结合模式。与 CDs 形成的 TED 或 TED-PO 配合物的估计结合常数 K 的顺序为 HDAS-β-CD<<β-CD<<γ-CD，差异非常显著。
