Quadratic susceptibility and first hyperpolarizability of the complex of Cr(CO)(3) with 2.2 paracyclophane

The peculiarities of chemical bonding and nonlinear optical properties of the complex of Cr(CO)(3) with [2.2]paracyclophane (Cr-pCp) have been studied by a combined experimental-theoretical approach. The Cr-pCp complex exhibits second harmonic generation, the efficiency of which was measured by the powder technique at 1064.2 nm fundamental wavelength and estimated theoretically. The comparison of electronic structure of the Cr-pCp with benzene tricarbonyl chromium analogue has revealed an important role of intraligand charge transfer state in pCp moiety conditioned by a strong transannular interaction between aromatic rings which is responsible for the enhanced molecular hyperpolarizability of Cr-pCp

Keto-enol tautomerism and nonlinear optical properties in beta-diketones containing 2.2 paracyclophane

Nonlinear optical properties of [2.2]paracyclophane (pCp) derived beta-diketones containing functional groups with different donor-acceptor properties, bounded to the dicarbonyl fragment, have been studied. Two polymorphic modifications, one of which is characterized by the polar space group Pca2(1) while the other one is centrosymmetric (space group Pbca) were obtained for beta-diketone substituted by thiophene group depending on the crystal growth procedure. All molecules studied exhibit second harmonic generation ability, the efficiency of which was measured by the powder technique at 1064 nm fundamental wavelength. The NLO susceptibility for the compounds studied is analyzed taking into account the structural peculiarities and theoretical calculations

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Competing intramolecular vs. intermolecular hydrogen bonding in phosphoryl-containing secondary alkanols: A structural, spectroscopic and DFT study

Intramolecular hydrogen bonding competes with intermolecular hydrogen bonding in alkanols containing Ph2P(O) group. A character of H-bonding in secondary alkanols Ph2P(O) (CR2)nCH2CH(OH)Me, where n = 0 (1), n = 1, R = H (2), and n = 1, R = Me (3) in crystal state and solutions has been studied by X-ray diffraction, FTIR, and diffusion ordered NMR spectroscopy (DOSY). Quantum chemical calculations and QTAIM analysis of isolated alkanol molecules and their dimers have been performed. In spite of slight difference in the structure of linker between P(O) and OH groups, the studied alcohols in crystal exhibit three types of H-bonds: dimer with intermolecular H-bond, polymeric chains with intermolecular H-bond, and monomer with intramolecular H-bond. Experimental data agree well with structural data of quantum chemical calculations at the M06-2x/6-311G (d,p) level of theory. Energy values (thermodynamic parameters) of DFT-optimized structures for gauche and anti isomers and dimers have been calculated. According to FTIR data in solutions (0.1–0.0001 M), alcohol 1 is the most associated, association of alcohol 2 is much less expressed, while alcohol 3 remains as H-bound monomer. Particle size assessed by DOSY relative to Ph3CH does not change on dilution for alcohols 2 and 3 but varies for alcohol 1. © 2018 Elsevier B.V

A novel family of hepta-coordinated Cr(III) complexes with a planar pentadentate N<inf>3</inf>O<inf>2</inf> Schiff base ligand: synthesis, structure and magnetism

A series of seven-coordinate pentagonal-bipyramidal (PBP) Cr(III) complexes with pentadentate pyridine-based ligands, 2,6-diacetylpyridine bis(4-methoxybenzoylhydrazone), H2DAPMBH (H2LOCH3) or 2,6-diacetylpyridine bis(benzoylhydrazone), H2DAPBH (H2L) and different axial ligands have been prepared. The reaction of the H2LOCH3 with CrCl2·4H2O in methanol or CrCl3·6H2O in CH3CN led to a novel seven-coordinate pentagonal-bipyramidal (PBP) complex [Cr(HLOCH3)Cl2] (1) with the mono-deprotonated chelating ligand in the equatorial plane and two apical Cl atoms. Then, taking advantage of lability of the apical Cl ligands in 1, a number of PBP CrIII complexes with charged (viz. CH3O−, N3−, CN−, NCS−) and neutral (viz. CH3OH, H2O) apical ligands was obtained and characterized: [Cr(HLOCH3)Cl2]·4CHCl3 (1), [Cr(HLOCH3)Cl2]·CH3OH (1a), [Cr(HLOCH3)(H2O)Cl]PF6·CH3OH (2), [Cr(HL)(H2O)Cl]ClO4·0.25H2O (3), [Cr(HLOCH3)(H2O)2](NO3)2·H2O·C2H5OH (4), [Cr(LOCH3)(CH3OH)(OCH3)]·CH3OH (5), [Cr(HLOCH3)(NCS)2]·1.5H2O (6), [Cr(HLOCH3)(N3)2]·xH2O (7, x = 0.2, 8, x = 0, 9, x = 0, three phases in the same synthesis), [Cr(LOCH3)(N3)2][Na(CH3OH)2]·2CH3OH (10), [Cr(LOCH3)(CN)2][Na(H2O)(C2H5OH)] (11). Single crystal X-ray analysis reveals that all the complexes 1–11 have the PBP geometry with a pentadentate ligand in a form of [HLOCH3]− or [LOCH3]2− in the equatorial plane. The PBP complexes are prone to aggregate into dimers or polymers, either due to strong hydrogen bonds or due to the transformation of terminal ligands into bridging between different metallic centers. All complexes 1–11 exhibit considerable in-plane distortion of the CrN3O2 pentagon due to the shift of the CrIII ion from the central position, which is caused by the strong first-order Jahn-Teller (JT) effect for the high-spin 3d3 configuration in the PBP ligand field. The mechanism of JT distortions is rationalized in terms of DFT calculations. DC magnetic measurements indicate a high-spin (S = 3/2) ground state of complex [Cr(HLOCH3)Cl2]·4CHCl3 (1); theoretical analysis of its magnetic properties reveals negative zero-field splitting energy with the anisotropy parameter D = –1.8 cm−1 and weak dimer-like antiferromagnetic spin coupling J = –0.23 cm−1 between neighboring PBP units [CrIII(HLOCH3)Cl2] mediated by π-stacking of planar H2LOCH3 ligands

Binuclearopper(I) borohydrideomplexontaining bridging bis(diphenylphosphino) methane ligands: Polymorphic structuresf [(μ2-dppm)2Cu2(η2-BH4)2] dichloromethane solvate

Bis(diphenylphosphino)methane copper(I) tetrahydroborate wasynthesized by ligandsxchange in bis(triphenylphosphine) copper(I) tetrahydroborate, and characterized by XRD, FTIR, NMR spectroscopy. According to XRD the title compound has dimerictructure, [(μ2-dppm)2Cu2(η2-BH4)2], and crystallizes as CH2Cl2 solvate in two polymorphic forms (orthorhombic, 1, and monoclinic, 2) The details of molecular geometry and the crystal-packing pattern in polymorphs were studied. Theare Twisted Boat-Boat conformation of the core Cu2P4C2 cycle in 1 is found being more stable than Boat-Boat conformation in 2. © 2017 by the authors. Licensee MDPI, Basel, Switzerland

Aryloxy Alkyl Magnesium versus Dialkyl Magnesium in the Lanthanidocene-Catalyzed Coordinative Chain Transfer Polymerization of Ethylene

Complexes [(1,2,4-Ph3C5H2)2NdCl2K(THF)2]2 (Nd1), {[1,2-Ph2-4-(4-MeOC6H4)C5H2]2NdCl2K(THF)2}2 (Nd2), {[1,2-Ph2-4-(2-MeOC6H4)C5H2]2NdCl2[K(THF)4]}(THF)0.5 (Nd3), and [(1,2,4-Ph3C5H2)2TbCl2K]2 (Tb1) have been synthesized, studied by X-ray diffraction analysis, and used in coordinative chain transfer polymerization (CCTP) of ethylene upon activation by alkyl magnesium derivatives. The complexes Nd1 and Tb1 exhibiting similar molecular structures and the same core type have demonstrated similar catalytic activities. Two types of alkylating/chain transfer agents, namely, di-n-butyl magnesium and heteroleptic complex (BHT)Mg(THF)2 nBu Mg1 (BHT = 2,6-di-tert-butyl-4-methylphenoxide), have been studied in this reaction. We have found that (BHT)Mg(PE) products (PE is an oligoethylene chain) are being formed at a relatively high rate while using Mg1 at 40 °C in the solution polymerization of ethylene; the oligomeric products comprise more than 40 ethylene fragments, unlike Mg(PE)2 derivatives, which are obtained from MgnBu2 and contain about 20 ethylene fragments. Luminescence spectroscopy study of the reaction mixtures, while initiating the complex Tb1 by MgnBu2 or Mg1, confirmed the structural proximity and high symmetry of the catalytic complexes for both types of Mg reagents. These experimental results reaffirmed the hypothesis about the CCTP mechanism, suggesting the formation of trinuclear LnMg2 catalytic species. Within this mechanism, we can explain the increase in the polymerization degree (Pn) when Mg1 is used by growing a single oligoethylene chain (PE) per a Mg atom to form (μ-BHT)2Mg2(PE)2 species, whereas application of MgnBu2 provides the growth of two PE chains to form the Mg2(PE)4 product with lower solubility. © 2019 American Chemical Society