This work reports the reduction of sulfoxides with boranes, in excellent yields, catalyzed by oxo-rhenium complexes (1 mol %) at room temperature under air atmosphere. The best results were obtained ...with catecholborane (HBcat) in the catalytic systems HBcat/ReIO2(PPh3)2, HBcat/Re2O7, and HBcat/MTO. DFT calculations were performed for the system based on ReIO2(PPh3)2, which was studied in more detail. The reaction starts with the formation of ReIO2(R2SO)2, followed by addition of the first molecule of HBcat and loss of R2S. In a second step, a second HBcat molecule attacks the Re(VII) intermediate, reducing the metal back to Re(V), while H2 and catBOBcat are released and the Re catalyst is regenerated, reentering the reaction cycle. The computed reaction barriers are much lower than those for any alternative pathway that could be envisaged.
The MoIV complex (η5-indenyl)(η5-cyclopentadienyl)Mo(MeCN)2(BF4)2 (1) has been used to promote two acid-catalyzed epoxide ring-opening reactions under ambient conditions. The alcoholysis of ...styrene oxide in neat ethanol gave 2-ethoxy-2-phenylethanol in quantitative yield within 10 min. The use of an ionic liquid (IL) as a cosolvent benefitted catalyst solubility and recycling while not impairing catalytic performance. Complex 1 in 1,2-dichloroethane was effective for the isomerization of α-pinene oxide to campholenic aldehyde (CPA), leading to 87% yield at 1 h of reaction. The same yield could be achieved within 1 min by using the IL CholineNTf2 as a solvent. CPA yields at 1 min reached near-quantitative values (98%) upon recycling of the catalyst/IL mixture, demonstrating an unparalleled combination of activity, selectivity and recyclability for this commercially important reaction. Considering the catalytic features of the 1/IL system, a CPA process flow diagram is proposed and compared to patented technology.
This work reports the use of MoO2Cl2 as a novel catalyst for C−P bond formation, exemplified here by the hydrophosphonylation of aldehydes. A series of α-hydroxyphosphonates was prepared in excellent ...yields using the catalytic system HP(O)(OEt)2/MoO2Cl2 (5 mol %) under solvent-free conditions or at refluxing THF. DFT calculations indicate that the PO bond coordinates to molybdenum while the P−H hydrogen is transferred to one MoO oxygen atom. The active species then reacts with the aldehyde to form the α-hydroxyphosphonates. The calculated activation barriers (free energies) are ca. 20 kcal mol−1.
We have designed and synthesised a Ru(CO)3Cl2(NAC) pro‐drug that features an N‐acetyl cysteine (NAC) ligand. This NAC carbon monoxide releasing molecule (CORM) conjugate is able to simultaneously ...release biologically active CO and to ablate the concurrent formation of reactive oxygen species (ROS). Complexes of the general formulae Ru(CO)3(L)32+, including Ru(CO)3Cl(glycinate) (CORM‐3), have been shown to produce ROS through a water–gas shift reaction, which contributes significantly, for example, to their antibacterial activity. In contrast, NAC‐CORM conjugates do not produce ROS or possess antibacterial activity. In addition, we demonstrate the synergistic effect of CO and NAC both for the inhibition of nitric oxide (formation) and in the expression of tumour‐necrosis factor (TNF)‐α. This work highlights the advantages of combining a CO‐releasing scaffold with the anti‐oxidant and anti‐inflammatory drug NAC in a unique pro‐drug.
Pro and anti—pro‐drug/anti‐inflammatory! An N‐acetyl cysteine carbon monoxide releasing molecule (NAC‐CORM; see figure) complex conjugate was designed to simultaneouly release CO and the anti‐oxidant and anti‐inflammatory drug NAC. NAC‐CORM is able to release CO in aqueous solution and live cells while the ligand NAC abolishes reactive oxygen species (ROS) produced during CO release. In addition, CO and NAC delivered as a unique pro‐drug act synergistically resulting in an enhanced anti‐inflammatory response, as demonstrated by both the inhibition of nitrite production and in the expression of tumour‐necrosis factor‐α.
•β-cyclodextrin (CD) and Et4NMo(CO)5Br (1) were coground in a planetary ball mill.•The CD component in the 1-βCD solid dispersion improves the aqueous solubility of 1.•Hydrolysis-induced CO release ...from 1 and 1-βCD was compared via the myoglobin assay.•βCD increases the half-life of CO release from 1, while decreasing the efficiency.•The bactericidal activity of 1 against E. coli cells was retained in the 1-βCD product.
In the present work the possibility of improving the solubility, bioavailability and bactericidal activity of the carbon monoxide releasing molecule (CORM) Mo(CO)5Br− (as its tetraethylammonium salt) (1) by solvent-free co-grinding with β-cyclodextrin (βCD) in a planetary ball mill was investigated. Data obtained by FT-IR spectroscopy, Raman spectroscopy, powder X-ray diffraction and thermogravimetric analysis showed that, other than a small decrease in the crystallinity of 1, the co-grinding process produced a finely dispersed physical mixture of crystalline CORM and crystalline excipient. The aqueous solubility of 1 in the 1-βCD product was enhanced with respect to sparingly soluble pure 1, which might be ascribed to increased wettability and a CD-CORM interaction in solution. Investigation of the CO release kinetics by the standard myoglobin assay showed that the half-life of CO release increased from ca. 6 min for 1 to ca. 19 min for 1-βCD, while the number of equivalents released decreased from 3.2 to 1.8. The antibacterial properties of 1 and 1-βCD were evaluated using the broth microdilution method to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against the model Gram-negative bacterium, Escherichia coli. The compounds showed similar growth inhibitory (MIC values of 200 μM) and bactericidal (MBC/MIC ≈ 2) effects. Bacterial viability assays corroborated the MBC/MIC studies, showing 3 logs (99.9% of relative light units - RLU) reduction in viable cell count after 15 min exposure to 2 × MIC. Although the CORM-CD system displays a lengthening of the half-life of CO release and a decrease in the CO release efficiency relative to 1, the co-grinding with βCD does not affect the bactericidal activity of the CORM. Overall, the βCD could be a suitable excipient for the development of immediate-release formulations of CORMs like the pentacarbonyl complex 1.
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OBJECTIVE—Carbon monoxide (CO) is a weak soluble guanylyl cyclase stimulator, leading to transient increases in cGMP and vasodilation. The aim of the present work was to measure the effect of ...CO-releasing molecules (CORMs) on the cGMP/nitric oxide (NO) pathway and to evaluate how selected CORMs affect NO-induced vasorelaxation.
METHODS AND RESULTS—Incubation of smooth muscle cells with some but not all of the CORMs caused a minor increase in cGMP levels. Concentration-response curves were bell-shaped, with higher CORMs concentrations producing lower increases in cGMP levels. Although exposure of cells to CORM-2 enhanced cGMP formation, we observed that the compound inhibited NO-stimulated cGMP accumulation in cells and NO-stimulated soluble guanylyl cyclase activity that could be reversed by superoxide anion scavengers. Reactive oxygen species generation from CORMs was confirmed using luminol-induced chemiluminescence and electron spin resonance. Furthermore, we observed that NO is scavenged by CORM-2. When used alone CORM-2 relaxed vessels through a cGMP-mediated pathway but attenuated NO donor-stimulated vasorelaxation.
CONCLUSION—We conclude that the CORMs examined have context-dependent effects on vessel tone, as they can directly dilate blood vessels, but also block NO-induced vasorelaxation.
MoCl2O2 catalyzes the hydrosilylation reaction of aldehydes and ketones, as well as the reduction of other related groups, in apparent contrast to its known behavior as an oxidation catalyst. In this ...work, the mechanism of this reaction is studied by means of density functional theory calculations using the B3LYP functional complemented by experimental data. We found that the most favorable pathway to the first step, the SiH activation, is a 2+2 addition to the MoO bond, in agreement with previous and related work. The stable intermediate that results is a distorted‐square‐pyramidal hydride complex. In the following step, the aldehyde approaches this species and coordinates weakly through the oxygen atom. Two alternative pathways can be envisaged: the classical reduction, in which a hydrogen atom migrates to the carbon atom to form an alkoxide, which then proceeds to generate the final silyl ether, or a concerted mechanism involving migration of a hydrogen atom to a carbon atom and of a silyl group to an oxygen atom to generate the silyl ether weakly bound to the molybdenum atom. In this MoVI system, the gas‐phase free energies of activation for both approaches are very similar, but if solvent effects are taken into account and HSiMe3 is used as a source of silicon, the classical mechanism is favored. Several unexpected results led us to search for still another route, namely a radical path. The energy involved in this and the classical pathway are similar, which suggests that hydrosilylation of aldehydes and ketones catalyzed by MoCl2O2 in acetonitrile may follow a radical pathway, in agreement with experimental results.
Insertion, migration, or radical? The mechanism of the hydrosilylation reaction of aldehydes and ketones catalyzed by MoCl2O2 has been studied by means of density functional theory calculations and complemented by experimental data. The graphic shows possible intermediates.
This work reports a novel method for the deoxygenation of aromatic and aliphatic sulfoxides catalyzed by oxo-rhenium complexes without adding any reducing agent. The oxo-rhenium complex ReOCl3(PPh3)2 ...proved to be very efficient for the deoxygenation of several sulfoxides with tolerance of different functional groups.
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