Development of a new and practical route to chiral 3,4-disubstituted cyclopentanones: asymmetric alkylation and intramolecular cyclopropanation as key C-C bond-forming steps

An efficient and practical asymmetric synthesis of (+)-trans-3-hydroxymethyl-4-(3-fluorophenyl)cyclopentanone (1) is described. An asymmetric Mo-catalyzed alkylation reaction was used to establish the first stereocenter and a Cu-catalyzed intramolecular diastereoselective cyclopropanation reaction was used to set the second stereocenter. The last step involved a one-pot ring-opening/deprotection/hydrolysis/decarboxylation sequence that furnished the desired product in good yield.     

Examination of segmental average mass spectra from liquid chromatography–tandem mass spectrometric (LC–MS/MS) data enables screening of multiple types of protein modifications

It has been observed that a modified peptide and its non-modified counterpart, when analyzed with reverse phase liquid chromatography, usually share a very similar elution property [1–3]. Inasmuch as this property is common to many different types of protein modifications, we propose an informatics-based approach, featuring the generation of segmental average mass spectra (^saMS), that is capable of locating different types of modified peptides in two-dimensional liquid chromatography–mass spectrometric (LC–MS) data collected for regular protease digests from proteins in gels or solutions. To enable the localization of these peptides in the LC–MS map, we have implemented a set of computer programs, or the ^saMS package, that perform the needed functions, including generating a complete set of segmental average mass spectra, compiling the peptide inventory from the Sequest/TurboSequest results, searching modified peptide candidates and annotating a tandem mass spectrum for final verification. Using ROCK2 as an example, our programs were applied to identify multiple types of modified peptides, such as phosphorylated and hexosylated ones, which particularly include those peptides that could have been ignored due to their peculiar fragmentation patterns and consequent low search scores. Hence, we demonstrate that, when complemented with peptide search algorithms, our approach and the entailed computer programs can add the sequence information needed for bolstering the confidence of data interpretation by the present analytical platforms and facilitate the mining of protein modification information out of complicated LC–MS/MS data.     

Singlet oxygen production by Peptide-coated quantum dot-photosensitizer conjugates

Peptide-coated quantum dot-photosensitizer conjugates were developed using novel covalent conjugation strategies on peptides which overcoat quantum dots (QDs). Rose bengal and chlorin e6, photosensitizers (PSs) that generate singlet oxygen in high yield, were covalently attached to phytochelatin-related peptides. The photosensitizer-peptide conjugates were subsequently used to overcoat green- and red-emitting CdSe/CdS/ZnS nanocrystals. Generation of singlet oxygen could be achieved via indirect excitation through F?rster (fluorescence) resonance energy transfer (FRET) from the nanocrystals to PSs, or by direct excitation of the PSs. In the latter case, by using two color excitations, the conjugate could be simultaneously used for fluorescence imaging and singlet oxygen generation. Singlet oxygen quantum yields as high as 0.31 were achieved using 532-nm excitation wavelengths.     

Novel butterfly tungsten-osmium carbido cluster Complexes from the reaction of Os3(CO)10(NCME)2 CPW(CO)3(CH2SMe)

Condensation of be triosmium acetonitrile complex Os₃(CO)₁₀(NCMe)₂ with the sulfido complex CpW(CO)₃(CH₂SMe) in refluxing THF solution produced three sulfur-containing compounds Os₃(C0)₁₀)(µ-H)(µ-SMe) (1), Os₃(CO)₁₁ [S(Me)CH₂W(CO)₃Cp] (2) and CpWOs₃(CO)₁₂(µ-CH₂)(µ-SMe) (3). Clusters 2 and 3 were products involving a 1:1 combination of starting materials and were characterized by X-ray diffraction studies. Crystals of 2 belongs to monoclinic space group P 2₁ /c witha=8.418(2),b = 11.912(2),c = 28.288 Å,=97.64(2)°,Z=4;R _F=0.044,R _W,=0.044. Crystal dara far 3: space group P 2₁/e,a 18.156(4).b=9.255(6),c = 15.347(4) Å. = 103.49(2)°,Z = 4;R _F -=0.047,R _W = 0.045. Upon thermolysis in toluene, the methylene cluster 3 released CO and induced C-H bond activation to afford two tetrametallic carbido clusters with formula CPWOS₃(CO)₉(µ₄-C)(µ-H)₂(µ-SMe) (4) and CPWOs₃(CO)₁₁(µ₄-C)(µ-SMe) (5) as the principle products. The first complex possesses a butterfly framework encapsulating a µ₄-C ligmd and a µ-SMe ligand linking a W-Os edge, whereas the second product adopts a puckered, cyclic arrangement of WOs₃ metal atoms with µ-SMe ligand located on a nonbonding Os-Os vector. Complex4 crystallizes in monoclinic space group P 2₁ /c witha=15.633(4) Å,b = 8.699 (3) Å,c=15.422(4) Å,=93.12(2)=°, Z=4,R=0.036,R _W =0.034 for 2780 observed reflections. Crystal data for5: space groupP nma,a=14.542(3),b=13.710(6),c=11.758(3) Å.Z=4,R _F =0.038,R _W = 0.037 for 1826 observed reflections. A variable temperature¹H NMR study was also presented to demonstrate the solution fluxionality of5.     

Dihydrogen binding to isostructural s = (1)/(2) and s = 0 cobalt complexes

Two isostructural, nonclassical Co(H(2)) complexes are prepared from their Co(N(2)) precursors using tris(phosphino)silyl and tris(phosphino)borane ancillary ligands. Comproportionation of CoBr(2) and Co metal in the presence of TPB (tris-(o-diisopropylphophinophenyl)borane) gives (TPB)CoBr (4). One-electron reduction of 4 triggers N(2) binding to give (TPB)Co(N(2)) (2-N(2)) which is isostructural to previously reported [SiP(3)]Co(N(2)) (1-N(2)) ([SiP(3)] = tris-(o-diisopropylphosphinophenyl)silyl). Both 1-N(2) and 2-N(2) react with 1 atm H(2) to generate thermally stable H(2) complexes 1-H(2) and 2-H(2), respectively. Both complexes are characterized by a suite of spectroscopic techniques in solution and by X-ray crystallography. The H(2) and N(2) ligands in 2-H(2) and 2-N(2) are labile under ambient conditions and the binding equilibria are observable by temperature-dependent UV/vis. A van't Hoff analysis allows for the ligand binding energetics to be determined (H(2): ΔH(o) = -12.5(3) kcal mol(-1) and ΔS(o) = -26(3) cal K(-1) mol(-1); N(2): ΔH(o) = -13.9(7) kcal mol(-1) and ΔS(o) = -32(5) cal K(-1) mol(-1)).