ARTICLE pubs.acs.org/JPCC
Modulation of Small Molecule Induced Architecture of Cyclodextrin Aggregation by Guest Structure and Host Size Prasun Ghosh, Arnab Maity, Tarasankar Das, Jyotirmayee Dash,* and Pradipta Purkayastha* Department of Chemical Sciences, Indian Institute of Science Education and Research, Kolkata, Mohanpur Campus, Mohanpur 741252, WB, India
bS Supporting Information ABSTRACT: A small molecule based on bisphenylethynyl amide meta linked to 2,6-pyridine can induce cyclodextrin (CD) aggregation through a possible 1:3 guest host motif. Most of the small molecules induce CD nanotubular bundles principally through 1:2 guest host unit capsules and aggregate through hydrogen bonding among the hydroxyl groups present on the rims of the CD molecules. The N,N-dimethyl aminopropyl carboxamide side chain and the central pyridine ring of 6-bromo-2-phenylethylaminopyridine (BPEAP) induces nanotubular bundles with α-CD and laminar bundles with β- and γ-CDs, which, as a consequence, may result in formation of pores in the aggregates that can find wide applications in biological storage machinery. The stoichiometry of the ingredients of the unit capsules has been evidenced by Job’s plot. The size-dependent suprastructures induced by BPEAP have been studied by steady state and time-resolved fluorescence spectroscopy and atomic force microscopy.
’ INTRODUCTION Self-aggregation of cyclodextrins (CDs) in water is an aspect that is still not completely understood. A number of reports have been published on this aspect using the concept of self-aggregation of CD with or without the aid of an externally added compound.1 5 In general, native CDs can form aggregates in water with the size of about 200 300 nm, which considerably depends on the type of CDs.6 8 According to Loftsson et al., the aggregates, having noninclusion complexation or micelle-like structures, were able to solubilize lipophilic drugs.9 At low pH ionization of the hydroxyl groups leads to dispersion of these aggregates, leading in turn to increased solubility. It has also been noticed that solubility of β-CD is increased in the presence of structure breaking solutes but with retention of aggregates.1 The driving force for the self-assembly of cyclodextrin molecules can thus be considerably ascribed to hydrogen bonding.7,10 The CDs prefer to line up in ideally parallel or staggered parallel arrangement with quadrupolar character.10 The six-, seven-, and eight-membered sugar residues constituting α-, β-, and γ-CDs have been the focus of interest to researchers in pure and applied fields.11,12 The hydrophobic inner cavities of the truncated conelike structures of the CDs have 4 8 Å diameters. Depending on the relative sizes of the CDs and the guest molecules, more than one guest can be accommodated inside a single CD cavity.13 Formation of small molecule induced CD nanotubes or nanorods has been the topic of interest for many groups in applied fields of chemical research.2 4,14,15 Our recent observations have proved that r 2011 American Chemical Society
formation of small molecule induced CD nanotubular suprastructures depends significantly on the concentration of the guest.4,17,18 We have shown spectroscopically that the CD nanotubular aggregation takes place through primary and secondary interactions via hydrogen bonding.18 The present report describes the importance of the structure of guest molecule as well as the host on building up of the CD suprastructures. The molecule that we have opted as the guest system is a bis-phenylethynyl amide meta-linked to 2,6-pyridine (I), as shown in Scheme 1, is a potent G-quadruplex DNA binding small molecule.19,20 We have studied the impact of molecular structure on CD aggregation motif. We observed that even the smallest cavity sized α-CD can form well developed nanotubular suprastructures depending on the concentration of the guest compound through the basic 1:2 guest host encapsulation mode.4,18 Because of restriction in the internal cavity size, α-CD leads to typically patterned guest binding. This is different from the binding motif of β- and/or γ-CDs.4,17,21 From the structural features of 6-bromo-2-phenylethylaminopyridine (BPEAP) (I) (Scheme 1) it is apparent that the hydrophobic amine portions can get encapsulated inside the hydrophobic CD cavities. The central pyridine ring also offers another possible site for encapsulation with the hydrophobic CD cavities. Thus, it can be hypothesized that the initial encapsulation of the amine Received: July 4, 2011 Revised: August 24, 2011 Published: September 26, 2011 20970
dx.doi.org/10.1021/jp206299y | J. Phys. Chem. C 2011, 115, 20970–20977
The Journal of Physical Chemistry C
ARTICLE
Scheme 1. Equilibrium between the Neutral Form of BPEAP (I) and Its Ionic Counterpart (II)
portions by two CD host molecules will control the approach of the third CD to encapsulate the pyridinyl moiety. Herein we have investigated this hypothesis by employing fluorescence spectroscopy and atomic force microscopy (AFM) and proposed a structural schematic for the BPEAP-induced CD suprastructure formation.
’ EXPERIMENTAL SECTION Materials. BPEAP was prepared and purified by using literature procedure.19 Stock solution of the compound (1.001 10 3 M) was prepared in triple distilled water. The final concentration under different conditions of BPEAP was 2 10 6 M. Cyclodextrins were bought from Sigma-Aldrich, WI, USA and used as received. Methods. The absorption spectra were recorded using a Varian Cary 300 Bio UV vis spectrophotometer. Fluorescence measurements were performed using a PerkinElmer LS 55 scanning spectrofluorimeter. The fluorescence lifetimes were measured by the method of time-correlated single-photon counting using a picosecond spectrofluorimeter from Horiba Jobin Yvon IBH. The instrument was equipped with FluoroHub single photon counting controller, Fluoro3PS precision photomultiplier power supply and FC-MCP-50SC MCP-PMT detection unit. A laser head or a nano-LED pulsed diode powered by a pulsed diode controller (IBH) was used as the excitation light source. The excitation wavelength was 281 nm. The typical response time of this laser head was
