Sexual Functioning and Opioid Maintenance Treatment in Women. Results From a Large Multicentre Study

Opioid maintenance treatment (OMT) is the most widespread therapy for both females and males opioid addicts. While many studies have evaluated the OMT impact on men’s sexuality, the data collected about the change in women’s sexual functioning is still limited despite the fact that it is now well-known that opioids - both endogenous and exogenous - affect the endocrine system and play an important role in sexual functioning. The present study aims to determine how OMT with buprenorphine (BUP) or methadone (MTD) affects sexual health in women; examining also any possible emerging correlation between sexual dysfunction (SD), type of opioid and patients’ mental health. This multi-center study case recruited 258 female volunteers attending Italian public Addiction Outpatients Centers that were stabilized with OMT for at least 3 months. SD was assessed with the Arizona Sexual Experience Scale. The twelve-item General Health Questionnaire was used to assess participants’ mental health conditions. The results show that 56.6% of women receiving OMT for at least 3 months presented SD without significant differences between MTD e BUP groups. The majority of the subjects with SD have a poorer quality of intimate relationships and worse mental health than the average. To the best of our knowledge, the present study is the largest report on the presence of SDs in women as a side effects of MTD and BUP used in OMT. Since SDs cause difficulties in intimate relationships, lower patients’ quality of life and interfere with OMT beneficial outcomes, we recommend that women undertaking an opioid therapy have routine screening for SD and we highlight the importance to better examine opioid-endocrine interactions in future studies in order to provide alternative potential treatments such as the choice of opioid, opioid dose reduction and hormone supplementation

CF3: An overlooked chromophore in VCD spectra. A review of recent applications in structural determination

The VCD spectra of several chiral compounds containing the CF3 group are reviewed and analyzed. The list of compounds contains pharmaceutically relevant molecules as well as simple model molecules, having the value of case studies. In particular we point out the importance of the sign of the VCD band relative to some stretching normal mode of CF3 in the region 1110–1150 cm−1, as diagnostic of the configuration of stereogenic carbons C* to which the CF3 group is bound: the correspondence (−) ↔ (R) and (+) ↔ (S) holds for 100% of 1-aryl-2,2,2-trifluoroethanols. DFT calculations confirm these conclusions, but for the rule established here they serve just as a check. This rule is tested on two new compounds, namely N-tert-butanesulfinyl-1-(quinoline-4-yl)-2,2,2-trifluoroethylamine, 8, and 4-[2-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile, 10, both containing two stereogenic elements, one of them being an asymmetric carbon C* of unknown configuration binding a CF3 group. Discussion of the general validity of the rule is provided and some further tests are run on compounds in well-established drugs

Stereochemistry of 2-(6-fluorophenanthren-1-yl)propionic acid unveiled by enantioselective HPLC, ECD spectroscopy, and TD-DFT calculations

1. Introduction Owing to its peculiarities, fluorine has drawn an increasing attention in the design of new drugs. Among them, fluorinated profens have received particular consideration in reference to the biological activity as successful non-steroidal anti-inflammatory drugs (NSAIDs). In the present communication we report the development of an enantioselective HPLC method for the resolution of racemic 2-(6-fluorophenanthren-1-yl)propionic acid (1),1 and the determination of the absolute configuration (AC) of its enantiomers through electronic circular dichroism (ECD) and time-dependent density functional theory (TD-DFT) computations. 2. Results and Discussion The column (S,S)-Whelk-O\uae1 was efficient for the enantioresolution of profen 1. The single enantiomeric fractions were collected and analyzed for determining their enantiomeric excess and ECD spectra. The AC of the enantiomers of 1 was determined by means of ECD theoretical calculations on (S)-1.2 Molecular mechanics conformational analysis and DFT geometry optimization at the B3LYP/TZ2P level isolated the 4 most populated conformers (a, 53.04%; b, 25.70%; c, 19.81%; d, 1.45%). TD-DFT calculations were performed at the B3LYP/TZ2P level and the theoretical ECD spectrum was determined. The ECD spectrum of the second-eluted enantiomer was found to be in excellent agreement with theoretical calculations on (S)-1; therefore, the AC of the first- and second-eluted enantiomers were assessed as (2R)-1 and (2S)-1, respectively. 3. References [1] Ricci, G., and Ruzziconi, R., J. Org. Chem. 2005, 70, 611-623. [2] Autschbach, J., Chirality 2009, 21, E116-E152

Stereochemical characterization of fluorinated 2-(phenanthren-1-yl)propionic acids by enantioselective high performance liquid chromatography analysis and electronic circular dichroism detection.

Enantioselective high performance liquid chromatography (HPLC) coupled with a detection system based on the simultaneous measurement of UV absorption and electronic circular dichroism (ECD) allows a complete stereochemical characterization of chiral compounds, once the relationship between sign of the chiroptical properties and absolute configuration is determined. In the present communication, the development of enantioselective HPLC methods for the resolution of a series of fluorinated 2-phenanthrenylpropionic acids (1-6) is reported. Different chiral stationary phases (CSPs) were tested: Chiralcel(\uae) OJ, Chiralcel(\uae) OD, Chiralpak(\uae) AD, (S,S)-Whelk-O(\uae) 1, Chirobiotic\u2122 T and α(1)-acid glycoprotein (AGP). The results allow the application of the methods to a reliable determination of the enantiomeric excess for all the examined compounds; the highest enantioselectivity values were obtained with the Hibar(\uae) [(S,S)-Whelk-O(\uae) 1] column for some of the examined compounds. In the case of rac-2-(6-fluorophenanthren-1-yl)propionic acid (1), the relationship between circular dichroism and absolute configuration of the enantiomeric fractions was determined by ECD analysis and time-dependent density functional theory (TD-DFT) calculations. The experimental ECD spectrum of the second-eluted fraction of 1 on the Hibar(\uae) [(S,S)-Whelk-O(\uae) 1] column was found to be in excellent agreement with the theoretical ECD spectrum of (S)-1; therefore, the absolute configuration of the first- and second-eluted enantiomers on the (S,S)-Whelk-O(\uae) 1 CSP was assessed as (R) and (S), respectively, and the elution orders of the enantiomeric forms of 1 were determined on all the different CSPs