Men Scare Me More: Gender Differences in Social Fear Conditioning in Virtual Reality.

Women nearly twice as often develop social anxiety disorder (SAD) compared to men. The reason for this difference is still being debated. The present study investigates gender differences and the effect of male versus female agents in low (LSA) and high socially anxious (HSA) participants regarding the acquisition and extinction of social fear in virtual reality (VR). In a social fear conditioning (SFC) paradigm, 60 participants actively approached several agents, some of which were paired with an aversive unconditioned stimulus (US) consisting of a verbal rejection and spitting simulated by an aversive air blast (CS+), or without an US (CS-). Primary outcome variables were defined for each of the 4 levels of emotional reactions including experience (fear ratings), psychophysiology (fear-potentiated startle), behavior (avoidance), and cognition (recognition task). Secondary outcome variables were personality traits, contingency ratings, heart rate (HR), and skin conductance response (SCR). As hypothesized, fear ratings for CS+ increased significantly during acquisition and the differentiation between CS+ and CS- vanished during extinction. Additionally, women reported higher fear compared to men. Furthermore, a clear difference in the fear-potentiated startle response between male CS+ and CS- at the end of acquisition indicates successful SFC to male agents in both groups. Concerning behavior, results exhibited successful SFC in both groups and a general larger distance to agents in HSA than LSA participants. Furthermore, HSA women maintained a larger distance to male compared to female agents. No such differences were found for HSA men. Regarding recognition, participants responded with higher sensitivity to agent than object stimuli, suggesting a higher ability to distinguish the target from the distractor for social cues, which were on focus during SFC. Regarding the secondary physiological outcome variables, we detected an activation in HR response during acquisition, but there were no differences between stimuli or groups. Moreover, we observed a gender but no CS+/CS- differences in SCR. SFC was successfully induced and extinguished according to the primary outcome variables. VR is an interesting tool to measure emotional learning processes on different outcome levels with enhanced ecological validity. Future research should further investigate social fear learning mechanisms for developing more efficient treatments of SAD.

Charge transfer via the dative N-B bond and dihydrogen contacts. Experimental and theoretical electron density studies of four deltahedral boranes.

In an approach combining high resolution X-ray diffraction at low temperatures with density functional calculations, two closo-borates, B12H12(2-) (1) and B10H10(2-) (2), and two arachno-boranes, B10H12L2 (L = amine (3) or acetonitrile (4)), are studied by means of Atoms In Molecules (AIM) theory and Electron Localizability Indicator (ELI-D). The charge transfer via the dative N-B bonds in the arachno-boranes and via dihydrogen contacts in the closo-borates is quantified. The dative N-B bond in 4 is significantly shorter and stronger than that in 3 and in small N-B Lewis acid base adducts from the literature. It is even shorter in the gas phase than in the crystal environment in contrast to the bond shortening in the crystal generally found for N-B Lewis acid-base adducts. Furthermore, the calculated charge transfer in terms of AIM charges is opposite to the expected N → B direction but still weak as found for all other N-B bonds. The intramolecular charge redistributions due to intermolecular interactions are quantified by the AIM and ELI-D analysis of contact ion pairs. The latter method gives a deeper understanding of delocalization effects in the borane cages as well as in the counterions. Since dihydrogen bonds are rarely found in crystal structures, one focus was directed to the topologies of the large number of 58 experimentally found contacts of this type. The analysis reveals that the electron density at the bond critical point, the corresponding Laplace function, and the curvature along the bond path (λ3) show a behavior that clearly discriminates these interactions from classical hydrogen bonds, confirming earlier theoretical findings.

Real-space indicators for chemical bonding. Experimental and theoretical electron density studies of four deltahedral boranes.

In an approach combining high-resolution X-ray diffraction at low temperatures with density functional theory calculations, two closo-borates, B(12)H(12)(2-) (1) and B(10)H(10)(2-) (2), and two arachno-boranes, B(10)H(12)L(2) [L = amine (3) or acetonitrile (4)], were analyzed by means of the atoms-in-molecules (AIM) theory and electron localizability indicator (ELI-D). The two-electron three-center (2e3c) bonds of the borane cages are investigated with the focus on real-space indicators for chemical bonding and electron delocalization. In compound 2, only two of the three expected bond critical points (bcp's) are found. However, a weakly populated ELI-D basin is found for this pair of adjacent B atoms and the delocalization index and the Source contributions are on the same order of magnitude as those for the other pairs. The opposite situation is found in the arachno-boranes, where no ELI-D basins are found for two types of B-B pairs, which, in turn, exhibit a bcp. However, again the delocalization index is on the same order of magnitude for this bonding interaction. The results show that an unambiguous real-space criterion for chemical bonding is not given yet for this class of compounds. The arachno-boranes carry a special B-B bond, which is the edge of the crown-shaped molecule. This bond is very long and extremely curved inward the B-B-B ring. Nevertheless, the corresponding bond ellipticity is quite small and the ELI-D value at the attractor position of the disynaptic valence basin is remarkably larger than those for all other B-B valence basins. Furthermore, the value of the ED is large in relation to the B-B bond length, so that only this bond type does not follow a linear relationship of the ED value at the bcp versus B-B bond distances, which is found for all other B-B bcp's. The results indicate that both 2e2c and 2e3c bonding play a distinct role in borane chemistry.

Charge transfer via the dative N-B bond and dihydrogen contacts. Experimental and theoretical electron density studies of small Lewis acid-base adducts.

The electronic characteristics of the dative N−B bond in three Lewis acid−base adducts, hydrazine borane, hydrazine bisborane, and ammonia trifluoroborane, are analyzed by an approach combining experimental electron density determination with a broad variety of theoretical calculations. Special focus is directed to the weak dihydrogen contacts in hydrazine borane. The Atoms In Molecules partitioning scheme is complemented by additional methods like the Source Function, and the Electron Localizability Indicator. For the multipole-free theoretical models of hydrazine borane and hydrazine bisborane, a weak charge donation from Lewis base to acid of about 0.05 e is found, whereas multipole refinement of theoretical and experimental structure factors resulted in opposite signs for the Lewis acid and base fragments. For ammonia trifluoroborane, the donation from Lewis base to acid is slightly larger (about 0.13 e) in the multipole-free models, and the charges obtained by multipole refinement retain the direction of the charge donation but show quite large variations. The natural population analysis charges predict larger charge donations (0.35 e) from the Lewis bases to the acids for the three title complexes. Although the three compounds exhibit intermolecular interactions of different types and strengths, including classical hydrogen bonds, F···H contacts and the already mentioned dihydrogen bonds, almost no charge transfer is detected between different molecules within the crystal environment. The main electronic effect of the formation of the Lewis acid-base adducts and of the crystallization is an increase in the charge separation within the ammonia/hydrazine fragments, which is supported by all investigated bond and atomic properties. The nature of the dative N-B bond is found to be mainly electrostatic, but with a substantial contribution of covalency. The F-B bonds show similarities and differences from the N-B bonds, which makes a distinction of coordinative (or dative) bonds from polar covalent interactions possible.

Transferability and reproducibility in electron-density studies--bond-topological and atomic properties of tripeptides of the type L-alanyl-X-L-alanine.

In the last decade three different data bank approaches have been developed that are intended to make electron-density examinations of large biologically important molecules possible. They rely on Bader's concept of transferability of submolecular fragments with retention of their electronic properties. Therefore, elaborate studies on the quantification of transferability in experiment and theory are still very important. Tripeptides of the type L-alanyl-X-L-alanine (X being any of the 20 naturally encoded amino acids) serve as a model case between amino acids and proteins. The two experimental electron-density determinations (L-alanyl-L-histidinyl-L-alanine and L-alanyl-L-phenylalanyl-L-alanine, highly resolved synchrotron X-ray diffraction data sets) performed in this study and theoretical calculations on all 20 different L-alanyl-X-L-alanine molecules contribute to a better estimation of transferability in the peptide case. As a measure of reproducibility and transferability, standard deviations from averaging over bond-topological and atomic properties of atoms or bonds that are considered equal in their chemical environments were calculated. This way, transferability and reproducibility indices were introduced. It can be shown that experimental transferability indices generally slightly exceed experimental reproducibility indices and that these larger deviations can be attributed to chemical effects such as changes in the geometry (bond lengths and angles), the polarization pattern and the neighboring sphere due to crystal packing. These effects can partly be separated from each other and quantified with the help of gas-phase calculations at optimized and experimental geometries. Thus, the degree of transferability can be quantified in very narrow limits taking into account experimental errors and chemical effects.

On the 2-electron 3-center B-H-B bond: charge density determination of tetraborane(10).

In order to characterize the 2-electron 3-center hydride bridges in arachno-tetraborane, an experimental charge-density study was performed complemented with various theoretical calculations. The charge-density distribution and its topological properties were analyzed according to the "atoms in molecules" theory of Bader. The asymmetric bonding situation of the highly polarized hydride bridges is discussed in detail.

Reproducibility and transferability of topological data: experimental charge density study of two modifications of L-alanyl-L-tyrosyl-L-alanine.

Two crystalline modifications of the tripeptide L-Ala-L-Tyr-L-Ala, which have different solvent molecules in the crystal structure (water and ethanol for modifications 1 and 2), were the subject of experimental charge density studies based on high resolution X-ray data collected at ultra-low temperatures of 9 K (1) and 20 K (2), respectively. The molecular structures and the intermolecular interactions were found to be rather similar in the two crystal lattices, so that this study allowed the reproducibility of the charge density of a given molecule in different (but widely comparable) crystalline environments to be examined. With respect to bond topological and atomic properties, the agreement between the two modifications of the title tripeptide was in the same range as found from the comparison with the previously reported results of tri-L-alanine. It follows that the reproducibility and transferability of quantitative topological data are comparable and that within the accuracy of experimental charge density work the replacement of the central amino acid residue L-Ala by L-Tyr has no significant influence, neither on bond nor on the atomic properties of the oligopeptide main chain. Intermolecular interactions in the form of hydrogen bonds were characterized quantitatively and qualitatively by topological criteria and by mapping the charge density distribution on the Hirshfeld surface.

L-alanylglycyl-L-alanine monohydrate at 20 K.

The X-ray crystal structure of the title compound, C8H15N3O4.H2O, at 20 K (space group P2(1)) reveals that the molecular conformation of the tripeptide is remarkably different from the water-free form (space group P2(1)2(1)2(1)) reported previously [Padiyar & Seshadri (1996), Acta Cryst. C52, 1693-1695].