Elucidation of the CO‐Release Kinetics of CORM‐A1 by Means of Vibrational Spectroscopy

Abstract

CO-releasing molecules (CORMs) are developed for investigations of the interaction between the signaling molecule carbon monoxide (CO) and cells or tissue. Prior to their application these molecules must be fully characterized with respect to their CO-release mechanism. One widely used CORM for biological application is sodium boranocarbonate (CORM-A1), which shows pH-dependent CO liberation. The complete reaction mechanism of CORM-A1 is not fully understood yet. Therefore, in this contribution time-resolved gas-phase IR spectroscopy is used to monitor the headspace above decaying CORM-A1 solutions at four different pH values (5.8 to 7.4). Borane carbonyl is found as an intermediate in the gas phase, which is formed during CORM degradation and further decays to CO. Concentration profiles of a pseudoconsecutive first-order reaction are successfully fitted to specific band areas of the measured gas-phase spectra, and the rate constants are obtained. The production of borane carbonyl is strongly pH dependent (half-lives between 5 and 106 min), whereas the decay of borane carbonyl in the gas phase is nearly constant with a half-life of about 33 min. The ratio of liberated CO molecules per CORM-A1 is determined to be 0.91±0.09, and boric acid is identified as further end product.

Carbon monoxide: An emerging therapy for acute kidney injury

“…196 On the other hand, CO release from both CORM-2 and CORM-3 has been reported to be highly dependent on the presence of thio-species in the media; 197 therefore, CO dose might be difficult to control for in-vivo applications. 198 Later, the same group reported water-soluble CORM-A1 based on boranocarbonate decomposition chemistry. Unlike CORM-1~3, CORM-A1 releases CO in aqueous solution with a half-life of 21 min at pH 7.4 and the release can be stimulated at a lower pH with a shorter half-life.…”

“…199 At the same time, it forms borane as a reductive intermediate, which undergoes reaction with water to generate one molecule of boric acid and hydrogen as the formal byproducts. 198 Although CORM-A1 does not contain a transition metal, boron as an ultra-trace element has been termed as "metalloid". Therefore, CORM-A1 is included in this category for discussion purposes.…”

Carbon monoxide formation from trimethylamine-boranecarboxylate: DFT studies of SNi and chelotropic mechanisms

“…CO has been identied as a hydrolysis product of TMA-BH 2 COOH 7 and other CORMs. 29 The goal of this study is to rationalize the relatively facile hydrolysis and decarbonylation reactions of TMA-BH 2 -COOH, as well as assess the role of solvent water on reactivity.…”

CO-Releasing Materials: An Emphasis on Therapeutic Implications, as Release and Subsequent Cytotoxicity Are the Part of Therapy

“…Along with organometallic complexes, the miscellaneous compounds can be nominated as the CORMs family. In this scenario, numerous nonmetallic compounds [85] have been accomplished by entertaining the CO release such as silica-carboxylates [86], borano-carbonates [87], borano-carbamates [88], xanthene carboxylic acid (XCA) [89], unsaturated cyclic diketones (DKs) [90], methylene chloride (MC) [91,92], meso-carboxy BODIPYs [46], hydroxy-flavones [93] (Scheme 2). Furthermore, 1,2-disubstituted ferrocenes belongs to an aldehyde family, unfavorably elicits the toxicity and its slow release mechanism restricts the researchers from developing another nonmetallic CORMs (NCORMs).…”