Visible light-activatable cyclodextrin-conjugates for the efficient delivery of nitric oxide with fluorescent reporter and their inclusion complexes with betaxolol
Abstract
This contribution reports the design, synthesis, photochem. properties and drug inclusion capability of two novel β-cyclodextrin (βCD) conjugates, βCD-NBFNO1 and βCD-NBFNO2, covalently integrating an N-nitroso amino-nitro-benzofurazan in the primary and secondary hydroxyl rims of the βCD scaffold, resp. through flexible spacers of different length. Both βCD conjugates are water-sol. and release nitric oxide (NO) under the input of either blue or green light, with quantum yields ΦNO (blue) = 0.13, 0.31 and ΦNO (green) = 0.007, 0.013 resp., the former representing the largest values ever reported for nonmetal-contg.
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 amt. of NO generated, without the addn. of external fluorescent agents.
Despite the presence of the appendages, these βCD derivs. are also able to complex betaxolol, a β-blocker drug widely used for the redn. of the intraocular pressure, with binding consts. K(b) = 500 +- 50 and 1100 +- 100 M(-1), resp., without affecting the photochem. performances.
In view of the well-known vasodilator properties of NO, the present βCD derivs. represent intriguing candidates for biopharmaceutical research studies addressed to combined therapeutic ocular applications.