Markovnikov-selective double hydrosilylation of challenging terminal aryl alkynes under cobalt and iron catalysis.

Geminal bis(silanes) are unique compounds with interesting properties. The most straightforward way to access them is double hydrosilylation of alkynes, which was established only recently. Previous articles about transition metal-catalysed double hydrosilylation show that terminal aryl alkynes are a challenge. We report on cobalt(II) and iron(III) complexes with the easy-to-synthesise N,N,N-tridentate hydrazone ligand being active precatalysts in Markovnikov-selective double hydrosilylation of terminal aryl alkynes. The influence of the hydrazone ligand structure and the potential role of the sodium triethylborohydride activator were studied. Sets of geminal bis(silanes) with two identical or different silyl groups were synthesised, showing the applicability of the reported method.

Synthesis and Hemostatic Activity of New Amide Derivatives.

Eight dipeptides containing antifibrinolytic agents (tranexamic acid, aminocaproic acid, 4-(aminomethyl)benzoic acid, and glycine-natural amino acids) were synthesized in a three-step process with good or very good yields. DMT/NMM/TsO- (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate) was used as a coupling reagent. Hemolysis tests were used to study the effects of the dipeptides on blood components. Blood plasma clotting tests were used to examine their effects on thrombin time (TT), prothrombin time (PT), and the activated partial thromboplastin time (aPTT). The level of hemolysis did not exceed 1%. In clotting tests, TT, PT, and aPTT did not differentiate any of the compounds. The prothrombin times for all amides 1-8 were similar. The obtained results in the presence of amides 1-4 and 8 were slightly lower than for the other compounds and the positive control, and they were similar to the results obtained for TA. In the case of amide 3, a significantly decreased aPTT was observed. The aPTTs observed for plasma treated with amide 3 and TA were comparable. In the case of amide 6 and 8, TT values significantly lower than for the other compounds were found. The clot formation and fibrinolysis (CFF) assay was used to assess the influence of the dipeptides on the blood plasma coagulation cascade and the fibrinolytic efficiency of the blood plasma. In the clot formation and fibrinolysis assay, amides 5 and 7 were among the most active compounds. The cytotoxicity and genotoxicity of the synthesized dipeptides were evaluated on the monocyte/macrophage peripheral blood cell line. The dipeptides did not cause hemolysis at any concentrations. They exhibited no significant cytotoxic effect on SC cells and did not induce significant DNA damage.

At Long Last: Olefin Metathesis Macrocyclization at High Concentration.

Macrocyclic lactones, ketones, and ethers can be obtained in the High-Concentration Ring-Closing Metathesis (HC-RCM) reaction in high yield and selectivity at concentrations 40 to 380 times higher than those typically used by organic chemists for similar macrocyclizations. The new method consists of using tailored ruthenium catalysts together with applying vacuum to distill off the macrocyclic product as it is formed by the metathetical backbiting of oligomers. Unlike classical RCM, no large quantities of organic solvents are used, but rather inexpensive nonvolatile diluents, such as natural or synthetic paraffin oils. Moreover, use of a protecting atmosphere or a glovebox is not needed, as the new catalysts are perfectly moisture and air stable. In addition, some other cyclic compounds previously reported as unobtainable by RCM in neat conditions, or in high dilutions even, can be formed with the help of the HC-RCM method.

Axially chiral racemic half-sandwich nickel(ii) complexes by ring-closing metathesis.

A remarkable nickelacycle has been synthesised via olefin metathesis of the α,ω-diene complex [Ni(η5-C5H4R)(Br)(NHC)] (R = C(CH3)2CH2CH[double bond, length as m-dash]CH2, NHC = 1-(6-hexenyl)-3-(2,4,6-trimethylphenyl)-imidazol-2-ylidene). Single-crystal X-ray analysis reveals a helical shape of the molecule and stretching of some interatomic distances in the Ni(ii) coordination sphere. The Cp-NHC tethered complex shows catalytic activity resembling that of the parent complexes.

Anion exchange in [Ni(η(5)-C(5)H(4)R)(Cl)(NHC)]. Counterion effect on the structure and catalytic activity.

A series of novel complexes [Ni(η(5)-C5H4R)(L)(NHC)](+)A(-)2a-2j and [Ni(η(5)-C5H5)(A)(NHC)] 3a-3c has been obtained by anion metathesis from the corresponding chlorides 1a-1d, depending on the anion binding properties and reaction conditions. Solid-state structures of two cationic complexes (2c, 2j) and two complexes with a coordinated anion (3a, 3c) have been determined by X-ray diffraction revealing a trigonal planar geometry in all cases. Unexpectedly, 3c displayed unprecedented for this type of compounds temperature-dependent NMR spectra that were interpreted in terms of spin equilibrium. The cationic complexes 2 were less efficient in styrene polymerization than the parent chlorides 1. However, the activity of 2 and 3 in Suzuki cross-coupling did not depend considerably on the counterion.

Synthesis and evaluation of bifunctional sGC regulators: optimization of a connecting linker.

Hybrid molecules composed of PpIX and cobyrinic acid derivatives conjugated through linkers of varying length and composition were prepared via 1,3-dipolar cycloaddition (CuAAC) or amidation/esteryfication reactions. They were tested for activation of soluble guanylyl cyclase (sGC), a key enzyme in the NO/cGMP signaling pathway, by an in vitro GTP→cGMP conversion assay. Using purified heme-deficient sGC and truncated sGC variants lacking a heme-binding domain, we demonstrated that such hybrid molecules may activate sGC by targeting heme-binding and/or catalytic domain. While all conjugates activated sGC, only selected compounds served as bifunctional regulators and were capable of simultaneous targeting both heme and catalytic domains of sGC. The length and type of a linker connecting both components had a profound effect on the extent of sGC activation, indicating that the linker's type is crucial for their binding affinities with regulatory and catalytic domains. Only hybrids with the conjugated linker of 13-16 atom length synergistically target both domains and displayed the lowest EC50 and highest activating potency. Compounds with shorter connecting linkers were much less potent and were no more active than the cobyrinic acid component alone. The most active conjugate, which showed a 60-fold activation of sGC, was compound 11, in which PpIX and cobyrinic acid components are separated by 11 atoms chain with the triazole moiety in between.