Integration of global ring currents using the Ampere-Maxwell law

Magnetically induced ring currents are calculated from the magnetic shielding tensor by employing the Ampere-Maxwell law. The feasibility of the method is demonstrated by integrating the zz component of the shielding tensor along the symmetry axis of highly symmetric ring-shaped aromatic, antiaromatic and nonaromatic molecules. The calculated ring-current strengths agree perfectly with the ones obtained by integrating the current-density flux passing through a plane cutting half the molecular ring. The method can be used in combination with all electronic structure codes capable of calculating nuclear magnetic resonance (NMR) shielding tensors in general points in space. We also show that nucleus independent chemical shifts (NICS) along the symmetry axis are related to the spatial derivative of the strength of the global ring-current along the z axis.Peer reviewe

Calculating rate constants for intersystem crossing and internal conversion in the Franck-Condon and Herzberg-Teller approximations

Effective and fast algorithms for calculating rate constants for internal conversion (IC) and intersystem crossing (ISC) in the Franck-Condon and Herzberg-Teller approximations have been developed and implemented. The methods have been employed for calculating IC and ISC rate constants for the pyrromethene-567 dye (PM567), hetero[8]circulene (4B) and free-base porphyrin (H2P). The fluorescence quantum yields obtained by comparing calculated rate constants for the radiative and non-radiative processes are in good agreement with experimental data.Peer reviewe

Aromaticity of Even-Number Cyclo[n]carbons (n=6-100)

The recently synthesized cyclo[18]carbon molecule has been characterized in a number of studies by calculating electronic, spectroscopic, and mechanical properties. However, cyclo[18] carbon is only one member of the class of cyclo[n]carbons-standalone carbon allotrope representatives. Many of the larger members of this class of molecules have not been thoroughly investigated. In this work, we calculate the magnetically induced current density of cyclo[n]carbons in order to elucidate how electron delocalization and aromatic properties change with the size of the molecular ring (n), where n is an even number between 6 and 100. We find that the Hiickel rules for aromaticity (4k + 2) and antiaromaticity (4k) become degenerate for large C-n rings (n > 50), which can be understood as a transition from a delocalized electronic structure to a nonaromatic structure with localized current density fluxes in the triple bonds. Actually, the calculations suggest that cyclo[n]carbons with n > 50 are nonaromatic cyclic polyalkynes. The influence of the amount of nonlocal exchange and the asymptotic behavior of the exchange-correlation potential of the employed density functionals on the strength of the magnetically induced ring current and the aromatic character of the large cyclo[n]carbons is also discussed.Peer reviewe

When are Antiaromatic Molecules Paramagnetic?

Magnetizabilities and magnetically induced current densities have been calculated and analyzed for a series of antiaromatic cyclo[4k]carbons (k = 2-11), iso[n]phlorins (n = 4-8), expanded porphyrinoids, and meso-meso, beta-beta,beta-beta triple-linked porphyrin and isophlorin arrays. The cyclo[4k]carbons with k = 2-6 are predicted to be closed-shell paramagnetic molecules due to the very strong paratropic ring current combined with its large radius. Larger cyclo[4k]carbons with k = 6-11 are diamagnetic because they sustain a paratropic ring current whose strength is weaker than -20 nA T-1, which seems to be the lower threshold value for closed-shell paramagnetism. This holds not only for cyclo[4k]carbons but also for other organic molecules like expanded porphyrinoids and oligomers of porphyrinoids. The present study shows that meso-meso, beta-beta, beta-beta triple-linked linear porphyrin and isophlorin arrays have a domainlike distribution of alternating diatropic and paratropic ring currents. The strength of their local paratropic ring currents is weaker than -20 nA T-1 in each domain. Therefore, linear porphyrin and isophlorin arrays become more diamagnetic with increasing length of the ribbon. For the same reason, square-shaped meso-meso, beta-beta, beta-beta triple-linked free-base porphyrin and isophlorin tetramers as well as the Zn(II) complex of the porphyrin tetramer are diamagnetic. We show that closed-shell molecules with large positive magnetizabilities can be designed by following the principle that a strong paratropic current ring combined with a large ring-current radius leads to closed-shell paramagnetism.Peer reviewe

Influence of perhalophenyl groups in the TADF mechanism of diphosphino gold(I) complexes

New perhalophenyl three-coordinated gold(i) complexes using the chelate ligand 1,2-bis(diphenyl-phosphino)benzene (dppBz) and [AuR(tht)] (R = C6F5 (1), o-C6BrF4 (2), p-C6BrF4 (3), o-C6F4I (4), p-C6F4I (5); tht = tetrahydrothiophene) have been prepared. The crystal structures of compounds 1 and 2 consist of distorted three-coordinated Au(i) complexes displaying different Au-P distances at the same gold atom. The complexes show intense photoluminescent emission in the solid state at room temperature (RT) and at 77 K. The study of the dependence of the emission lifetime with temperature suggests the existence of thermally activated delayed fluorescence (TADF) processes at RT. We have computed the rate constants for intersystem crossing and reverse intersystem crossing of the photophysical processes through first-principle calculations, supporting the experimental observations with very good agreement.Peer reviewe

Role of PI3K/AKT/mTOR signaling pathway and sirtuin genes in chronic obstructive pulmonary disease development

Chronic obstructive pulmonary disease (COPD) is a multifactorial disease of the respiratory system which develops as a result of a complex interaction of genetic and environmental factors closely related to lifestyle. We aimed to assess the combined effect of the PI3K/AKT/mTOR signaling pathway (PIK3R1, AKT1, MTOR, PTEN) and sirtuin (SIRT1, SIRT3, SIRT6) genes to COPD risk. SNPs of SIRT1 (rs3758391, rs3818292), SIRT3 (rs3782116, rs536715), SIRT6 (rs107251), AKT1 (rs2494732), PIK3R1 (rs10515070, rs831125, rs3730089), MTOR (rs2295080, rs2536), PTEN (rs701848, rs2735343) genes were genotyped by real-time polymerase chain reaction (PCR) among 1245 case and control samples. Logistic regression was used to detect the association of SNPs in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and smoking pack-years. Significant associations with COPD were identified for SIRT1 (rs3818292) (P = 0.001, OR = 1.51 for AG), SIRT3 (rs3782116) (P = 0.0055, OR = 0.69) and SIRT3 (rs536715) (P = 0.00001, OR = 0.50) under the dominant model, SIRT6 (rs107251) (P = 0.00001, OR = 0.55 for СT), PIK3R1: (rs10515070 (P = 0.0023, OR = 1.47 for AT), rs831125 (P = 0.00001, OR = 2.28 for AG), rs3730089 (P = 0.0007, OR = 1.73 for GG)), PTEN: (rs701848 (P = 0.0015, OR = 1.35 under the log-additive model), and rs2735343 (P = 0.0001, OR = 1.64 for GC)). A significant genotype-dependent variation of lung function parameters was observed for SIRT1 (rs3818292), SIRT3 (rs3782116), PIK3R1 (rs3730089), and MTOR (rs2536). Gene-gene combinations that remained significantly associated with COPD were obtained; the highest risk of COPD was conferred by a combination of G allele of the PIK3R1 (rs831125) gene and GG of SIRT3 (rs536715) (OR = 3.45). The obtained results of polygenic analysis indicate the interaction of genes encoding sirtuins SIRT3, SIRT2, SIRT6 and PI3KR1, PTEN, MTOR and confirm the functional relationship between sirtuins and the PI3K/AKT/mTOR signaling pathway

Polymorphisms in the selectin gene cluster are associated with fertility and survival time in a population of Holstein Friesian cows

Selectins are adhesion molecules, which mediate attachment between leucocytes and endothelium. They aid extravasation of leucocytes from blood into inflamed tissue during the mammary gland’s response to infection. Selectins are also involved in attachment of the conceptus to the endometrium and subsequent placental development. Poor fertility and udder health are major causes for culling dairy cows. The three identified bovine selectin genes SELP, SELL and SELE are located in a gene cluster. SELP is the most polymorphic of these genes. Several SNP in SELP and SELE are associated with human vascular disease, while SELP SNP rs6127 has been associated with recurrent pregnancy loss in women. This study describes the results of a gene association study for SNP in SELP (n = 5), SELL (n = 2) and SELE (n = 1) with fertility, milk production and longevity traits in a population of 337 Holstein Friesian dairy cows. Blood samples for PCR-RFLP were collected at 6 months of age and animals were monitored until either culling or 2,340 days from birth. Three SNP in SELPEx4-6 formed a haplotype block containing a Glu/Ala substitution at rs42312260. This region was associated with poor fertility and reduced survival times. SELPEx8 (rs378218397) coded for a Val475Met variant locus in the linking region between consensus repeats 4 and 5, which may influence glycosylation. The synonymous SNP rs110045112 in SELEEx14 deviated from Hardy Weinberg equilibrium. For both this SNP and rs378218397 there were too few AA homozygotes present in the population and AG heterozygotes had significantly worse fertility than GG homozygotes. Small changes in milk production associated with some SNP could not account for the reduced fertility and only SELPEx6 showed any association with somatic cell count. These results suggest that polymorphisms in SELP and SELE are associated with the likelihood of successful pregnancy, potentially through compromised implantation and placental development

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

ANALYSIS OF THE STRESS CONCENTRATION IN THIN-WALLED ELEMENTS OF STRUCTURES WITH LOCAL IN-DEPTH

One must use a three-dimensional approach to determine the concentration of stresses in thin-walled elements of structures with local deepenings or defects. The stress concentration is analyzed for shells and panels with local deepenings. The authors investigated the effect of the finite element partition of a panel on the results and the concentration of the stress for the pan- els made from the different type of material: the model of Hooke and the model of Neo-Hooke (rubber-like material)