Chourpa I, Beljebbar A, Sockalingum G D, Riou J F, Manfait M
UFR de Pharmacie, Université de Reims Champagne-Ardenne, France.
Biochim Biophys Acta. 1997 Mar 15;1334(2-3):349-60. doi: 10.1016/s0304-4165(96)00113-4.
Lactone and carboxylate forms of potent antitumor agents, camptothecins (CPTs) have been studied by Raman, Fourier-transform Raman (FT-Raman) and surface-enhanced Raman scattering (SERS) spectroscopy. Similarity of the Raman spectra of CPTs with corresponding FT-Raman spectra in the near-infrared allowed the latter to be compared with their SERS counterparts in order to analyse the interaction of the drugs with silver colloids. Different types of silver colloids (reduced with sodium borohydride or sodium citrate, with or without activation by anions) have been evaluated. Citrate-reduced colloid, activated with chloride anions (CAS) has been found to be the best compromise for SERS studies of both forms of CPTs. We suggest that in general CPTs are adsorbed on CAS via the nitrogen in ring B and are more inclined to a flat orientation than to a perpendicular one. However, probable interactions of substitution groups and/or of the COO- groups of hydrolysed CPTs with the CAS surface introduce some particularities in the adsorption patterns. As a result, SERS spectra are highly sensitive to hydrolysis and substitutions at distant rings of CPT and uniquely characteristic of each of the CPT derivatives. The pronounced hydrolysis-induced changes, similar in the Raman and SERS spectra of CPTs, involve similar vibrations in the spectra of different CPTs. Vibrational assignments, proposed for the main Raman and SERS bands of CPT and its derivatives (21-lactam-S-CPT, 10,11-(methylenedioxy)-CPT, CPT-11, SN-38 and topotecan) indicate that most of the bands which decreased upon lactone hydrolysis are those preferentially related to stretching modes of the quinoline rings A and B, and the bands which increased are those of the ring D stretching modes. Our data make the spectroscopic approach very promising for the further investigations of the molecular mechanisms of biological activity of CPTs.
采用拉曼光谱、傅里叶变换拉曼光谱（FT - 拉曼光谱）和表面增强拉曼散射（SERS）光谱对强效抗肿瘤药物喜树碱（CPT）的内酯和羧酸盐形式进行了研究。CPT的拉曼光谱与近红外区域相应的FT - 拉曼光谱具有相似性，这使得可以将后者与其SERS光谱进行比较，以便分析药物与银胶体的相互作用。评估了不同类型的银胶体（用硼氢化钠或柠檬酸钠还原，有无阴离子活化）。已发现用氯离子活化的柠檬酸盐还原胶体（CAS）是对两种形式的CPT进行SERS研究的最佳折衷方案。我们认为，一般来说，CPT通过环B中的氮吸附在CAS上，并且更倾向于平面取向而非垂直取向。然而，水解CPT的取代基团和/或COO - 基团与CAS表面可能的相互作用在吸附模式中引入了一些特殊性。结果，SERS光谱对CPT远端环上的水解和取代非常敏感，并且是每个CPT衍生物的独特特征。CPT的拉曼光谱和SERS光谱中明显的水解诱导变化涉及不同CPT光谱中的相似振动。对CPT及其衍生物（21 - 内酰胺 - S - CPT、10,11 - （亚甲基二氧基） - CPT、CPT - 11、SN - 38和拓扑替康）的主要拉曼和SERS谱带进行的振动归属表明，内酯水解时降低的大多数谱带优先与喹啉环A和B的伸缩模式相关，而增加的谱带是环D伸缩模式的谱带。我们的数据使得光谱方法对于进一步研究CPT生物活性的分子机制非常有前景。
