CORM-EDE1: A Highly Water-Soluble and Nontoxic Manganese-Based photoCORM with a Biogenic Ligand Sphere

Abstract

[Mn(CO)5Br] reacts with cysteamine and 4-amino-thiophenyl with a ratio of 2:3 in refluxing tetrahydrofuran to the complexes of the type [{(OC)3Mn}2(μ-SCH2CH2NH3)3]Br2 (1, CORM-EDE1) and [{(OC)3Mn}2(μ-SC6H4-4-NH3)3]Br2 (2, CORM-EDE2). Compound 2 precipitates during refluxing of the tetrahydrofuran solution as a yellow solid whereas 1 forms a red oil that slowly solidifies. Recrystallization of 2 from water yields the HBr-free complex [{(OC)3Mn}2(μ-S-C6H4-4-NH2)2(μ-SC6H4-4-NH3)] (3). The n-propylthiolate ligand (which is isoelectronic to the bridging thiolate of 1) leads to the formation of the di- and tetranuclear complexes [(OC)4Mn(μ-S-nPr)2]2 and [(OC)3Mn(μ-S-nPr)]4. CORM-EDE1 possesses ideal properties to administer carbon monoxide to biological and medicinal tissues upon irradiation (photoCORM). Isolated crystalline CORM-EDE1 can be handled at ambient and aerobic conditions. This complex is nontoxic, highly soluble in water, and indefinitely stable therein in the absence of air and phosphate buffer. CORM-EDE1 is stable as frozen stock in aqueous solution without any limitations, and these stock solutions maintain their CO release properties. The reducing dithionite does not interact with CORM-EDE1, and therefore, the myoglobin assay represents a valuable tool to study the release kinetics of this photoCORM. After CO liberation, the formation of MnHPO4 in aqueous buffer solution can be verified.

Manganese(I)-Based CORMs with 5-Substituted 3-(2-Pyridyl)Pyrazole Ligands

“…2.3). As observed in earlier studies [28,[34][35][36], the CO liberation is accompanied by oxidation processes and the formation of paramagnetic manganese(II) complexes. The formation of open shell systems impeded an NMR spectroscopic monitoring of the degradation reaction.…”

“…As observed earlier, degradation of manganese(I)-based photoCORMs upon illumination is accompanied by redox processes [28,[34][35][36], yielding carbonyl-free manganese(II) and manganese(III) complexes or even manganese oxide species. Due to degradation in methanol in an inert atmosphere, methoxides and pyrazolates are observed.…”

“…During CO liberation, most commonly an oxidation to manganese(II) has been observed. In buffered aqueous solutions, manganese(II) hydrogenphosphate MnHPO4 of low toxicity has been identified after CO release from dinuclear [{(OC)3Mn}2(µ-SC2H4NH3)3]Br2 (CORM-EDE1 [28]). …”

Synthesis and Characterization of Manganese(I) Carbonyl Complexes of the Type [(OC)4Mn{μ‐P(R)Aryl}]2

“…[1] The preferred synthetic route to these thiolate complexes involves the metalation of thiols with Mn 2 (CO) 10 , commonly yielding mixtures of dinuclear and tetranuclear complexes of the types [(OC) 4 Mn(μ-SR)] 2 and [(OC) 3 Mn(μ 3 -SR)] 4 with bridging thiolato ligands. Alternatively, the metathetical approach via the reaction of [(OC) 5 MnBr] with KSR also proofed to offer a suitable access to these complexes.…”

“…In contrast to the common di-and tetranuclear molecular structures, the 2,4,6-trimethylphenyltiolato manganese(I) complex precipitated as the trinuclear complex [(OC) 4 Mn(μ-SMes)] 3 (Mes = C 6 H 2 -2,4,6-Me 3 , mesityl) with a six-membered Mn 3 S 3 ring. [1] In complexes with carbonyl ligands trans-arranged to each other, a weakening of the Mn-CO bond has been observed by IR spectroscopy and X-ray structure determination. Consequently, the tetranuclear heterocubane-type complexes form due to the fact that a free electron pair at sulfur competes with such a carbonyl ligand; liberation of CO and related ligand exchange then converts dinuclear [(OC) 4 Mn(μ-SR)] 2 into tetranuclear [(OC) 3 Mn(μ 3 -SR)] 4 .…”