Encapsulation of 3-hydroxyflavone and fisetin in b-cyclodextrins: Excited state proton transfer fluorescence and molecular mechanics studies q Anwesha Banerjee, Pradeep K. Sengupta * Biophysics Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata 700064, West Bengal, India Received 11 April 2006; in final form 26 April 2006 Available online 5 May 2006 Abstract Excited-state intramolecular proton-transfer (ESIPT) and dual emission properties (emission profile, anisotropy and decay kinet- ics) of 3-hydroxyflavone (a synthetic, model flavonol) and fisetin (3,7,3 0 ,4 0 -OH-flavone, a therapeutically active plant flavonol) have been exploited to study their encapsulation in nano-cavities comprising of natural and chemically modified b-cyclodextrins. In the presence of b-CDs, both the flavonols show significantly enhanced relative yields (along with changes in other emission parameters) of the tautomer emission. In addition, for fisetin, large blue shifts are observed for the normal emission (which has significant charge transfer character). From these we infer that the flavonols are encaged in predominantly hydrophobic micro-environments, where external hydrogen bonding perturbations (interfering with the intrinsic ESIPT), and dipolar relaxation effects, are minimized. This is further explained from results of molecular mechanics calculations which indicate selectivity in orientation of the encapsu- lated flavonols. Moreover, chemical modification of the b-CDs is found to profoundly influence the binding affinities of the guest flavonols. Ó 2006 Elsevier B.V. All rights reserved. 1. Introduction In 1936 Rusznyak and Szent-Gyo ¨ rgii first recognized the therapeutically beneficial role of dietary flavonoids [1], which are polyphenolic compounds abundant in common plant based food and beverages (e.g. citrus fruits, apple, soy products, onion, broccoli, tea and red wine). The last decade has witnessed a remarkable renascence of interest in this area, marked by an explosive growth of research on various bioactive flavonoids, which have proved to be effective against a wide range of free radical mediated and other human diseases [2,3] (e.g. atherosclerosis, ische- mia, neuronal degeneration, cancers, tumors, allergies, car- diac problems, inflammation, AIDS, etc.). The high potency and low systemic toxicity of these compounds make them viable alternatives to conventional therapeutic drugs. However, since such applications are often limited by poor water solubility, there is much current interest in using suitable drug delivery vehicles (e.g. cyclodextrins) capable of ensuring increased hydrosolubility, and conse- quently improved bioavailability of these drugs. On a different scenario, a major class of natural flavo- noids of widespread occurrence, namely flavonols (3- hydroxyflavones) have emerged as one of the best known molecular systems exhibiting excited state intramolecular proton transfer (ESIPT) and dual fluorescence behavior [4–6]. Consequently, there is enormous interest on such compounds as prototypes for mechanistic studies of 0009-2614/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.cplett.2006.05.006 q This research was presented at the National Symposium on ‘Mole- cules, Interactions and Design: A Biophysical Perspective (IBS 2006)’, held under the aegis of the Indian Biophysical Society Kolkata, India, January 7–9, 2006, for which the younger author (A.B.) was recipient of the N.N. Saha Memorial award for best Poster presentation. * Corresponding author. Fax: +91 33 23374637. E-mail addresses: pradeepk.sengupta@saha.ac.in, pradeepsinp@ yahoo.co.in (P.K. Sengupta). www.elsevier.com/locate/cplett Chemical Physics Letters 424 (2006) 379–386