The deoxy-myoglobin (deoxy-Mb)/carbonmonoxy-myoglobin (Mb-CO) UV-vis assay is the principal method used for quantifying the rates of CO release from CO-releasing molecules (CO-RMs) that might possess therapeutic benefits. Some issues emerge when the Mb-CO assay is utilized for testing CO-RMs with novel structures, which are comprehensively discussed here for the first time. Two methods for processing raw UV-vis spectroscopic data generated from the assay are presented in this paper.
The CO-releasing ability of a diverse library of primary metal carbonyl complexes has been assessed using a deoxymyoglobin-carbonmonoxymyglobin assay. A wide spectrum of rates for the CO-release process was observed in aqueous systems. For octahedral d(6) complexes, the rate was found to decrease in the sequence FeI(2)(CO)(4) > [NEt(4)][V(CO)(6)] > MnBr(CO)(5) > Cr(CO)(6) implying that CO-release is not controlled by the metal-carbon bond strengths. Within the series, [NEt(4)][MX(CO)(5)] (M = Cr, Mo, W; X =Cl, Br, I), the rate of CO-release was found to decrease down the group (Cr > Mo > W), whilst within the chromium series a similar trend was observed for the halide (Cl > Br > I). The d(4) complexes [NEt(4)][MI(3)(CO)(4)] (M = Mo, W) exhibit faster release than their d(6) congeners. A mechanistic investigation into the [NEt(4)][MX(CO)(5)] series revealed the intermediacy of [[M(CO)(5)](2)(mu-X)](-) in the CO-release process and that the hydrolysis of the M-X bond, rather than the intrinsic strength of M-CO bonds, controls the rate of CO-release in aqueous systems.
The first carbon monoxide-releasing molecules (CO-RMs) based on mu2-alkyne dicobalt(0)hexacarbonyl complexes are reported. The alkyne substituents significantly affect the rate of CO-release, cytotoxicity and cell viability. Mechanistic studies provide insight into the CO-RM activation pathways.
An investigation into the CO-releasing properties of
a range of iron tricarbonyl and chromium and molybdenum tetracarbonyl
complexes is presented. Iron tricarbonyl complexes containing the
2,5-bicyclo[2.2.1]heptene (norbornadiene) ligand are shown to be effective
CO-releasing molecules, in which the rate and extent of CO release
may be modulated by modification of the norbornadiene framework. Species
containing the parent norbornadiene and those with a substituent at
the 7-position of the organic ligand exhibit CO release; those containing
ester substituents at the 2- and/or 3-positions do not. A mechanism
for CO release in this species is proposed which involves initial
norbornadiene dissociation, a suggestion which is supported by the
spectroscopic data and the observation that the addition of excess
substituted norbornadiene retards the rate of CO release. CO release
from the diester-containing norbornadiene complex may be promoted
photochemically, and cell viability studies indicate that in the absence
of light this complex is nontoxic, making it an excellent candidate
for further study as a photo-CO-RM. Both the chromium and molybdenum
tetracarbonyl complexes release CO, which in the case of the molybdenum
analogue is rapid.
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