Carlos C. Romão

CORM-3 Reactivity toward Proteins: The Crystal Structure of a Ru(II) Dicarbonyl-Lysozyme Complex

CORM-3, [fac-Ru(CO)(3)Cl(κ(2)-H(2)NCH(2)CO(2))], is a well-known carbon monoxide releasing molecule (CORM) capable of delivering CO in vivo. Herein we show for the first time that the interactions of CORM-3 with proteins result in the loss of a chloride ion, glycinate, and one CO ligand. The rapid formation of stable adducts between the protein and the remaining cis-Ru(II)(CO)(2) fragments was confirmed by Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES), Liquid-Chromatography Mass Spectrometry (LC-MS), Infrared Spectroscopy (IR), and X-ray crystallography. Three Ru coordination sites are observed in the structure of hen egg white lysozyme crystals soaked with CORM-3. The site with highest Ru occupancy (80%) shows a fac-[(His15)Ru(CO)(2)(H(2)O)(3)] structure.

MCM-41 functionalized with bipyridyl groups and its use as a support for oxomolybdenum(VI) catalysts

The ordered mesoporous silica MCM-41 was covalently grafted with (3-chloropropyl)trimethoxysilane. Chloro substitution by the anion [4-CH2-4′-Me-2,2′-bipyridine]− gave a ligand-silica containing ca. 0.3 mmol bipyridyl groups per gram. Powder X-ray diffraction and nitrogen adsorption–desorption analysis demonstrated that the textural characteristics of the support were preserved during the grafting experiments and that the channels remained accessible, despite sequential reductions in surface area, pore volume and pore size. The coupling reactions were monitored by 29Si MAS NMR and 13C CP MAS NMR spectroscopy. Bipyridyl-functionalized MCM-41 exhibits a high encapsulating ability, as evidenced by its interaction with a dichloromethane solution of MoO2Cl2(THF)2. A material with a metal loading of 8.3 mass% was obtained. Molybdenum K-edge EXAFS analysis could not substantiate the formation of a tethered complex of the type MoO2Cl2(N–N), but instead indicated the formation of unidentate-bridged entities of the type [O2Mo–X–MoO2] with a metal–metal separation of 3.28 A. The molybdenum-containing MCM was active as a catalyst for the epoxidation of cyclooctene by tert-butyl hydroperoxide. However, this activity is due, at least in part, to leached molybdenum species in solution.

Antimicrobial Action of Carbon Monoxide-Releasing Compounds

ABSTRACT Carbon monoxide (CO) is endogenously produced in the human body, mainly from the oxidation of heme catalyzed by heme oxygenase (HO) enzymes. The induction of HO and the consequent increase in CO production play important physiological roles in vasorelaxation and neurotransmission and in the immune system. The exogenous administration of CO gas and CO-releasing molecules (CO-RMs) has been shown to induce vascular effects and to alleviate hypoxia-reoxygenation injury of mammalian cells. In particular, due to its anti-inflammatory, antiapoptotic, and antiproliferative properties, CO inhibits ischemic-reperfusion injury and provides potent cytoprotective effects during organ and cell transplantation. In spite of these findings regarding the physiology and biology of mammals, nothing is known about the action of CO on bacteria. In the present work, we examined the effect of CO on bacterial cell proliferation. Cell growth experiments showed that CO caused the rapid death of the two pathogenic bacteria tested, Escherichia coli and Staphylococcus aureus, particularly when delivered through organometallic CO-RMs. Of importance is the observation that the effectiveness of the CO-RMs was greater in near-anaerobic environments, as many pathogens are anaerobic organisms and pathogen colonization occurs in environments with low oxygen concentrations. Our results constitute the first evidence that CO can be utilized as an antimicrobial agent. We anticipate our results to be the starting point for the development of novel types of therapeutic drugs designed to combat antibiotic-resistant pathogens, which are widespread and presently a major public health concern.

Highly Chemo- and Regioselective Reduction of Aromatic Nitro Compounds Using the System Silane/Oxo-Rhenium Complexes

The reduction of aromatic nitro compounds to the corresponding amines with silanes catalyzed by high valent oxo-rhenium complexes is reported. The catalytic systems PhMe(2)SiH/ReIO(2)(PPh(3))(2) (5 mol %) and PhMe(2)SiH/ReOCl(3)(PPh(3))(2) (5 mol %) reduced efficiently a series of aromatic nitro compounds in the presence of a wide range of functional groups such as ester, halo, amide, sulfone, lactone, and benzyl. This methodology also allowed the regioselective reduction of dinitrobenzenes to the corresponding nitroanilines and the reduction of an aromatic nitro group in presence of an aliphatic nitro group.

Lewis base adducts of bis-(halogeno)dioxomolybdenum(VI): syntheses, structures, and catalytic applications

Abstract Reaction of solvent substituted MoO2X2(Solv)2 complexes ((Solv)=THF, CH3CN) with mono- and bidentate nitrogen and oxygen donor ligands leads to complexes of the type MoO2X2L2 in nearly quantitative yields at room temperature within a few minutes. The 95 Mo and 17 O NMR data of selected complexes as well as the MoO IR vibrations were used to probe the influence of the ligands on the electronic properties of the metal and the MoO bond. Two complexes have additionally been examined by single crystal X-ray analysis. The activity of the MoO2X2L2 complexes as catalysts in olefin epoxidation with t-butylhydroperoxide as oxidizing agent depends on both the nature of the organic ligand L and the halogeno ligand X. The difference in activity observed between Cl and Br substituted complexes is not very pronounced. In general, the Cl derivatives are more active than their Br analogues. The organic ligands L display a significant influence on the catalytic performance. Complexes with ligands bearing aromatic substituents at N are in all cases, much more active than those bearing aliphatic substituents. The less active complexes can be activated by raising the temperature and extending the reaction time. In all observed cases, these changes produce a significant increase of the product yield.

Organorhenium(VII) and organomolybdenum(VI) oxides: synthesis and application in oxidation catalysis†

Methyltrioxorhenium(VII) has found numerous applications in various catalytic processes. In olefin epoxidation its activity can be enhanced by the addition of aromatic Lewis base nitrogen donor ligands, e.g. pyridines and pyrazoles. Due to the comparatively weak coordination of these ligands, a significant excess has to be used. Therefore the MTO/chiral Lewis base/H 2 O 2 system is not very useful for chiral epoxidations. In contrast to this, dimethyldioxomolybdenum (VI) MoO 2 (CH 3 ) 2 undergoes a significantly stronger interaction with Lewis bases and seems, despite its generally somewhat lower activity, a reasonable candidate for application in chiral epoxidation reactions together with an appropriate chiral Lewis base ligand. Complexes of the type MoO 2 (CH 3 ) 2 L are accessible via MoO 2 X 2 L (X = Cl, Br). These latter compounds are even more active in olefin epoxidation than MoO 2 (CH 3 ) 2 L. Unfortunately, however, all the Mo(VI) complexes mentioned above need t-butyl hydroperoxide as oxidizing agent and do not show activity in the presence of H 2 O 2 .

[MoO2Cl2] as catalyst for hydrosilylation of aldehydes and ketones

The high valent molybdenum-dioxo complex [MoO2Cl2] catalyzes the addition of dimethylphenylsilane to aldehydes and ketones to afford the corresponding dimethylphenylsilyl ethers in quantitative yield.

Reactive Oxygen Species Mediate Bactericidal Killing Elicited by Carbon Monoxide-releasing Molecules

CO-releasing molecules (CO-RMs) were previously shown by us to be more potent bactericides than CO gas. This suggests a mechanism of action for CO-RM, which either potentiates the activity of CO or uses another CO-RM-specific effect. We have also reported that CORM-2 induces the expression of genes related to oxidative stress. In the present study we intend to establish whether the generation of reactive oxygen species by CO-RMs may indeed result in the inhibition of bacterial cellular function. We now report that two CO-RMs (CORM-2 and ALF062) stimulate the production of ROS in Escherichia coli, an effect that is abolished by addition of antioxidants. Furthermore, deletion of genes encoding E. coli systems involved in reactive oxygen species scavenging, namely catalases and superoxide dismutases, potentiates the lethality of CORM-2 due to an increase of intracellular ROS content. CORM-2 also induces the expression of the E. coli DNA repair/SOS system recA, and its inactivation enhances toxicity of CORM-2. Moreover, fluorescence microscopy images reveal that CORM-2 causes DNA lesions to bacterial cells. We also demonstrate that cells treated with CORM-2 contain higher levels of free iron arising from destruction of iron-sulfur proteins. Importantly, we show that CO-RMs generate hydroxyl radicals in a cell-free solution, a process that is abolished by scavenging CO. Altogether, we provide a novel insight into the molecular basis of CO-RMs action by showing that their bactericidal properties are linked to cell damage inflicted by the oxidative stress that they are able to generate.

Molybdenum(VI)cis-dioxo complexes bearing sugar derived chiral Schiff-base ligands: synthesis, characterization, and catalytic applications

Molybdenum(VI)–cis-dioxo complexes bearing sugar derived chiral Schiff-base ligands of general formula MoO2(L)(Solv) have been synthesized (with L = N-salicylidene-D-glucosamine; N-salicylidene-1,3,4,6-tetraacetyl-α-D-glucosamine; N-5-chlorosalicylaldehyde-1,3,4,6-tetraacetyl-α-D-glucosamine; N-salicylaldehyde-1,3,4,6-tetraacetyl-β-D-glucosamine; N-5-chlorosalicylaldehyde-1,3,4,6-tetraacetyl-β-D-glucosamine; N-salicylidene-4,6-O-ethylidene-β-D-glucopyranosylamine, and Solv = methanol or ethanol). Analytical data including IR, 1D- and 2D-NMR, MS and EA are in accord with their descriptions as monometallic compounds with one ligand L and a coordinated solvent molecule. One of the complexes and two of the chiral ligands have been examined by X-ray crystallography. In the case of the sugar –OH groups being protected as acetyl groups, one of them is selectively deacetylated and coordinates to the metal centre during the reaction process. Furthermore, an inversion takes place at the C1 carbon atom. This uncommon behaviour has been examined in some detail. The high catalytic activity of the title compounds for epoxidation is also described as well as the moderate enantiomeric induction of up to 30% ee for cis-β-methyl styrene.

(Dimethyl)dioxomolybdenum(VI) complexes: syntheses and catalytic applications

Abstract Reaction of MoO2Br2S2 complexes [S=THF, CH3CN] with bidentate nitrogen donor ligands (L2) leads to complexes of the type MoO2Br2L2 in good yields, L2=substituted bipyridylphenantroline, 1,4-R2-diazabutadiene and bipyrimidine. Treatment of the latter complexes with Grignard reagents at low temperatures yields complexes of the general formula MoO2(CH3)2L2 and MoO2(C2H5)2(diphenylphenantroline). 1H NMR and IR data are comparatively indifferent to the ligand changes. The 95Mo NMR data of selected complexes reflect the donor capability of the organic ligands. Mass spectroscopy and temperature-dependent 95Mo NMR spectroscopy show a significant stability of the MoN bond. The compound MoO2(CH3)2(bipyrimidine) was additionally examined by single crystal X-ray analysis. The catalytic activity of the MoO2R2L2 complexes in olefin epoxidation with t-butyl hydroperoxide as oxidizing agent is strongly influenced by the nature of the ligand L and its steric bulk in the equatorial plane. The title complexes with a Mo(CH3)2 moiety are slightly less active in catalysis than the MoBr2 precursor compounds. Increase of both reaction time and/or temperature lead to a significant increase in the product yield in all examined cases. At about 90°C catalyst decomposition hampers further product yield increase.