Kinetic and computational analysis of the palladium(II)-catalyzed asymmetric allylic trichloroacetimidate rearrangement: development of a model for enantioselectivity

The asymmetric rearrangement of allylic trichloroacetimidates catalyzed by palladium(II) complexes of the COP family is a powerful method for the preparation of enantioenriched chiral allylic amines from prochiral allylic alcohols. A detailed kinetic analysis of this reaction was performed to elucidate the rate- and enantiodetermining step of this important reaction. The results of these studies support a cyclization-induced rearrangement mechanism and prompted DFT studies (B3LYP/LACVP**+) of C-N bond formation, believed to be the enantiodetermining step of this catalytic cycle. On the basis of these calculations, a model for enantioinduction was developed, in which the planar chirality of the catalyst controls the enantioselectivity. These studies should allow the rational design of more enantioselective catalysts.     

Operationally unsaturated pincer/rhenium complexes form metal carbenes from cycloalkenes and metal carbynes from alkanes

Operationally unsaturated (i.e., 16/18-electron) (PNPR)Re(H)4, where PNPR is N(SiMe2CH2PR2)2, is reactive at 22 degrees C with cyclic olefins. The first observed products are generally (PNPR)Re(H)2(cycloalkylidene), with hydrogenated olefin as the product of hydrogen abstraction from the tetrahydride. The tetrahydride complex with R = tBu generally fails to react (too bulky), that with R = cyclohexyl suffers a (controllable) tendency to abstraction of 3H from one ring, forming an eta3-cyclohexenyl compound, and that with R = iPr generally gives the richest bimolecular reactivity. The cyclic monoolefins studied show distinct reactivity, C6 giving first the carbene and then coordinated cyclohexadiene, C5 giving carbene, then diene, and then eta5-C5H5, C8 giving carbene and then eta2-cyclooctyne, and C12 giving an eta3-allyl. Norbornene gives a pi-complex of the norbornene in thermal equilibrium with its carbene isomer; at 90 degrees C, hydrocarbon ligand Calpha-Cbeta bond cleavage occurs to give, for the first time, a carbyne complex from an internal olefin. Two compounds synthesized here have the formal composition "(PNPR)Re + olefin", and each of these is capable of dehydrogenating the methyl group of a variety of alkanes at 110 degrees C to form (PNP)ReH triple bond (CR).     

Synthesis and structure of cyclopropano-annelated homosesquinorbornene derivatives containing pyramidalized double bonds: evidence for the sterical effect of a cyclopropyl group on the degree of C=C double-bond pyramidalization

[reaction: see text] endo- and exo-2,3,4,7-tetrahydro-1H-1,4-methanobenzocycloheptene-7-carboxylic acid ethyl esters have been synthesized, and their Diels-Alder cycloaddition reactions with maleic anhydride, dimethyl acetylenedicarboxylate and singlet oxygen have been investigated. The X-ray analysis of four adducts indicated the pyramidalization of the central double bond. Density functional theory calculations on the isolated products and model compounds showed excellent agreement between the experimental and theoretical determined butterfly angles. Furthermore, it has been shown that a cyclopropyl group fused to [2.2.2] system decreases significantly the degree of the pyramidalization which is attributed to the steric interactions between the cyclopropyl group and ethano bridge of the norbornene systems. Due to the instability of the bicyclic endoperoxides, their X-ray analysis could not be carried out. DFT calculations on model compounds showed increased bending in the case of the product obtained by the addition of singlet oxygen to endo-2,3,4,7-tetrahydro-1H-1,4-methanobenzocycloheptene-7-carboxylic acid ethyl ester.     

Synthesis of a Lewis acid bearing cyclopentadienyl ligand and its tricarbonylmanganese(I) complex

The synthesis of a bimetallic compound comprising a Lewis acidic organochlorostannane and a transition metal carbonyl is reported. The target complex, [(CO)₃Mn(η⁵-C₅H₄(CH₂)₃SnMe₂Cl)], 2, is prepared in four steps. The final step involves an exchange reaction between [(CO)₃Mn(η⁵-C₅H₄(CH₂)₃SnMe₃)], 1, and SnMe₂Cl₂. Infrared spectroscopy demonstrates no interaction between the Lewis acid and lone pair on the carbonyl oxygen.     

Syntheses and structural characterization of heterometallic bis(pyrazolyl)methane complexes of rhenium and platinum

The new heterometallic complex {μ-1,3,5-[CH(pz)₂]₃C₆H₃}[Re(CO)₃Br][Pt(p-tolyl)₂]₂ has been prepared by reaction of 1 equiv. of the dimer [Pt(p-tolyl)₂(μ-SEt₂)]₂ with the monometallic rhenium precursor {1,3,5-[CH(pz)₂]₃C₆H₃}Re(CO)₃Br, where 1,3,5-[CH(pz)₂]₃C₆H₃ is the tritopic, arene-linked bis(pyrazolyl)methane ligand 1,3,5-tris[bis(1-pyrazolyl)methyl]benzene. Similarly, the heterometallic complex {μ-1,3,5-[CH(pz)₂]₃C₆H₃}[Re(CO)₃Br]₂[Pt(p-tolyl)₂] has been made by the reaction of the dirhenium compound {μ-1,3,5-[CH(pz)₂]₃C₆H₃}[Re(CO)₃Br]₂ and one-half of an equivalent of [Pt(p-tolyl)₂(μ-SEt₂)]₂. X-ray crystallographic studies of the new compounds reveal significant noncovalent interactions in their molecular and supramolecular structures.     

Identification and quantitation of phenylalanine, tyrosine and dihydroxyphenylalanine in the thoracic nervous system of the locust, Schistocerca gregaria, by gas chromatography-negative-ion chemical ionisation mass spectrometry

Phenylalanine, tyrosine and dihydroxyphenylalanine (DOPA) were identified unambiguously and quantitatively determined in single ventral thoracic nerve cords from the locust, Schistocerca gregaria, by gas chromatography-negative-ion chemical ionisation mass spectrometry. Deuterium-labelled analogues of each compound were added to a single ventral thoracic nerve cord in hydrochloric acid; the tissue was homogenised and the suspension centrifuged. The remaining hydrochloric acid was eliminated azeotropically by repeated additions of acetonitrile followed by evaporation under a stream of nitrogen and the resultant residue derivatised by reaction with hexafluoroisopropanol and pentafluoropropionic anhydride. Under negative-ion chemical ionisation conditions, the hexafluoroisopropanol-pentafluoropropionyl derivatives produced characteristic ions which were sufficiently abundant to be suitable for selected-ion monitoring. This method is highly specific and gave a limit of detection below the nanogram level. The amounts of phenylalanine, tyrosine and DOPA in a single ventral thoracic nerve cord were, respectively, 194 +/- 81, 347 +/- 88 and 11 +/- 11 ng per tissue.     

Amplified detection of nucleic acids and proteins using an isothermal proximity CRISPR Cas12a assay

Herein, we describe an isothermal proximity CRISPR Cas12a assay that harnesses the target-induced indiscrimitive single-stranded DNase activity of Cas12a for the quantitative profiling of gene expression at the mRNA level and detection of proteins with high sensitivity and specificity. The target recognition is achieved through proximity binding rather than recognition by CRISPR RNA (crRNA), which allows for flexible assay design. A binding-induced primer extension reaction is used to generate a predesigned CRISPR-targetable sequence as a barcode for further signal amplification. Through this dual amplification protocol, we were able to detect as low as 1 fM target nucleic acid and 100 fM target protein isothermally. The practical applicability of this assay was successfully demonstrated for the temporal profiling of interleukin-6 gene expression during allergen-mediated mast cell activation.

Herein, we develop an isothermal proximity CRISPR Cas12a assay that harnesses the target-induced collateral cleavage activity of Cas12a for the quantitative profiling of gene expression and detection of proteins with high sensitivity and specificity.