Ž . Biochimica et Biophysica Acta 1334 1997 349–360 Structure–activity relation in camptothecin antitumor drugs: why a detailed molecular characterisation of their lactone and carboxylate forms by Raman and SERS spectroscopies? Igor Chourpa a , Abdel Beljebbar a , Ganesh D. Sockalingum a , Jean-Franc ¸ois Riou b , Michel Manfait a, ) a Laboratoire de Spectroscopie Biomoleculaire, UFR de Pharmacie, UniÕersite de Reims Champagne-Ardenne, 51 rue Cognacq Jay, ´ ´ F-51096 Reims, France b Rhone-Poulenc Rorer, S.A., Departement de Biologie, F-94403 Vitry-sur-Seine, France ˆ ´ Received 7 June 1996; revised 16 September 1996; accepted 14 October 1996 Abstract Ž . Lactone and carboxylate forms of potent antitumor agents, camptothecins CPTs have been studied by Raman, Ž . Ž . 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 Ž . reduced with sodium borohydride or sodium citrate, with or without activation by anions have been evaluated. Ž . 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 andror of the COO y 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 Ž Ž . . 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. Keywords: Raman spectroscopy; Fourier transform Raman spectroscopy; Raman scattering, surface-enhanced; Colloid; Camptothecin; Hydrolysis www Ž . x x x Abbreviations: CPT, camptothecin; CPT-11, 7-ethyl-10- 4- 1-piperidino -1-piperidino carbonyl oxy camptothecin; SN-38, 7-ethyl- wŽ . x 10-hydroxycamptothecin; topotecan, 9- dimethylamino -methyl -10-hydroxycamptothecin; SERS, surface-enhanced Raman scattering; FT-Raman, Fourier-transform Raman; CAS, chloride-activated sol; NAS, non-activated sol. ) Corresponding author. Fax: q33 3 26.05.35.50. 0304-4165r97r$17.00 Copyright q 1997 Published by Elsevier Science B.V. All rights reserved. Ž . PII S0304-4165 96 00113-4