Fluorescent cyclodextrin carriers for a water soluble Zn^II pyrazinoporphyrazine octacation with photosensitizer potential

Abstract

A nitro-benzofurazan-triazolyl carboxymethylated beta-cyclodextrin (NBFT-CM beta CyD) and an oligomer of carboxymethyl beta-cyclodextrin (sodium salt), crosslinked with epichlorohydrin and labeled with rhodaminyl groups (p beta CyD-Rh), exhibit very high affinity in aqueous solution for octacationic photosensitizer [(CH3)(8)LZn](8+) neutralized by I- ions (L = tetrakis-2,3-[5,6-di(2-(pyridiniumyl) pyrazino] porphyrazinato dianion). The photosensitizer (PS) forms complexes with 1 : 2 and 2 : 2 CyD: PS stoichiometry, which were characterized as binding constants and UV-Vis absorption and fluorescence properties. The self-association tendency of [(CH3)(8)LZn](8+), leading to a monomer-dimer equilibrium shift towards the dimer even at very low concentrations (approximate to 10 (6) M), is not contrasted by either NBFT-CM beta CyD or the p beta CyD-Rh oligomer, both of which completely convert the [(CH3)(8)LZn](8+) monomer fraction to the dimer form in the bound state. Quenching of fluorescence observed in [(CH3)(8)LZn](8+) upon binding with either hosts is consistent with the conversion of the monomer to the negligibly fluorescent dimer. The complexes formed with the CM beta CyD units of the p beta CyD-Rh oligomer have average association constants, which are larger by 6-7 orders of magnitude than those with the CM beta CyD monomer in the NBFT-labeled derivative

Effect of cyclodextrin complexation on solubility of novel anti-Alzheimer 1,2,4-thiadiazole derivative

“…Phase solubility study It is well known that solubility of lipophilic compounds can be enhanced by adding CDs to the solution [5][6][7][8]. In this connection, the solubilizing capacity of CDs toward I was studied by phase solubility method [13].…”

“…On the contrary, the polar exterior of CD allows the complex to interact favorably with water and this process determines the solubility rise. It has been demonstrated that complex formation with CDs can considerably increase the solubility of numerous drugs [4][5][6]. Moreover, the solid dosage forms prepared on the basis of CD inclusion complexes and designed for an oral administration displayed the increased dissolution rate [7,8].…”

“…In most cases, new drug candidates are poorly soluble in water. However, this property could be improved by several methods, among which there are particle size reduction by different techniques (e.g., milling, homogenization) [1], co-crystals technologies [2], use of different excipients (e.g., water-soluble biopolymers) [1], incorporation of an active ingredient into micelles, liposomes and nanoparticles [3] as well as complexation with cyclodextrins [4][5][6][7][8].…”