Visible‐Light‐Induced CO Release from a Therapeutically Viable Tryptophan‐Derived Manganese(I) Carbonyl (TryptoCORM) Exhibiting Potent Inhibition against E. coli

The first visible‐light‐activated carbon‐monoxide‐releasing molecule (CO‐RM) to exhibit a potent effect against Escherichia coli is described. The easily prepared tryptophan‐derived manganese‐containing complex (TryptoCORM) released 1.4 moles of CO at 465 nm, and 2 moles at 400 nm. A comprehensive synthetic, mechanistic and microbiological study into the behaviour of TryptoCORM is reported. The complex is thermally stable (i.e., does not release CO in solution in the absence of light), shows low toxicity against mammalian cells and releases tryptophan on photoinduced degradation, all of which point to TryptoCORM being therapeutically viable.     

Synthesis and structures of photoactive manganese–carbonyl complexes derived from 2‐(pyridin‐2‐yl)‐1,3‐benzothiazole and 2‐(quinolin‐2‐yl)‐1,3‐benzothiazole

PhotoCORMs (photo‐active CO‐releasing molecules) have emerged as a class of CO donors where the CO release process can be triggered upon illumination with light of appropriate wavelength. We have recently reported an Mn‐based photoCORM, namely [MnBr(pbt)(CO)₃] [pbt is 2‐(pyridin‐2‐yl)‐1,3‐benzothiazole], where the CO release event can be tracked within cellular milieu by virtue of the emergence of strong blue fluorescence. In pursuit of developing more such trackable photoCORMs, we report herein the syntheses and structural characterization of two Mn^I–carbonyl complexes, namely fac‐tricarbonylchlorido[2‐(pyridin‐2‐yl)‐1,3‐benzothiazole‐κ²N ,N ′]manganese(I), [MnCl(C₁₂H₈N₂S)(CO)₃], (1), and fac‐tricarbonylchlorido[2‐(quinolin‐2‐yl)‐1,3‐benzothiazole‐κ²N ,N ′]manganese(I), [MnCl(C₁₆H₁₀N₂S)(CO)₃], (2). In both complexes, the Mn^I center resides in a distorted octahedral coordination environment. Weak intermolecular C—H…Cl contacts in complex (1) and Cl…S contacts in complex (2) consolidate their extended structures. These complexes also exhibit CO release upon exposure to low‐power broadband visible light. The apparent CO release rates for the two complexes have been measured to compare their CO donating capacity. The fluorogenic 2‐(pyridin‐2‐yl)‐1,3‐benzothiazole and 2‐(quinolin‐2‐yl)‐1,3‐benzothiazole ligands provide a convenient way to track the CO release event through the `turn‐ON' fluorescence which results upon de‐ligation of the ligands from their respective metal centers following CO photorelease.     

A Structurally-Tunable 3-Hydroxyflavone Motif for Visible Light-Induced Carbon Monoxide-Releasing Molecules (CORMs)

Molecules that can be used to deliver a controlled amount of carbon monoxide (CO) have the potential to facilitate investigations into the roles of this gaseous molecule in biology and advance therapeutic treatments. This has led to the development of light-induced CO-releasing molecules (photoCORMs). A goal in this field of research is the development of molecules that exhibit a combination of controlled CO release, favorable biological properties (e.g., low toxicity and trackability in cells), and structural tunability to affect CO release. Herein, we report a new biologically-inspired organic photoCORM motif that exhibits several features that are desirable in a next-generation photoCORM. We show that 3-hydroxyflavone-based compounds are easily synthesized and modified to impart changes in absorption features and quantum yield for CO release, exhibit low toxicity, are trackable in cells, and can exhibit both O₂-dependent and -independent CO release reactivity.     

Rapid green and blue light‐induced CO release from bromazepam Mn(I) and Ru(II) carbonyls: synthesis,density functional theory and biological activity evaluation

Two new photoactivatable carbon monoxide‐releasing molecules (CORMs), fac ‐[Mn(CO)₃(BZM)Br] ( 1 ) and [RuCl₂(BZM)(CO)₂] ( 2 ), derived from the anti‐anxiety drug bromazepam (BZM) and capable of rapid release of CO upon the illumination with light‐emitting diode (LED) source light (470–525 nm) have been synthesized and characterized. The photo‐delivery of CO to myoglobin solution could be achieved via the illumination of 1 at 525 nm for 10 min or at 470 nm for 1 min. The addition of water to a dimethylsulfoxide (DMSO) solution of 1 increases its stability, but it decreases the rate of the CO‐releasing process. CORM 2 behaves as a good visible photoCORM, whereby its two CO molecules are released within 10 min upon exposure to LED light source at 470 nm in DMSO. The illumination profile of 2 was also examined using solution infrared spectroscopy. The cis /trans stereochemistry around the Ru(II) ion was determined using quantum chemical calculations. The formation of photoCORMs leads to an improvement in the toxicity of BZM against tested microbes.     

Theoretical study of the mechanism of CH2CO + CN reaction

The potential energy surface information of the CH₂CO + CN reaction is obtained at the B3LYP/6‐311+G(d,p) level. To gain further mechanistic knowledge, higher‐level single‐point calculations for the stationary points are performed at the QCISD(T)/6‐311++G(d,p) level. The CH₂CO + CN reaction proceeds through four possible mechanisms: direct hydrogen abstraction, olefinic carbon addition–elimination, carbonyl carbon addition–elimination, and side oxygen addition–elimination. Our calculations demonstrate that R→IM1→TS3→P3: CH₂CN + CO is the energetically favorable channel; however, channel R→IM2→TS4→P4: CH₂NC + CO is considerably competitive, especially as the temperature increases (R, IM, TS, and P represent reactant, intermediate, transition state, and product, respectively). The present study may be helpful in probing the mechanism of the CH₂CO + CN reaction. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

A Red-Light-Driven CO-Releasing Complex: Photoreactivities and Excited-State Dynamics of Highly Distorted Tricarbonyl Rhenium Phthalocyanines

A complex comprising one [Re(CO)₃]⁺ unit and a phthalocyanine (Pc) ligand ( Re₁Pc ) is shown to function as a photo-induced CO-releasing molecule (photoCORM) in the presence of O₂ and a coordinative solvent under irradiation with red light, which can deeply penetrate living tissues. Transient absorption spectroscopic measurements indicate very short excited-state lifetimes and ultrafast intersystem crossing for Re₁Pc and Re₂Pc , which contains two [Re(CO)₃]⁺ units. The excited-state properties are ascribed to efficient spin–orbit coupling and large Franck–Condon factors originating from the complexes’ distorted structures, that is, unsymmetric coordination of [Re(CO)₃]⁺ unit(s), one of which was confirmed by single-crystal X-ray analysis of a symmetrically substituted Pc with two [Re(CO)₃]⁺ units. Re₁Pc represents a promising red-light-driven photoCORM that can be applied in biological environments or therapeutic applications.     

Precision of a diode-array spectrophotometer

Modern diode-array UV-visible spectrophotometers can record the entire spectrum of a sample in a fraction of a second. The operating procedure usually followed to obtain more reliable spectra involves scanning several spectra over a preset time T_i known as the integration time and averaging them. In order to establish how the selection of T_i and wavelength affect the repeatability and reproducibility of results, replicate spectra were recorded at different integration times and wavelengths. The results showed that both parameters influence the precision. The absorbance was also affected by T_i, to an extent that increased with decreasing wavelength. The best relative precision was accomplished over the absorbance range 0.8–1.     

Relation between coordination geometry and stereoelectronic properties in DFT models of the CO-inhibited [FeFe]-hydrogenase cofactor

In this work DFT has been used to characterize model complexes structurally related to the CO-inhibited form (Hox-CO) of [FeFe]-hydrogenases.The investigation of a recently synthesized diiron complex ([Fe₂{MeSCH₂C(Me)(CH₂S)₂}(CN)₂(CO)₄]⁻, [M. Razavet, S.J. Borg, S.J. George, S.P. Best, S.A. Fairhurst, C.J. Pickett, Chem. Commun. 2002, 700-701]) that closely reproduces most features of the inhibited enzyme cofactor, led to the conclusion that the computation of DFT energy differences, as well as the comparison between computed and experimental IR and EPR spectra, does not allow to confidently distinguish among isomers differing for the position of CO and CN ligands, an issue which is relevant not only to fully understand the mechanism of CO-mediated inhibition of the enzyme, but more generally to further understand the factors affecting substrates coordination to the enzyme active site.The latter observation prompted us to probe the effect of the electronic properties of ligands on the structural features of a series of [Fe₂(SCH₂XCH₂S)(CN)₂(CO)₃(L)]ⁿ⁻ complexes related to the Hox-CO form of the enzyme but differing for the nature of L (CO, (CH₃)₂S, CH₃S⁻, CH₃O⁻ and F⁻) and X (CH₂, NH and O). Results revealed that the electronic properties of ligands, as well as the nature of the chelating group bridging the two iron atoms, can affect the coordination geometry of the distal metal center. In particular, it turned out that the inclusion of hard ligands in the Fe coordination sphere could be a viable strategy to selectively favour isomers featuring two CO groups trans to each other. On the other hand, the substitution of propanedithiolate with a di(thiomethyl)amine residue led to the selective stabilization of structures featuring a CN ligand in trans to the μ-CO group, thanks to the formation of an intramolecular hydrogen bond. The relevance of these DFT results for the design of novel biomimetic models of the CO-inhibited [FeFe]-hydrogenases active site is discussed.     

Über Chalkogenolate. 136 [1]. Alkylester der Cyanoameisensäure und der Cyanomonothioameisensäure

On Chalcogenolates. 136. Alkyl Esters of Cyanoformic Acid and of Cyanomonothioformic Acid By use of the phase transfer catalyst 18-crown-6 the esters CH₃O—CO—CN, C₂H₅O—CO—CN, C₂H₅S—CO—CN, and ⁿC₃H₇S—CO—CN have been prepared by reaction of the corresponding chloro compound with potassium cyanide. The prepared compounds have been characterized by means of electron absorption, infrared, nuclear magnetic resonance (¹H and ¹³C), and mass spectra.     

Cr(CO)5(CNCN), a complex in which the coordinated CN group of isocyanogen binds and vibrates like a CO ligand

The IR and Raman spectra have been determined of the products formed by low-temperature (−20°C) replacement of 2-MeTHF (2-methyltetrahydrofuran) in photochemically produced Cr(CO)₅(2-MeTHF) by isocyanogen, CNCN. The IR spectra are interpreted in terms of the formation of an isonitrile and a nitrile complex, Cr(CO)₅(CNCN) and Cr(CO)₅(NCNC). A detailed study of the IR and Raman spectra of Cr(CO)₅(CNCN), which was formed in large excess, reveals that the coordinating CN group of CNCN has coordinating and vibrational properties almost identical to those of the CO ligands in this complex.     

Photolysis of poly(ethylene terephthalate)

The photolysis of poly(ethylene terephthalate) films was studied in vacuo with light of wavelengths 2537 and 3130 A. A very stable filter system which cuts out the 3025 A. line was developed to isolate 3130 A. from a mercury spectrum. Despite the fact that the penetration of 2537 A. light was limited to a depth of a ca. 10³ A. whereas 3130 A. light was more uniformly absorbed it was possible to demonstrate that the quantum yields for CO and CO₂ formation were in agreement for the two wavelengths. Quantum yields for fractures and crosslinks were estimated by sol-gel analysis. An absorption maximum which develops near 13 μ after exposure of poly(ethylene terephthalate) to light or γ-rays was attributed to the formation of groups formed by elimination of CO and CO₂. ESR spectra for trapped radicals were tentatively assigned to the components p-C₆H₃· and ·O? CH₂? CH₂? . It is suggested that the former radicals combine to form crosslinks. Quantum yields (× 10⁴) with 3130 A. light are: CO, 6; CO₂, 2; crosslinks, 5.5; trapped radicals, 1.5; With 2537 A. light, quantum yields are: CO, 6–9; CO₂, 2–3; the network formed was not characterized as to crosslinks and fractures; trapped radicals were observed to exist but not determined.     

Theoretical study on the reaction mechanism of CN radical with ketene

The bimolecular single collision reaction potential energy surface of CN radical with ketene (CH2CO) was investigated by means of B3LYP and QCISD(T) methods. The calculated results indicate that there are three possible channels in the reaction. The first is an attack reaction by the carbon atom of CN at the carbon atom of the methylene of CH2CO to form the intermediate NCCH2CO followed by a rupture reaction of the C-C bond combined with -CO group to the products CH2CN CO. The second is a direct addition reaction between CN and CH2CO to form the intermediate CH2C(O)CN followed by its isomerization into NCCH2CO via a CN-shift reaction, and subsequently, NCCH2CO dissociates into CH2CN CO through a CO-loss reaction. The last is a direct hydrogen abstraction reaction of CH2CO by CN radical. Because of the existence of a 15.44 kJ/mol reaction barrier and higher energy of reaction products, the path can be ruled out as an important channel in the reaction kinetics. The present theoretical computation results, which give an available suggestion on the reaction mechanism, are in good agreement with previous experimental studies.     

Multiwavelength Raman spectroscopy analysis of a large sampling of disordered carbons extracted from the Tore Supra tokamak

Disordered carbon often exhibit a complex Raman spectrum, with four to six components. Here, a large variety of disordered carbons, forming a collection of samples with a great variety of structures, are analyzed using multi-wavelength Raman microscopy (325.0, 514.5, 785.0 nm). They allow us to extend Raman behaviour known for nano-crystalline graphite to amorphous carbons, (dependence with the excitation wavelength) and other known for amorphous carbons to nano-crystalline graphite, (differentiation of the smallest cluster size probed using different excitation wavelengths). Experimental spectra were compared to simulated spectra, built using known laws, to evidence a new source of broadening.     

Synthesis and characterization of tungsten carbonyl complexes containing N-methyl substituted urea and thiourea ligands

Six new mixed-ligand tungsten carbonyl complexes containing N-methyl substituted urea and thiourea of the type W(CO)₄[RCH₂N-(C=X)NH₂] where X?=?O or S and R?=?morpholine, piperidine and diphenylamine are reported. These have been prepared by refluxing hexacarbonyl tungsten(0) with corresponding ligands in THF to produce cis-disubstituted products, [(L-L)W(CO)₄] where L-L?=?a chelating bidentate ligand, morpholinomethyl urea (MMU), morpholinomethyl thiourea (MMTU), piperidinomethyl urea (PMU), piperidinomethyl thiourea (PMTU), diphenylaminomethyl urea (DAMU) and diphenylaminomethyl thiourea (DAMTU). The compounds have been characterized by elemental analysis, IR, electronic and ¹³C NMR spectra, magnetic moments and conductivity measurements. The IR spectra suggests that in all the complexes, the ligands are bidentate chelating, coordinating the metal through carbonyl oxygen or thiocarbonyl sulphur and the ring nitrogen or tert-nitrogen of diphenylamine. The CO force constants and CO–CO interaction constants for these derivatives have also been calculated using Cotton–Kraihanzel secular equations, which indicate poor π-bonding ability of the ligands. ¹³C NMR and electronic spectra reveal loss of cis-carbonyl ligands to produce cis-disubstituted tetracarbonyl derivatives. Molecular modeling studies have been carried out using Hyperchem release 7.52 which suggest a distorted octahedral geometry for these complexes.     

Exploring the Effect of Ligand Structural Isomerism in Langmuir–Blodgett Films of Chiral Luminescent EuIII Self‐Assemblies

Here we have investigated the influence of the antenna group position on both the formation of chiral amphiphilic Eu^III‐based self‐assemblies in CH₃CN solution and, on the ability to form monolayers on the surface of quartz substrates using the Langmuir–Blodgett technique, by changing from the 1‐naphthyl ( 2(R) , 2(S) ) to the 2‐naphthyl ( 1(R) , 1(S) ) position. The evaluation of binding constants of the self‐ assemblies in CH₃CN solution was achieved using conventional techniques such as UV/Visible and luminescence spectroscopies along with more specific circular dichroism (CD) spectroscopy. The binding constants obtained for EuL , EuL₂ and EuL₃ species in the case of 2‐naphthyl derivatives were comparable to those obtained for 1‐naphthyl derivatives. The analysis of the changes in the CD spectra of 1(R) and 1(S) upon addition of Eu^III not only allowed us to evaluate the values of the binding constants but the resulting recalculated spectra may also be used as fingerprints for assignment of the chiral self‐assembly species formed in solution. The obtained monolayers were predominantly formed from EuL₃ (≈85 %) with the minor species present in ≈15 % EuL₂ .     

Far infrared spectra,vibrational assignment and normal coordinate analysis of the tricyanomethanideion

Far infrared spectra of the tricyanomethanide ion C(CN)₃^? in solution and in the solid state have been investigated. The results allow a complete vibrational assignment to be made. A normal coordinate analysis has been carried out, the results of which are compatible with the existence of some double bond character in the C-C bonds of C(CN)₃^?.     

Ab initio quantum chemical studies of reaction mechanism for CN with CH2CO

Six product channels have been found in the association reaction of CN + CH₂CO, and a variety of possible complexes and saddle points along the minimum energy reaction paths have been characterized at the UMP2(full)/6‐31G(d) level. The dominant reaction channels are the production of CH₂CN + CO and CH₂NC + CO. The isomerization and dissociation reactions of the major products of CH₂CN and CH₂NC have been investigated using the G2MP2 level. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Electron impact ionization mass spectra of some substituted dipyrido[1,2-a:4,3-d]pyrimidinones

The electron impact ionization mass spectra of dipyrido [1,2-a:4,3-d]pyrimidinones are strongly influenced by the degree of aromaticity of the fused rings. The molecular ions of the compounds are fairly stable. The main routes of fragmentation involve formation of the [M – H]⁺ ion and loss of substituents, H₂CN˙, CO and alkyl radicals.     

Elektronenreiche übergangsmetallkomplexe : IV. Dien-bis(phosphin)-molybdändicarbonyle

Dienes can replace the acetonitrile in (CH₃CN)₂Mo(PBu₃)₂,(CO)₂ or acetoni- trile and the one phosphine trans to the CO group in (CH₃CN)Mo(PBu₃)₃(CO)₂ under mild conditions. IR-, H NMR, ¹³C NMR and electronic spectra of the new (diene)Mo(PBu₃)₂(CO)₂ complexes are discussed and compared with similar compounds of other transition metals.     

Resonance capture of electrons by cyclopentadienyltricarbonylmanganese and -rhenium derivatives

Negative ion mass spectra of cyclopentadienyltricarbonylmanganese and-rhenium derivatives RC₅H₄M(CO)₃ (R=H, CN, COOH, COMe, COOMe, CH₂OH, CHO; M=Mn, Re) were studied. The subsequent detachment of carbonyl groups is the main process of the fragmentation of these compounds under the conditions of the resonance capture of electrons. On going fron the rhenium complexes to manganese derivatives, the maxima of the yields of the ions [M-nCO]⁻ (n=1–3) shift to the lower energy region indicating that the stability of the Re−CO bond is higher than that of Mn−CO. The average lifetimes of the molecular negative ions relative to the autodetachment of an electron (τ_a) and to dissociation (τ_d) were measured. It was found that electron-accepting substituents increase the τ_a value and decrease τ_d. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1161–1164, June, 1997.