CO Reductive Oligomerization by a Divalent Thulium Complex and CO2-Induced Functionalization

To date, only a very limited number of complexes based on low-valent main group or f-block elements have allowed the reductive coupling of CO molecules to afford multicarbon oxygenates. Herein, we described the reactivity of the divalent thulium complex [Tm(Cpttt)2] (Cpttt = 1,2,4-tris(tert-butyl)cyclopentadienyl) towards CO, leading to selective CO reductive dimerization and trimerization into ethynediolate (C2) and ketenecarboxylate (C3) complexes, respectively. Quantum chemical (DFT) calculations were performed to shed light on the elementary steps of CO homologation and support a stepwise chain growth from the C2 to the C3 product upon addition of extra CO. The attempted decoordination of the ethynediolate frag-ment by treatment with Me3SiI led to dimerization and rearrangement into a 3,4-dihydroxyfuran-2-one complex. Investiga-tion of the reactivity of the C2 and C3 complexes towards other electrophiles led to unusual functionalization reactions: while the reaction of the ketenecarboxylate C3 complex with electrophiles yielded new multicarbon oxygenated complexes, the addition of CO2 to the ethynediolate C2 complex resulted in the formation of a very reactive intermediate, allowing C–H activation of the toluene solvent. This original intermolecular reactivity corresponds to an unprecedented functionalization of CO-derived ligands, which is induced by CO2.

Frustrated Lewis Pair Stabilized Phosphoryl Nitride (NPO), a Mono Phosphorus Analogue of Nitrous Oxide (N2O)

Phosphoryl nitride (NPO) is a highly reactive intermediate, and its chemistry has only been explored under matrix isolation conditions so far. Here we report the synthesis of an anthracene (A) and phosphoryl azide-based molecule (N3P(O)A) that acts as a molecular synthon of NPO. Experimentally, N3P(O)A dissociates thermally with a first order kinetic half-life that is associated with an activation enthalpy of ΔH⧧ = 27.5 ± 0.3 kcal mol–1 and an activation entropy of ΔS⧧ = 10.6 ± 0.3 cal mol–1 K–1 that are in good agreement with calculated DLPNO-CCSD(T)/cc-pVTZ//PBE0-D3(BJ)/cc-pVTZ energies. In solution N3P(O)A undergoes Staudinger reactivity with tricyclohexylphosphine (PCy3) and subsequent complexation with tris(pentafluorophenyl)borane (B(C6F5)3, BCF) to form Cy3P-NP(A)O-B(C6F5)3. Anthracene is cleaved off photochemically to form the frustrated Lewis pair (FLP) stabilized NPO complex Cy3P⊕-N=P-O-B⊖(C6F5)3. Intrinsic Bond Orbital (IBO) analysis suggests that the adduct is zwitterionic, with a positive and negative charge localized on the complexing Cy3P and BCF, respectively.

Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.

On the Activation of PhICl2 with Pyridine

<div>It has been previously proposed that pyridines can activate PhICl2 by displacing a chloride and forming the [PhI(Pyr)(Cl)]+ cation as a reactive intermediate. Here we show that pyridine does not displace chloride, but rather forms a weak complex with the iodine via halogen bonding along the C-I bond axis. This interaction is investigated by NMR, structural, charge density and theoretical investigations, which all indicate the pyridine does not activate PhICl2 as proposed.</div><div><br></div>

On the Activation of PhICl2 with Pyridine

<div>It has been previously proposed that pyridines can activate PhICl2 by displacing a chloride and forming the [PhI(Pyr)(Cl)]+ cation as a reactive intermediate. Here we show that pyridine does not displace chloride, but rather forms a weak complex with the iodine via halogen bonding along the C-I bond axis. This interaction is investigated by NMR, structural, charge density and theoretical investigations, which all indicate the pyridine does not activate PhICl2 as proposed.</div><div><br></div>

Generation and reactivity of an elusive base-stabilised phosphinidene

Reduction of phosphorus dichloride 6, supported by the diaryloxyphenyl group (OCO) featuring two bulky phenoxy wingtips, by PMe3, generates a reactive intermediate that behaves as a base-stabilized phosphinidene (OCO)P (5)....

Conversion of glucose to levulinic acid and upgrade into γ-valerolactone on Ru/TiO2 catalysts

Combining glucose dehydration and the subsequent hydrogenation in one pot is a preferable approach for process development, as such a method allows in situ generation of the reactive intermediate to...

RidA Proteins Protect against Metabolic Damage by Reactive Intermediates

The Rid (YjgF/YER057c/UK114) protein superfamily was first defined by sequence homology with available protein sequences from bacteria, archaea, and eukaryotes (L. Parsons, N. Bonander, E. Eisenstein, M. Gilson, et al., Biochemistry 42:80–89, 2003, https://doi.org/10.1021/bi020541w). The archetypal subfamily, RidA (reactive intermediate deaminase A), is found in all domains of life, with the vast majority of free-living organisms carrying at least one RidA homolog.

Synthesis of Fused Oxepane HIV Integrase Inhibitor MK-1376

Controlling the absolute and relative stereochemistry of a seven-membered oxepane in the formation of HIV integrase inhibitor MK-1376 was accomplished through a strategy involving the use of asymmetric allylation and stereoconvergent, substrate-directed installation of an amine fragment. Surprising reactivity was demonstrated during the asymmetric allylation in which the allyl-pyrimidone product was formed reversibly. The stereoconvergent amine addition was accomplished through an elimination/addition sequence involving a quinone methide reactive intermediate, and nucleophilic trapping of the reactive quinone methide intermediate with methylamine. This novel approach delivered MK-1376, offering 100-fold greater productivity and 50-fold less waste than the initial synthetic chemistry route.