Palladium-catalyzed carbonylation of aryl bromides using microwave heating and bis[CP-Fe(II)-(CO)2] as a carbon monoxide source

A palladium-catalyzed, microwave assisted carbonylative reaction is described for the synthesis of benzamides from aryl bromides and primary or secondary amines. The developed method uses bis(cyclopentadienyldicarbonyliron) as a solid source of carbon monoxide to produce a diverse set of secondary and tertiary amides in 42–82% yield.     

Spontaneous CO Release from RuII(CO)2–Protein Complexes in Aqueous Solution,Cells, and Mice

We demonstrate that Ru^II(CO)₂–protein complexes, formed by the reaction of the hydrolytic decomposition products of [fac‐RuCl(κ²‐H₂NCH₂CO₂)(CO)₃] (CORM‐3) with histidine residues exposed on the surface of proteins, spontaneously release CO in aqueous solution, cells, and mice. CO release was detected by mass spectrometry (MS) and confocal microscopy using a CO‐responsive turn‐on fluorescent probe. These findings support our hypothesis that plasma proteins act as CO carriers after in vivo administration of CORM‐3. CO released from a synthetic bovine serum albumin (BSA)–Ru^II(CO)₂ complex leads to downregulation of the cytokines interleukin (IL)‐6, IL‐10, and tumor necrosis factor (TNF)‐α in cancer cells. Finally, administration of BSA–Ru^II(CO)₂ in mice bearing a colon carcinoma tumor results in enhanced CO accumulation at the tumor. Our data suggest the use of Ru^II(CO)₂–protein complexes as viable alternatives for the safe and spatially controlled delivery of therapeutic CO in vivo.     

Direct Measurement of the Visible to UV Photodissociation Processes for the PhotoCORM TryptoCORM

PhotoCORMs are light-triggered compounds that release CO for medical applications. Here, we apply laser spectroscopy in the gas phase to TryptoCORM, a known photoCORM that has been shown to destroy Escherichia coli upon visible-light activation. Our experiments allow us to map TryptoCORM's photochemistry across a wide wavelength range by using novel laser-interfaced mass spectrometry (LIMS). LIMS provides the intrinsic absorption spectrum of the photoCORM along with the production spectra of all of its ionic photoproducts for the first time. Importantly, the photoproduct spectra directly reveal the optimum wavelengths for maximizing CO ejection, and the extent to which CO ejection is compromised at redder wavelengths. A series of comparative studies were performed on TryptoCORM-CH₃CN which exists in dynamic equilibrium with TryptoCORM in solution. Our measurements allow us to conclude that the presence of the labile CH₃CN facilitates CO release over a wider wavelength range. This work demonstrates the potential of LIMS as a new methodology for assessing active agent release (e.g. CO, NO, H₂S) from light-activated prodrugs.     

Spontaneous CO Release from RuII(CO)2–Protein Complexes in Aqueous Solution,Cells, and Mice

We demonstrate that Ru^II(CO)₂–protein complexes, formed by the reaction of the hydrolytic decomposition products of [fac‐RuCl(κ²‐H₂NCH₂CO₂)(CO)₃] (CORM‐3) with histidine residues exposed on the surface of proteins, spontaneously release CO in aqueous solution, cells, and mice. CO release was detected by mass spectrometry (MS) and confocal microscopy using a CO‐responsive turn‐on fluorescent probe. These findings support our hypothesis that plasma proteins act as CO carriers after in vivo administration of CORM‐3. CO released from a synthetic bovine serum albumin (BSA)–Ru^II(CO)₂ complex leads to downregulation of the cytokines interleukin (IL)‐6, IL‐10, and tumor necrosis factor (TNF)‐α in cancer cells. Finally, administration of BSA–Ru^II(CO)₂ in mice bearing a colon carcinoma tumor results in enhanced CO accumulation at the tumor. Our data suggest the use of Ru^II(CO)₂–protein complexes as viable alternatives for the safe and spatially controlled delivery of therapeutic CO in vivo.     

Iron(I)-Based Carbonyl Complexes with Bridging Thiolate Ligands as Light-Triggered CO Releasing Molecules (photoCORMs)

A series of thiolate ligands were used to synthesize diiron(I) hexacarbonyl bis(thiolates) for structural studies. Conversion of the corresponding thiols with triiron(0) dodecacarbonyl yields complexes of the type [{(CO)₃Fe(μ-SR)}₂] [R = C₆H₅ ( 1 ), C₆H₄-4-CH₃ ( 2 ), C₆H₄-4-F ( 3 ), C₆F₅ ( 4 ), C₆H₄-4-CF₃ ( 5 ), C₆H₂-2,4,6-(CH₃)₃ ( 6 ), CH₂–C₆H₄-4-Cl ( 7 )]. These complexes were isolated and fully characterized, including X-ray crystal structures of complexes 2 – 7 . The bridging thiolate ligands mainly influence the Fe–CO bond which is trans-positioned to the second iron(I) center. In solution, the anti-isomer with one axially and one equatorially oriented thiolate is the major species; severe steric strain induced by mesityl groups only allows the formation of syn-endo-isomeric molecules of 7 . Furthermore, light-induced CO release at solid material at the three representative complexes 1 , 3 , and 6 verify suitability as photoCORMs.