Benchmark Ab Initio Characterization of the Abstraction and Substitution Pathways of the Cl + CH3CN Reaction

We investigate the reaction pathways of the Cl + CH3CN system: hydrogen abstraction, methyl substitution, hydrogen substitution, and cyanide substitution, leading to HCl + CH2CN, ClCN/CNCl + CH3, ClCH2CN + H, and CH3Cl + CN, respectively. Hydrogen abstraction is exothermic and has a low barrier, whereas the other channels are endothermic with high barriers. The latter two can proceed via a Walden inversion or front-side attack mechanism, and the front-side attack barriers are always higher. The C-side methyl substitution has a lower barrier and also a lower endothermicity than the N-side reaction. The computations utilize an accurate composite ab initio approach and the explicitly correlated CCSD(T)-F12b method. The benchmark classical and vibrationally adiabatic energies of the stationary points are determined with the most accurate CCSD(T)-F12b/aug-cc-pVQZ energies adding further contributions of the post-(T) and core correlation, scalar relativistic effects, spin-orbit coupling, and zero-point energy corrections. These contributions are found to be non-negligible to reach subchemical accuracy.

First record of Neodryinus typhlocybae in Hungary (Hymenoptera: Dryinidae)

Neodryinus typhlocybae (Ashmead, 1893), a Nearctic dryinid wasp species introduced to Europe as a natural enemy of Metcalfa pruinosa (Say, 1830), is first reported here from Hungary. With 3 figures

A szakellátásban megjelenő osteoporosisos nők 10 éves csonttöréskockázata a FRAX^® alapján

Absztrakt Bevezetés: Az osteoporosis-ellátás kulcskérdése a fokozott csonttörési kockázatú betegek azonosítása és kezelése. Célkitűzés: A hazai osteoporosis-szakellátásban megjelenő osteoporosisos nők törési kockázatának felmérése. Módszer: A szerzők keresztmetszeti kérdőíves vizsgálatot végeztek 2009-ben 11 osteoporosis-centrumban ≥50 éves osteoporosisos nőbetegek körében. Felmérték a főbb törési kockázati tényezőket, a FRAX® kalkulátor magyarországi változatával kiszámolták a 10 éves törési kockázatot. Az egészségi állapotot EQ VAS-sal vizsgálták. Eredmények: Az 1301 beteg átlagéletkora 68,5 (SD = 8,3) év, az EQ VAS 62,0 (SD = 17,2) volt, 690 (53%) betegnek volt már törése. A major osteoporosisos törési és a csípőtörési FRAX® átlagosan 20,1 (SD = 13,9), illetve 10,6 (SD = 12,5) volt (10 éves korcsoportonkénti átlagok: 18,5/9,3; 16,2/6,7; 23,0/13,5; 28,9/18,3). A törésen átesettek értékei szignifikánsan magasabbak voltak (p<0,05). Következtetések: Megközelítően azonos a primer és szekunder törésprevenciós kezelésre járó betegek aránya. Az osteoporosis miatt gondozásban részesülők major osteoporoticus törési FRAX®-értéke jelentős többségben magasabb az Egyesült Királyságban minimumként javasolt 7%-nál. A kutatás alapadatokkal szolgál költséghatékonysági elemzésekhez és a magyarországi intervenciós küszöbértékek kialakításához. Orv. Hetil., 2016, 157(4), 146–153

Towards extracellular Ca2+ sensing by MRI: synthesis and calcium-dependent 1H and 17O relaxation studies of two novel bismacrocyclic Gd3+ complexes

Two new bismacrocyclic Gd3+ chelates containing a specific Ca2+ binding site were synthesized as potential MRI contrast agents for the detection of Ca2+ concentration changes at the millimolar level in the extracellular space. In the ligands, the Ca2+-sensitive BAPTA-bisamide central part is separated from the DO3A macrocycles either by an ethylene (L1) or by a propylene (L2) unit [H4BAPTA is 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid; H3DO3A is 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid]. The sensitivity of the Gd3+ complexes towards Ca2+ and Mg2+ was studied by 1H relaxometric titrations. A maximum relaxivity increase of 15 and 10% was observed upon Ca2+ binding to Gd2L1 and Gd2L2, respectively, with a distinct selectivity of Gd2L1 towards Ca2+ compared with Mg2+. For Ca2+ binding, association constants of log K = 1.9 (Gd2L1) and log K = 2.7 (Gd2L2) were determined by relaxometry. Luminescence lifetime measurements and UV–vis spectrophotometry on the corresponding Eu3+ analogues proved that the complexes exist in the form of monohydrated and nonhydrated species; Ca2+ binding in the central part of the ligand induces the formation of the monohydrated state. The increasing hydration number accounts for the relaxivity increase observed on Ca2+ addition. A 1H nuclear magnetic relaxation dispersion and 17O NMR study on Gd2L1 in the absence and in the presence of Ca2+ was performed to assess the microscopic parameters influencing relaxivity. On Ca2+ binding, the water exchange is slightly accelerated, which is likely related to the increased steric demand of the central part leading to a destabilization of the Ln–water binding interaction

Rational Design of α-Helix-Stabilized Exendin-4 Analogues

Exendin-4 (Ex4) is a potent glucagon-like peptide-1 receptor agonist, a drug regulating the plasma glucose level of patients suffering from type 2 diabetes. The molecule’s poor solubility and its readiness to form aggregates increase the likelihood of unwanted side effects. Therefore, we designed Ex4 analogues with improved structural characteristics and better water solubility. Rational design was started from the parent 20-amino acid, well-folded Trp cage (TC) miniprotein and involved the step-by-step N-terminal elongation of the TC head, resulting in the 39-amino acid Ex4 analogue, E19. Helical propensity coupled to tertiary structure compactness was monitored and quantitatively analyzed by electronic circular dichroism and nuclear magnetic resonance (NMR) spectroscopy for the 14 peptides of different lengths. Both 15N relaxation- and diffusion-ordered NMR measurements were established to investigate the inherent mobility and self-association propensity of Ex4 and E19. Our designed E19 molecule has the same tertiary structure as Ex4 but is more helical than Ex4 under all studied conditions; it is less prone to oligomerization and has preserved biological activity. These conditions make E19 a perfect lead compound for further drug discovery. We believe that this structural study improves our understanding of the relationship between local molecular features and global physicochemical properties such as water solubility and could help in the development of more potent Ex4 analogues with improved pharmacokinetic properties

Geomorphology as a Driver of Heavy Metal Accumulation Patterns in a Floodplain

L

Accumulation of Metals in Juvenile Carp (Cyprinus carpio) Exposed to Sublethal Levels of Iron and Manganese: Survival, Body Weight and Tissue

Many oxbows are contaminated by Fe and Mn as a consequence of the elemental concentration of sediment and water originating from the Upper Tisza Region of Hungary. The phenomenon is partly caused by anthropogenic activities and mainly due to the geochemical characteristics of the re- gion. The effects of Fe and Mn on the aquatic ecosystem of these wetlands were investigated in a model experiments in this study. Survival, individual body weight and the elemental concentrations of organs were determined in common carp ( Cyprinus carpio) juveniles reared in Fe and Mn contaminated media (treatment 1: Fe 0.57 mg L − 1 ,Mn0.29mgL − 1 ,treat- ment 2: Fe 0.57 mg L − 1 , Mn 0.625 mg L − 1 , treatment 3: Fe 1.50 mg L − 1 ,Mn0.29mgL − 1 , treatment 4: Fe 1.50 mg L − 1 , Mn 0.625 mg L − 1 and control: Fe 0.005 mg L − 1 ,Mn 0.003 mg L − 1 ), for rearing time of 49 days. The treatment with Fe and Mn did not have any effect on the survival data and individual body weight in the levels tested. The highest con- centration of Fe and Mn was found in the liver and brain of carp juveniles, while the lowest concentration of these ele- ments occurred in the muscular tissue and gills. The treatment where Fe and Mn were applied in the highest concentrations resulted in a statistically higher level of these elements in the brain, grills and muscle tissues. The treatment where only Mn was present in the highest concentration caused increased lev- el of Mn only in the liver. We found metal accumulation in almost every organ; however, the applied concentrations and exposure time did not affect the survival and average body weight of carp juveniles