Does a second halogen atom affect the nature of intermolecular interactions in protic acid-haloethylene complexes? In (E)-1-chloro-2-fluoroethylene-hydrogen chloride it depends on how you look at it

As part of a systematic study of the effect of chlorine substitution on the structures of protic acid haloethylene complexes, the structure of the ({\it E})-1-chloro-2-fluoroethylene-hydrogen chloride complex has been investigated using {\it ab initio} quantum chemistry calculations and microwave spectroscopy. Although theory predicts a non-planar equilibrium structure for this species, it is only 7 cm$^{-1}$ lower in energy than the planar geometry connecting the two equivalent minima on either side of the haloethylene plane, and the observed spectrum is consistent with a planar, average structure, likely the result of zero-point averaging. The geometry is very similar to the fluorine binding, vinyl fluoride-hydrogen chloride complex, suggesting that the substitution of chlorine for a hydrogen {\it trans} to the fluorine atom has very little effect on intermolecular interactions in this case. On the other hand, vinyl chloride-hydrogen chloride adopts a non-planar, chlorine binding configuration so that alternatively one could say that the presence of fluorine has a large effect on protic acid-chlorine interactions

THE MICROWAVE SPECTRUM AND MOLECULAR STRUCTURE OF (E)-1-CHLORO-1,2-DIFLUOROETHYLENE–ACETYLENE

The lowest energy structures for haloethylene-protic acid heterodimers result from an interplay between favorable electrostatic interactions and steric effects. For vinyl fluoride and 1,1-difluoroethylene complexes, steric effects predominate and the resulting planar structure has the acid binding across the double bond (``top''), while for trifluoroethylene, favorable electrostatics forces the complexes to adopt a sterically strained, but still planar structure with the acid at one end of the olefin (``side''). Substitution of a fluorine atom with chlorine allows a relaxation of steric requirements and the side binding motif to chlorine is observed in ({\it Z})-1-chloro-2-fluoroethylene–acetylene despite the presence of the more electronegative fluorine atom. Similarly, in 2-chloro-1,1-difluoroethylene ethylene–acetylene, the acetylene prefers to adopt side binding to chlorine despite having the option of top binding to fluorine. In ({\it E})-1-chloro-1,2-difluoroethylene, the possibilities are switched to top binding to chlorine and side binding to fluorine. Although the side binding arrangement to fluorine is predicted to be lower in energy than top binding to chlorine, a non-planar, crossed geometry, with the centers of the HCCH triple bond and ethylene double bond approximately aligned with each other is predicted as the global minimum when not correcting for basis set superposition error. When the correction is made, the non-planar geometry has an energy higher than both side and top binding. The microwave spectra of four isotopologues of the ({\it E})-1-chloro-1,2-difluoroethylene-HCCH complex reveal that the side binding structure is indeed the one with the lowest energy. This structure is discussed in terms of the balance between electrostatics and sterics

THE MICROWAVE SPECTRUM AND MOLECULAR STRUCTURE OF 1-CHLORO-1-FLUOROETHYLENE–HYDROGEN CHLORIDE

Recent examples of complexes formed between hydrogen chloride and chlorofluoroethylenes have revealed unexpected and surprising structures. To the contrary, the analysis of the microwave rotational spectrum of 1-chloro-1-fluoroethylene-hydrogen chloride shows that it has the ``top binding to fluorine’’ structure typical of earlier dihaloethylene-HCl complexes. However, this result is not predicted by the MP2/6-311++G(2d, 2p) model chemistry on which we had been relying, even when corrected for basis set superposition error. The success of various model chemistries in predicting the experimental result is discussed

TIPPING THE BALANCE BETWEEN ELECTROSTATICS AND STERIC EFFECTS: THE MICROWAVE SPECTRA AND MOLECULAR STRUCTURES OF 2-CHLORO-1,1-DIFLUOROETHYLENE–ACETYLENE AND CIS-1,2-DIFLUOROETHYLENE–ACETYLENE

We have found that the observed average structures of haloethylene-protic acid heterodimers result from an interplay between favorable electrostatic interactions and steric effects. For vinyl fluoride and 1,1-difluoroethylene complexes, steric effects predominate and the acid binds across the double bond (``top''), while for trifluoroethylene, favorable electrostatics forces the complexes to adopt a sterically strained structure with the acid at one end of the olefin (``side''). A relaxation of steric requirements for binding with a chlorine atom leads to different geometries being observed for each of the vinyl chloride complexes with hydrogen fluoride, hydrogen chloride, and acetylene. The side binding motif to chlorine persists in ({\it Z})-1-chloro-2-fluoroethylene–acetylene despite the presence of the more electronegative fluorine atom. For 2-chloro-1,1-difluoroethylene ethylene–acetylene, the acetylene is presented with the option of top binding to fluorine versus side binding to chlorine, whereas with {\it cis}-1,2-difluoroethylene, the only option is side binding to fluorine. The structures of these two complexes are compared to reveal the balance between electrostatics and sterics

MICROWAVE SPECTRUM AND MOLECULAR STRUCTURE OF THE CHIRAL TAGGING CANDIDATE, 3,3-DIFLUORO-1,2-EPOXYPROPANE, AND ITS COMPLEX WITH THE ARGON ATOM

Continuing our efforts in characterizing small molecules for use as potential chiral tags for the conversion of enantiomeric molecules into spectroscopically distinct diasteromeric complexes for chiral analysis, we examine the microwave spectrum and molecular structure of 3,3-difluoro-1,2-epoxypropane. This compound is available as a high vapor pressure liquid, both in enantiomerically pure form and as a racemic mixture, and it is easily incorporated into a free jet expansion for complex formation and spectroscopic analysis. Like the structurally similar 3,3,3-trifluoro-1,2-epoxypropane, it has a simple, hyperfine-free rotational spectrum. This spectrum has been obtained for the most abundant and four singly-substituted isotopologues, all in natural abundance, and the structure of the molecule determined. In addition, the spectrum and structure of the 3,3-difluoro-1,2-epoxypropane-argon complex are obtained

THE IMPORTANCE OF A GOOD FIT: THE MICROWAVE SPECTRA AND MOLECULAR STRUCTURES OF TRANS-1,2-DIFLUOROETHYLENE-HYDROGEN CHLORIDE AND CIS-1,2-DIFLUOROETHYLENE-HYDROGEN CHLORIDE

Previously studied complexes of hydrogen chloride with fluoroethylenes demonstrate that the secondary interaction between the chlorine atom of the HCl and a hydrogen of the ethylene occurs with the sterically accessible {it cis} H-atom in vinyl fluoride rather than the electrostatically favorable geminal hydrogen. However, with 1,1,2-trifluoroethylene the opposite occurs and electrostatics is favored over sterics. The two hydrogen atoms in {it trans}-1,2-difluoroethylene are electrostatically equivalent and each offer the possibility of interacting in a geminal or in a {it cis} fashion. Thus, the observed structure of {it trans}-1,2-difluoroethylene-HCl, with a secondary interaction to the {it cis} H-atom, is consistent with the favorable steric interactions associated with this configuration. On the other hand, in {it cis}-1,2-difluoroethylene only electrostatically-equivalent geminal H-atoms are present. We find that rather than adopting the sterically unfavorable arrangement found in 1,1,2-trifluoroethylene-HCl, the hydrogen chloride in this complex instead forms a bifurcated hydrogen bond with the two F-atoms, and there is no secondary interaction involving the chlorine atom

MICROWAVE SPECTRA AND MOLECULAR STRUCTURES OF ARGON-CIS-1,3,3,3-TETRAFLUORO-1,2-EPOXYPROPANE AND ARGON-OXIRANYLMETHANOL

Connected to our efforts in characterizing substituted oxiranes for use as potential chiral tags for the conversion of enantiomeric molecules into spectroscopically distinct diastereomeric complexes for chiral analysis, we are exploring how argon binding to these species is modulated by varying the identity of the substituents on the epoxy ring. Previously studied systems generally showed close contacts primarily to atoms contained in the ring, but in complexes with cis-1,3,3,3-tetrafluoro-1,2-epoxypropane and oxiranylmethanol, multiple minima of similar energies are predicted by quantum chemistry calculations, including some with significant interactions between the argon atom and substituent atoms. Progress on assigning and analyzing the spectra of these complexes will be reported

EXPLORING THE DETAILS OF INTERMOLECULAR INTERACTIONS VIA A SYSTEMATIC CHARACTERIZATION OF THE STRUCTURES OF THE BIMOLECULAR HETERODIMERS FORMED BETWEEN PROTIC ACIDS AND HALOETHYLENES

In the early 2000’s, the work of Cole and Legon,footnote{G.C. Cole and A.C. Legon, {it Chem. Phys. Lett.} 369, 31-40 (2003).}$^{,}$footnote{G.C. Cole and A.C. Legon, {it Chem. Phys. Lett.} 400, 414-424 (2004).} combined with that done earlier by Kisiel, Fowler, and Legon,footnote{Z. Kisiel, P.W. Fowler, and A.C. Legon, {it J. Chem. Phys.} 93, 3054-3062 (1990).} demonstrated that comparisons among the complexes of HF, HCl, and HCCH each with vinyl fluoride could provide information concerning the strength of intermolecular interactions. Specifically, that the length of the hydrogen bond and its deviation from linearity as a result of a secondary interaction with the nucleophilic portion of the protic acid could be correlated with the hydrogen bond strength. Building on this foundation, we undertook a systematic characterization of the molecular structures of complexes formed between these three acids and the remaining polar fluoroethylenes, seeking to unravel the nature of their intermolecular interactions. What started out as a simple confirmation of chemical intuition regarding relative interaction strengths developed into a fuller appreciation of the competition between electrostatic and steric forces in determining the lowest energy configuration for the heterodimer._x000d_ _x000d_ Additional surprises were in store for us as we expanded the study to chlorofluoroethylenes. Although the first few examples again served to confirm earlier conclusions, subsequent complexes provided unexpected results that signaled an increasing importance of the dispersion interaction in determining the geometry of the complex as well as the fundamental differences in the electron distributions surrounding the halogens in a C--F versus C--Cl bond._x000d_ _x000d_ Our work with these species has not only allowed us to investigate fundamental questions regarding intermolecular interactions, but obtaining and analyzing the spectra of these complexes along with those of the various haloethylene monomers and their complexes with the argon atom have provided an introduction to molecular spectroscopy and structure determination for many undergraduate students

Plasma irisin is elevated in type 2 diabetes and is associated with increased E-selectin levels

BACKGROUND: Irisin is a hormone released mainly from skeletal muscle after exercise which increases adipose tissue energy expenditure. Adipocytes can also release irisin after exercise, acting as a local adipokine to induce white adipose tissue to take on a brown adipose tissue-like phenotype, suggesting that irisin and its receptor may represent a novel molecular target for the treatment of obesity and obesity-related diabetes. Previous reports provide conflicting evidence regarding circulating irisin levels in patients with type 2 diabetes (T2DM). METHODS: This study investigated plasma irisin concentrations in 79 T2DM individuals, assessing potential associations with measures of segmental body composition, markers of endothelial dysfunction and peripheral blood mononuclear cell telomere length (TL). RESULTS: Resting, overnight-fasted plasma irisin levels were significantly higher in this group of T2DM patients compared with levels we previously reported in healthy volunteers (p < 0.001). Moreover, plasma irisin displayed a positive correlation with body mass index (p = 0.04), body fat percentage (p = 0.03), HbA1c (p = 0.03) and soluble E-selectin (p < 0.001). A significant negative association was observed between plasma irisin and visceral adiposity (p = 0.006) in T2DM patients. Multiple regression analysis revealed that circulating soluble E-selectin levels could be predicted by plasma irisin (p = 0.004). Additionally, cultured human umbilical vein endothelial cells (HUVEC) exposed to 200 ng/ml irisin for 4 h showed a significant fourfold increase in E-selectin and 2.5-fold increase in ICAM-1 gene expression (p = 0.001 and p = 0.015 respectively), and there was a 1.8-fold increase in soluble E-selectin in conditioned media (p < 0.05). CONCLUSION: These data suggest that elevated plasma irisin in T2DM is associated with indices of adiposity, and that irisin may be involved in pro-atherogenic endothelial disturbances that accompany obesity and T2DM. Accordingly, irisin may constitute a potentially novel therapeutic opportunity in the field of obesity and cardiovascular diabetology

Measuring quality of life in Duchenne muscular dystrophy : a systematic review of the content and structural validity of commonly used instruments

Duchenne muscular dystrophy (DMD) is an inherited X-linked neuromuscular disorder. A number of questionnaires are available to assess quality of life in DMD, but there are concerns about their validity. This systematic review aimed to appraise critically the content and structural validity of quality of life instruments for DMD. Five databases (EMBASE, MEDLINE, CINAHL, PsycINFO, and Cochrane Library) were searched, with supplementary searches in Google Scholar. We included articles with evidence on the content and/or structural validity of quality of life instruments in DMD, and/or instrument development. Evidence was evaluated against the Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. Fifty five articles featured a questionnaire assessing quality of life in DMD. Forty instruments were extracted and 26 underwent assessment. Forty-one articles contained evidence on content or structural validity (including 37 development papers). Most instruments demonstrated low quality evidence and unsatisfactory or inconsistent validity in DMD, with the majority not featuring direct validation studies in this population. Only KIDSCREEN received an adequate rating for instrument design and a satisfactory result for content validity based on its development, yet, like the majority of PROMs, the measure has not been directly validated for use in DMD. Further research is needed on the validity of quality of life instruments in DMD, including content and structural validity studies in this population