Visible light-activatable cyclodextrin-conjugates for the efficient delivery of nitric oxide with fluorescent reporter and their inclusion complexes with betaxolol

This contribution reports the design, synthesis, photochemical properties and drug inclusion capability of two novel beta-cyclodextrin (beta CD) conjugates, beta CD-NBFNO1 and beta CD-NBFNO2, covalently integrating an N-nitroso amino-nitro-benzofurazan in the primary and secondary hydroxyl rims of the beta CD scaffold, respectively through flexible spacers of different length. Both beta CD conjugates are water-soluble and release nitric oxide (NO) under the input of either blue or green light, with quantum yields Phi(NO) (blue) = 0.13, 0.31 and Phi(NO) (green) = 0.007, 0.013 respectively, the former representing the largest values ever reported for nonmetal-containing NO donors activatable by visible light. The good contrast between the fluorescence green emission of the chromogenic moiety after and before the NO release permits the easy and in real-time quantification of the amount of NO generated, without the addition of external fluorescent agents. Despite the presence of the appendages, these beta CD derivatives are also able to complex betaxolol, a beta-blocker drug widely used for the reduction of the intraocular pressure, with binding constants K-b = 500 +/- 50 and 1100 +/- 100 M-1, respectively, without affecting the photochemical performances. In view of the well-known vasodilator properties of NO, the present beta CD derivatives represent intriguing candidates for biopharmaceutical research studies addressed to combined therapeutic ocular applications.