Nonmetallic carbon monoxide releasing molecules (CORMs)

Abstract

Carbon monoxide (CO) is a gasotransmitter that plays important roles in regulating cell functions and has shown therapeutic effects in clinic studies. CO releasing molecules (CORMs), which allow controlled release of CO in physiological conditions, have been intensively studied in the past decade. While most CORMs are metal complexes, several nonmetallic CORMs have also been developed and most of them were reported in recent years. The major advantages of nonmetallic CORMs are potentially low toxicity and easy modification for property tuning. Syntheses, CO-release mechanisms, biological behaviors, and physicochemical properties of these nonmetallic CORMs are reviewed here. The first part of this short review covers the nonmetallic CORMs that do not require irradiation to release CO, which includes methylene chloride, CORM-A1 and its derivatives, amine carboxyboranes, and bimolecular CORMs. The second part focuses on the CORMs that release CO under irradiation (PhotoCORMs) including unsaturated cyclic diketones, xanthene carboxylic acids, meso-carboxy BODIPYs, and hydroxyflavones. Future prospects are discussed at the end of this review.

Metal-free carbon monoxide-releasing micelles undergo tandem photochemical reactions for cutaneous wound healing

“…Although metal carbonyls hold great promise in both laboratory and clinical investigations, 9,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] the development of metal-free CORMs has recently been receiveing increasing attention. 27 In this context, boranocarbonates, 28 CO-releasing prodrugs operated in a "click and release" manner, [29][30][31] and photoresponsive organic CORMs such as 3-hydroxyavone (3-HF) derivatives, [32][33][34][35][36][37] xanthene-9-carboxylic acid, 38 BODIPY derivatives, 39 and aromatic a-diketone derivatives 40 have been developed.…”

Design and Synthesis of New Protease‐Triggered CO‐Releasing Peptide–Metal‐Complex Conjugates

“…However, a person would need to inhale a comparably high concentration of the gas to attain a meaningful concentration in the body. [5c] This hampers the clinical use of carbon monoxide gas because of the risk of intoxication. [5c] Therefore, the use of CO as a therapeutic agent requires the development of alternative methods for its delivery.…”

“…[5c] This hampers the clinical use of carbon monoxide gas because of the risk of intoxication. [5c] Therefore, the use of CO as a therapeutic agent requires the development of alternative methods for its delivery. Carbon monoxide releasing molecules (CORMs) are compounds capable to of delivering controlled amounts of CO to the body without affecting the level of COHb produced.…”

Acetoxymethyl Concept for Intracellular Administration of Carbon Monoxide with Mn(CO)3‐Based PhotoCORMs

“…[7][8][9][10][11] The therapeutic administration of gaseousC Oi squite challenging due to its toxicity.T herefore diverse concepts have been developedt os afely administer this signaling molecule with carbon monoxide releasing molecules (CORMs). [12] Several preconditions must be fulfilled by thesec ompoundss uch as non-toxicity of the CORMs as well as of their degradation products after CO liberation, triggered CO release at ap redeterminedt ime at the disease site, and also releasek inetics betweenm inutesa nd an hour.E vent houghn on-metallic CORMs are known and gaining interesti nr ecent years, [13] the majority of CORMs are based on metal carbonyl complexesw ith the focus on essential metals. [14][15][16] Despite the fact that diverse CO releaset riggersh ave given satisfactory results, the light-triggered liberation of carbon monoxide from metalc arbonyl complexes (photoCORMs) [16] seems to be advantageous due to often negligible interference with biological tissues and ac omplete dissociation of all carbonyl ligands.…”