Jordaan Maryam A, Singh Parvesh, Martincigh Bice S
School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban 4000, South Africa.
School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Private Bag X54001, Durban 4000, South Africa.
Spectrochim Acta A Mol Biomol Spectrosc. 2016 Mar 15;157:204-210. doi: 10.1016/j.saa.2015.12.008. Epub 2015 Dec 8.
Efavirenz, commercially known as Sustiva® or Stocrin®, is a first-line antiretroviral treatment for HIV/AIDS. The clinical efficacy of efavirenz is, however, hindered by its solubility. We sought to investigate the solute-solvent effects of efavirenz by means of a combined qualitative study implementing UV-visible spectrophotometry, (1)H NMR spectroscopy and time-dependent density functional theory (TD-DFT) calculations. The UV spectrum displayed two main absorbance maxima, band I and band II at 246-260 and 291-295 nm, respectively. A general bathochromic shift was noticed from the non-polar solvent cyclohexane to the most polar solvent DMSO (≈13.69 nm) in band I and a smaller bathochromic (≈2.17 nm) and hyperchromic shift was observed in band II. We propose that these observations are due to the role of the amino (NH) and carbonyl (CO) functionalities which induce charge-transfer and intra- and inter-molecular hydrogen bonding. The aromatic and amine protons showed the most deshielded effects in the observed chemical shifts (δ) in the more polar DMSO-d6 solvent relative to CDCl3. The (1)H NMR chemical shifts observed are due to the increased delocalization of the lone pair electrons of the amino nitrogen with increased polarity of the more polar DMSO solvent. The theoretical reproduction of the UV and (1)H NMR spectra by means of TD-DFT is in good agreement with the experimental results.
依法韦仑，商品名为苏息拉（Sustiva®）或施多宁（Stocrin®），是一种用于治疗艾滋病毒/艾滋病的一线抗逆转录病毒药物。然而，依法韦仑的临床疗效受到其溶解度的限制。我们试图通过结合紫外可见分光光度法、核磁共振氢谱（¹H NMR）和含时密度泛函理论（TD-DFT）计算的定性研究来探究依法韦仑的溶质-溶剂效应。紫外光谱显示出两个主要吸收峰，I带和II带，分别位于246 - 260纳米和291 - 295纳米处。在I带中，从非极性溶剂环己烷到极性最强的溶剂二甲基亚砜（DMSO）观察到一个普遍的红移（约13.69纳米），而在II带中观察到较小的红移（约2.17纳米）和增色效应。我们认为这些观察结果是由于氨基（NH）和羰基（CO）官能团的作用，它们诱导了电荷转移以及分子内和分子间的氢键形成。相对于氯仿（CDCl₃），在极性更强的二甲基亚砜-d6（DMSO-d6）溶剂中观察到的化学位移（δ）中，芳族质子和胺基质子显示出最大的去屏蔽效应。观察到的¹H NMR化学位移是由于随着极性更强的DMSO溶剂极性增加，氨基氮孤对电子的离域增加所致。通过TD-DFT对紫外光谱和¹H NMR光谱进行的理论再现与实验结果吻合良好。
