Mikhail Yu. Antipin

Structural simplification of bioactive natural products with multicomponent synthesis. 2. Antiproliferative and antitubulin activities of pyrano[3,2-c]pyridones and pyrano[3,2-c]quinolones

Pyrano[3,2- c]pyridone and pyrano[3,2- c]quinolone structural motifs are commonly found in alkaloids manifesting diverse biological activities. As part of a program aimed at structural simplification of bioactive natural products utilizing multicomponent synthetic processes, we developed compound libraries based on these privileged heterocyclic scaffolds. The selected library members display low nanomolar antiproliferative activity and induce apoptosis in human cancer cell lines. Mechanistic studies reveal that these compounds induce cell cycle arrest in the G2/M phase and block in vitro tubulin polymerization. Because of the successful clinical use of microtubule-targeting agents, these heterocyclic libraries are expected to provide promising new leads in anticancer drug design.

Three-component synthesis and anticancer evaluation of polycyclic indenopyridines lead to the discovery of a novel indenoheterocycle with potent apoptosis inducing properties

A multicomponent reaction of indane-1,3-dione, an aldehyde and an amine-containing aromatic compound leading to the formation of indenopyridine-based heterocyclic medicinal scaffolds has been investigated. It was found that the yields significantly improve when oxygen gas is bubbled through the reaction mixture, facilitating the oxidation of the intermediate dihydropyridine-containing compounds to their aromatic counterparts. Investigation of the reaction scope revealed that formaldehyde, as well as various aliphatic, aromatic and heteroaromatic aldehydes, works well as the aldehyde component. In addition, substituted anilines and diverse aminoheterocycles can be utilized in this process as the amine-containing component. Preliminary biological evaluation of the synthesized library identified a pyrimidine-based polycycle, which rivals the anticancer drug etoposide in its toxicity and apoptosis inducing properties toward a human T-cell leukemia cell line.

“Higher density does not mean higher stability” mystery of paracetamol finally unraveled

Topological analysis of the experimental electron density distribution functions for two polymorphs of paracetamol showed that strong H-bonds are responsible for the higher stability of crystal phase I, weak interactions for the higher density of phase II. This made it possible to finally resolve the contradiction between the relative stabilities and the densities of the two paracetamol polymorphs.

Estimation of Dissociation Energy in Donor−Acceptor Complex AuCl·PPh3 via Topological Analysis of the Experimental Electron Density Distribution Function

The high-resolution X-ray diffraction analysis and plane-wave density functional theory were applied to the investigation of charge density distribution in the donor-acceptor complex of AuCl with PPh3. The approach allows us to estimate the atomic charges, the charge transfer, the energy of weak interactions (Au...H, Au...C, H...Cl, etc.), and Au-P bond energy directly from the experimental data.

The trans influence of F, Cl, Br and I ligands in a series of square-planar Pd(II) complexes. Relative affinities of halide anions for the metal centre in trans-[(Ph3P)2Pd(Ph)X]

Abstract Single crystal X-ray diffraction studies of trans-[(Ph3P)2Pd(Ph)X] (X = F (1), Cl (2), Br (3), and I (4) were carried out. The four structures split in two isostructural and isomorphous groups, namely orthorhombic for 1 and 2 (space group Pbca, Z = 8) and triclinic for 3 and 4 (space group P-1, Z = 2). According to the PdC bond length, the trans influence of X within these pairs follows the trend Cl>F and 1>Br. However, the trans influence of Cl is slightly stronger than that of Br. Both structural and 13C NMR studies revealed that electron-donating effects of (Ph3P)2PdX increase along the series X=I Cl− > Br− > I− is characteristic of halide preference for the Pd complexes. Dissolving 1 and PPN Cl in dry CH2Cl2 resulted in the release of ‘naked’ F− which fluorinated the solvent smoothly to give a mixture of CH2ClF and CH2F2 in high yield. When chloroform was used instead of CH2Cl2, dichlorocarbene was generated slowly, forming the corresponding cyclopropane in the presence of styrene. All observations were rationalized successfully in terms of the filled/filled effect and push/pull interactions.

Remarkable Ligand Effect in Ni- and Pd-Catalyzed Bisthiolation and Bisselenation of Terminal Alkynes: Solving the Problem of Stereoselective Dialkyldichalcogenide Addition to the CC Bond

We have developed two new catalytic systems based on Ni and Pd complexes to solve the challenging problem of dialkyldichalcogenide (Alk2E2; E=S, Se) addition to alkynes. A comparative study of two catalytic systems-Ni/PMe2Ph and Pd/PCy2Ph-has revealed that the Ni catalyst is superior with respect to high catalytic activity and more general scope relative to the Pd system. A novel synthetic methodology was developed for the preparation of (Z)-bis(alkylthio)alkenes and (Z)-bis(alkylseleno)alkenes from terminal alkynes with excellent stereoselectivity and high yields.

Extremely short C–H⋯F contacts in the 1-methyl-3-propyl-imidazolium SiF6—the reason for ionic “liquid” unexpected high melting point

The synthesis and XRD investigation of hexafluorosilicate salt with 1-propyl-3-methyl imidazolium ([Pmim]+) cation is described. Analysis of crystal packing has revealed that an unexpectedly high melting point (mp, 210 °C) of salt resulted from the presence of extremely short interionic C(Im)H⋯F contacts in the crystal (1.94–2.42 A). The absence of strong C–H⋯F interaction for alkyl radicals led to high mobility of substituents and resulted in phase transition of the order–disorder type. The total energy of the CH⋯F interactions in the hypothetical [SiF6(Pmim)6]+4 cluster according to DFT calculation and topological analysis of the electron density distribution attains ca. 33 kcal mol−1.

PALLADIUM(II) COMPLEXES OF HYBRID PHOSPHINE-PHOSPHINE OXIDE LIGANDS

Abstract Complexes of the type [L2PdCl2] , where L = Ph2PCH2P (O) Ph2 (dppmO) , Ph2P (CH2) 2P (O) Ph2 (dppeO) , Ph2P (CH2) 3P (O) Ph2 (dpppO) , Ph2P (CH2) 4P (O) Ph2 (dppbO) , and Ph2PC5H4FeC5H4P (O) Ph2 (dppfcO) , were prepared in high yield from Na2 [PdCl4] and 2 equiv. of the corresponding L in dichloromethane-methanol. All complexes, except for [ (dppfcO) 2PdCl2] , can exist as the cis and trans isomers, or mixtures of both, with the cis⧹trans ratio decreasing in media of low polarity. The ferrocene containing complex, [ (dppfcO) 2PdCl2] , appeared to be exclusively trans in both the solid state and solution, as established by single crystal X-ray diffraction of its 1 : 3 benzene solvate. The ion exchange extraction of dichloromethane solutions of [ (dppmO) 2PdCl2] and [ (dppeO) 2PdCl2] with aqueous NaBF4 furnished the corresponding cationic P,O-chelates, cis- [ (dppmO) 2Pd] 2 (BF−4)2 and cis- [ (dppeO) 2Pd] 2 (BF−4)2. Alternatively, these cations can be generated by the reaction between the chloro complexes, [ (dppmO) 2PdCl2] and [ (dppeO) 2PdCl2] , with Ag+. Single crystal X-ray diffraction of cis- [ (dppeO) 2Pd] 2 (BF−4)2 revealed distinct conformations (a puckered chair and a distorted sofa) for the two chelate rings situated around each Pd atom. A polymeric, poorly soluble material, { [ (dpppO) 2Pd] 2 (BF−4)2}n, was isolated from the reaction between [ (dppO) 2PdCl2] and AgNO3⧹ NaBF4, with both coordinated and free phosphoryl groups being present in the product (IR) . In dilute solutions of the { [ (dpppO) 2Pd] 2 (BF−4)2}n, depolymerization occurred, giving rise to the monomeric cationic chelate, cis- [ (dpppO) 2Pd] 2(BF−4)2.

The formation of a single-bonded (C70−)2 dimer in a new ionic multicomponent complex of cyclotriveratrylene: (Cs+)2(C70−)2·CTV·(DMF)7(C6H6)0.75

The molecular structure and properties of a single-bonded (C70−)2 dimer in a new ionic complex with cyclotriveratrylene (CTV): (Cs+)2·(C70−)2·CTV·(DMF)7·(C6H6)0.75 are presented.

Template synthesis, structure and unusual series of phase transitions in clathrochelate iron(II) α-dioximates and oximehydrazonates formed by capping with functionalized boron-containing agents

Abstract A series of clathrochelate α-dioximates and oximehydrazonates with apical long-chain paraffin and allyl substituents has been synthesized and characterized by X-ray analysis. For the hexadecylboronic FeNx3(BHd)2 complex (where Nx2− is the cyclohexanedion-1,2-dioxime dianion) in the temperature range 100–305 K, two structural phase transitions have been detected by X-ray diffractometry and 57Fe Mossbauer spectroscopy.