Counterintuitive torsional barriers controlled by hydrogen bonding.

The torsional barriers along the Caryl-Caryl axis of a pair of isosteric disubstituted biphenyls were determined by variable temperature 1H NMR spectroscopy in three solvents with contrasted hydrogen bond accepting abilities (1,1,2,2-tetrachloroethane-d2, nitrobenzene-d5 and dimethyl sulfoxide-d6). One of the biphenyl scaffolds was substituted at its ortho and ortho' positions with N'-acylcarbohydrazide groups that could engage in a pair of intramolecular N-HO=C hydrogen bonding interactions at the ground state, but not at the transition state of the torsional isomerization pathway. The torsional barrier of this biphenyl was exceedingly low despite the presence of the hydrogen bonds (16.1, 15.6 and 13.4 kcal mol-1 in the three aforementioned solvents), compared to the barrier of the reference biphenyl (15.3 ± 0.1 kcal mol-1 on average). Density functional theory and the solvation model developed by Hunter were used to decipher the various forces at play. They highlighted the strong stabilization of hydrogen bond donating solutes not only by hydrogen bond accepting solvents, but also by weakly polar, yet polarizable solvents. As fast exchanges on the NMR time scale were observed above the melting point of dimethyl sulfoxide-d6, a simple but accurate model was also proposed to extrapolate low free activation energies in a pure solvent (dimethyl sulfoxide-d6) from higher ones determined in mixtures of solvents (dimethyl sulfoxide-d6 in nitrobenzene-d5).

A New Subtype of Lichen Planopilaris Affecting Vellus Hairs and Clinically Mimicking Androgenetic Alopecia.

BACKGROUND: Lichen planopilaris (LPP) is a follicular variant of lichen planus. A new subtype of LPP mimicking androgenetic alopecia (AGA) may be misdiagnosed. Inappropriate medical therapy or hair transplantation may exacerbate this subtype. OBJECTIVE: To introduce clinicopathologic findings of a new subtype of LPP that selectively affects vellus hair in the pattern of AGA. MATERIALS AND METHODS: In a cross-sectional study, 433 (66.6%) men and 217 (33.4%) women with alopecia who were candidates of medical treatment or hair transplantation were included. Gross and microscopic attributes of their diseases were investigated. RESULTS: Among the total of 650 patients, 58 (8.9%; 95% confidence interval, 6.7%-11.1%) patients, including 52 women and 6 men, had LPP. We identified a distinct category of LPP presenting with diffuse hair loss in the pattern of AGA with predominant terminal hair, significant decrease in vellus hair, and minute punctuate scars in histopathology. Vellus hair follicles were the main sites of involvement. Perifollicular fibrosis and mild fibrosis with lichenoid lymphocytic infiltration around infundibular area of vellus hair follicles were present. CONCLUSION: There is a new form of LPP with clinical features similar to AGA. This form is histopathologically similar to LPP but selectively affects vellus hair follicles.

Cucurbiturils mimicked by low polarizability solvents with pre-formed cavities: an empirical model to predict hydrocarbon selectivity.

Relative binding affinities of a series of nine rigid hydrocarbons towards the cavity formed by a portion of the inner wall of cucurbit[8]uril (CB[8]) and a positive auxiliary guest were determined by competitive 19F NMR titrations in deuterium oxide. The corresponding free binding energies were corrected by the hydrocarbon computed solvation energies to obtain their free energies of transfer from the gas phase to the CB[8]/auxiliary guest cavity. These energies correlate linearly with the hydrocarbon static polarizabilities, thereby suggesting that the selectivity is driven, perhaps exclusively, by dispersive interactions between the hydrocarbons and the tailor-made cavity, regardless of the degree of unsaturation of the guests. The free energies of transfer also correlate linearly with the energy released upon introduction of the hydrocarbon into a pre-formed cavity extruded from a solvent (benzene) selected to mimic the polarity and polarizability of the CB[8]/auxiliary probe cavity - and this, with a unity slope. Among other features, this empirical model also accurately predicts the relative binding affinities of various rigid hydrocarbons to CB[6] and CB[7], as well as noble gases to CB[5], when the macrocycles are mimicked with pre-formed cavities in perfluorohexane or perfluorohexane/benzene mixtures, both being notoriously non-polar and non-polarizable environments.

Enhanced photoreduction of water catalyzed by a cucurbit[8]uril-secured platinum dimer.

A cucurbit[8]uril (CB[8])-secured platinum terpyridyl chloride dimer was used as a photosensitizer and hydrogen-evolving catalyst for the photoreduction of water. Volumes of produced hydrogen were up to 25 and 6 times larger than those obtained with the corresponding free and cucurbit[7]uril-bound platinum monomer, respectively, at equal Pt concentration. The thermodynamics of the proton-coupled electron transfer from the Pt(ii)-Pt(ii) dimer to the corresponding Pt(ii)-Pt(iii)-H hydride key intermediate, as quantified by density functional theory, suggest that CB[8] secures the Pt(ii)-Pt(ii) dimer in a particularly reactive conformation that promotes hydrogen formation.

Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women.

BACKGROUND: In postmenopausal women with coronary artery disease, conjugated equine estrogen with or without continuous administration of medroxyprogesterone acetate has failed to slow the progression of atherosclerosis. Whether 17beta-estradiol (the endogenous estrogen molecule) alone or administered sequentially with medroxyprogesterone acetate can slow the progression of atherosclerosis is unknown. METHODS: We conducted a double-blind, placebo-controlled trial in 226 postmenopausal women (mean age, 63.5 years) who had at least one coronary-artery lesion. Participants were randomly assigned to usual care (control group), estrogen therapy with micronized 17beta-estradiol alone (estrogen group), or 17beta-estradiol plus sequentially administered medroxyprogesterone acetate (estrogen-progestin group). In all patients the low-density lipoprotein (LDL) cholesterol level was reduced to a target of less than 130 mg per deciliter. The primary outcome was the average per-participant change between base-line and follow-up coronary angiograms in the percent stenosis measured by quantitative coronary angiography. RESULTS: After a median of 3.3 years of follow-up, the mean (+/-SE) change in the percent stenosis in the 169 participants who had a pair of matched angiograms was 1.89+/-0.78 percentage points in the control group, 2.18+/-0.76 in the estrogen group, and 1.24+/-0.80 in the estrogen-progestin group (P=0.66 for the comparison among the three groups). The mean difference in the percent stenosis between the estrogen group and the control group was 0.29 percentage point (95 percent confidence interval, -1.88 to 2.46), and the mean difference between the estrogen-progestin group and the control group was -0.65 (95 percent confidence interval, -2.87 to 1.57). CONCLUSIONS: In older postmenopausal women with established coronary-artery atherosclerosis, 17beta-estradiol either alone or with sequentially administered medroxyprogesterone acetate had no significant effect on the progression of atherosclerosis.

Probing Interactions between Hydrocarbons and Auxiliary Guests inside Cucurbit[8]uril.

The affinities of 20 hydrocarbons for the cavity formed by the inner wall of cucurbit[8]uril and a tolyl unit linked to an auxiliary guest were measured in aqueous solution. Cucurbit[8]uril and the auxiliary guest, a substituted ruthenium tris(2,2'-bipyridyl) complex bearing a trifluoromethyl 19F NMR probe, displayed perfect selectivity toward cyclic hydrocarbons, and cis- and trans-decalin, in particular. Unlike π-π interactions, CH-π interactions, as well as differences in hydrocarbon solvation, contribute significantly to the recognition process.

Quantitative assessment of retrograde ejaculation using semen analysis, comparison with a standardized qualitative questionnaire, and investigating the impact of rhBMP-2.

STUDY DESIGN: This was a prospective study evaluating the incidence of retrograde ejaculation (RE) after anterior lumbar interbody fusion (ALIF) based on laboratory analysis of semen and urine. OBJECTIVE: The purpose of this study was to investigate the incidence of RE based on quantitative semen analysis and to compare the rate with that identified using a standardized qualitative questionnaire administered by telephone. SUMMARY OF BACKGROUND DATA: RE is a specific sexual dysfunction in which semen passes into the bladder during ejaculation. It has long been a known possible complication of ALIF associated with injury to the superior hypogastric plexus occurring during access to the anterior lumbar spine. Although reported in multiple studies, there is no standardized assessment for RE and many studies do not describe the methods by which it was assessed. Recently, there has been increased interest in ALIF-related RE with respect to the use of recombinant human bone morphogenetic protein (rhBMP-2). However, how RE was diagnosed remains loosely defined. One possible assessment of RE is to analyze semen and urine after ejaculation. METHODS: Forty-one male patients undergoing ALIF with posterior pedicle screw instrumentation and fusion at L4-L5 and/or L5-L1 consented to participate in the study. The subjects went to a cryobank for preoperative semen and postejaculatory urine analysis. They returned to the cryobank 3 to 6 months after surgery for repeat testing. The semen analysis consisted of ejaculate volume, total sperm count, concentration, and motility, whereas the urine test reported postejaculatory voided urine for spermatozoa. Postoperatively, patients were called by the principle investigator who conducted an interview based on a standardized questionnaire (completed for 36 patients). Patients were considered to have RE based on the questionnaire if they reported less or no ejaculate fluid. These results were compared with those from the laboratory testing to evaluate the value of the questionnaire in assessing RE. rhBMP-2 was used in 21 of the cases. The incidence of RE was compared in these patients versus those in whom rhBMP-2 was not used. RESULTS: Four patients (9.8%) were diagnosed with RE based on the laboratory analysis, 2 of which resolved spontaneously. Based on the questionnaire, 15 (41.7%) patients reported having RE, including the 4 that were confirmed by laboratory testing. Of the 21 patients treated with rhBMP-2, 2 (9.5%) were diagnosed with RE, 1 of which resolved. Of the 20 patients treated without rhBMP-2, 2 (10.0%) had RE, 1 of which resolved. CONCLUSION: This study suggests that use of a questionnaire tends to overestimate the incidence of RE as compared with the quantitative semen and urine analysis. Contrary to recent studies using retrospective qualitative review, in this small group with quantitative analysis, use of rhBMP-2 was not related to an increased incidence of RE, with a rate of approximately 10% in both patients receiving, and those not receiving, rhBMP-2. Further study of a larger group using preoperative semen and urine analysis, postoperative standard questionnaire and postoperative semen analysis should be pursued to further investigate the occurrence of RE and to possibly assist in developing and validating a questionnaire for RE assessment.