Boros Miklós, Kökösi József, Vámos József, Noszál Béla
Semmelweis University, Department of Pharmaceutical Chemistry, Hogyes E. u. 9, Budapest 1092, Hungary.
J Pharm Biomed Anal. 2007 Mar 12;43(4):1306-14. doi: 10.1016/j.jpba.2006.10.040. Epub 2006 Dec 11.
Protonation equilibria of N-methyl-D-aspartate (NMDA, a specific glutamate receptor agonist) and its derivatives are characterized at the macroscopic and microscopic levels. (1)H NMR-pH and pH-potentiometric titrations were carried out to determine the macroconstants. Microconstants were obtained by appropriate combination of acidity and NMR parameters of the parent compound and its three synthetic derivatives. These derivatives were close models of the NMDA minor microspecies, allowing the calculation of all the 12 microconstants, the 8 microspecies concentrations and 3 site interactivity parameters. Reliability of the microconstants was assessed by three independent test methods. It was found that protonation of the secondary amino site decreases the beta- and alpha-carboxylate basicities almost exactly by one and two orders of magnitude, respectively, whereas protonation of one of the carboxylates lessens the basicity of the other one by a factor of 3. NMR-pH profiles, macro- and microscopic protonation schemes and species-specific distribution diagrams are presented.
N-甲基-D-天冬氨酸（NMDA，一种特定的谷氨酸受体激动剂）及其衍生物的质子化平衡在宏观和微观层面进行了表征。进行了¹H NMR-pH和pH电位滴定以确定宏观常数。通过母体化合物及其三种合成衍生物的酸度和NMR参数的适当组合获得微观常数。这些衍生物是NMDA次要微观物种的近似模型，从而能够计算所有12个微观常数、8种微观物种浓度和3个位点相互作用参数。通过三种独立的测试方法评估微观常数的可靠性。结果发现，仲氨基位点的质子化分别使β-和α-羧酸盐的碱度几乎恰好降低一个和两个数量级，而其中一个羧酸盐的质子化使另一个羧酸盐的碱度降低3倍。给出了NMR-pH曲线、宏观和微观质子化方案以及物种特异性分布图。
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