Fluorescein Analogue Xanthene-9-Carboxylic Acid: A Transition-Metal-Free CO Releasing Molecule Activated by Green Light

Abstract

6-Hydroxy-3-oxo-3H-xanthene-9-carboxylic acid is introduced as the first transition-metal-free carbon monoxide releasing molecule activated by visible light (photoCORM). This water-soluble fluorescein analogue releases carbon monoxide in both water and methanol upon irradiation at 500 nm. When selectively irradiated in the presence of hemoglobin (Hb) under physiological conditions, released CO is quantitatively trapped to form carboxyhemoglobin (COHb). The reaction progress can be accurately monitored by characteristic absorption and emission properties of the reactants and products.

Toward Carbon Monoxide–Based Therapeutics: Critical Drug Delivery and Developability Issues

“…This would require the development of “caged” CO for release at the appropriate time and rate. There have been recent efforts in developing metal-based CO-RMs (or CO-prodrugs), 17, 39-42 encapsulated CO-RMs, 43-46 photo-sensitive organic CO-RMs, 47-49 and organic CO-prodrugs that spontaneously release CO under physiological conditions. 50 In addition to normal delivery route challenges, there are some special factors related to CO-based therapeutics, all of which would affect the development of pharmaceutically acceptable forms of a CO-prodrug.…”

“…86-89 Fluorescein analogue 8 (Figure 3) was the first reported transition metal free and water soluble photo-sensitive CO-RM. 47 After irradiation with visible light (λ = 503 ± 15 nm) in phosphate buffer saline (PBS) buffer (pH = 7.4), compound 8 could release CO with a half-life of around 4.5 h. This release rate is much slower compared to most metal based CO-RMs, which tend to have half-lives in the range of minutes. Release of CO was demonstrated by elucidating the chemical structure of the by-product 10 and using a standard hemoglobin binding assay.…”

Photo-Controlled Release of NO and CO with Inorganic and Organometallic Complexes

“…Owing to an interest in using related compounds for photochemical CO 2 reduction Ishitani and coworkers [163] prepared complexes of the type fac-Re(bpy)(CO) 3 (PR 3 ) + , where the phosphine , because of its π-acidity renders the CO trans to it photolabile. Based upon these various observations, Pierri et al [164] were able to prepare a truly multifunctional rhenium complex that displayed a strong …”

Carbon monoxide – physiology, detection and controlled release

“…118,119 The first protonation step yields Na[H 3 B-CO 2 H] and a second leads to split-off of water and formation of H 3 B-CO, which rapidly loses CO. 120 Further, a water-soluble fluorescein analogue 6-hydroxy-3-oxo-3 H -xanthene-9-carboxylic acid was recently introduced as the first transition metal-free CORM activated by light at a wavelength of 500 nm. 121 Organometallic compounds have recently gained significant attention in potential medicinal treatments. 122 Up to now, metal carbonyl complexes represent preferred reagents to deliver CO because they offer manifold advantageous variations, such as nature and oxidation state of the metal centre (size, charge, Pearson hardness, Lewis acidity, structural diversity), number of carbonyl ligands, nature of coligands (charge, Lewis basicity, π-bonding properties, complex stability) and outer coordination sphere (solubility, Brønsted acidity, amphiphilic character, Fig.…”