Molecular recognition of the HPLC Whelk-O1 selector towards the conformational enantiomers of nevirapine and oxcarbazepine

The presence of stereogenic elements is a common feature in pharmaceutical compounds, and affording optically pure stereoisomers is a frequent issue in drug design. In this context, the study of the chiral molecular recognition mechanism fundamentally supports the understanding and optimization of chromatographic separations with chiral stationary phases. We investigated, with molecular docking, the interactions between the chiral HPLC selector Whelk-O1 and the stereoisomers of two bioactive compounds, the antiviral Nevirapine and the anticonvulsant Oxcarbazepine, both characterized by two stereolabile conformational enantiomers. The presence of fast-exchange enantiomers and the rate of the interconversion process were studied using low temperature enantioselective HPLC and VT-NMR with Whelk-O1 applied as chiral solvating agent. The values of the energetic barriers of interconversion indicate, for the single enantiomers of both compounds, half-lives sufficiently long enough to allow their separation only at critically sub-ambient temperatures. The chiral selector Whelk-O1 performed as a strongly selective discriminating agent both when applied as a chiral stationary phase (CSP) in HPLC and as CSA in NMR spectroscopy

Association between practice of physical activity, educational level and food intake profile of truck drivers

A demanda da sociedade moderna intensificou o trabalho ininterrupto em diversas profissões. Além disso, o modo de organização da sociedade, com atividades predominantemente mecanizadas, tem contribuído para a prevalência de hábitos de vida não saudáveis, como a inatividade física. Este estudo objetiva verificar se fatores ocupacionais, sociodemográficos, antropométricos e alimentares estão associados à prática de atividade física insuficiente e se há diferenças nessa associação entre motoristas de caminhão que trabalham de dia ou à noite. Participaram da pesquisa 470 motoristas de caminhão, que responderam a questionários de dados sociodemográficos, atividade física e frequência alimentar. Foi realizada uma regressão logística univariada para verificar a associação entre atividade física insuficiente e as demais variáveis. Além disso, a regressão logística múltipla foi testada para obter modelos que mostrem a associação de conjuntos de variáveis relacionados à atividade física insuficiente. Os resultados indicaram que a prática de atividade física está associada ao maior nível de escolaridade (OR = 1,84; IC = 1,22-2,76) e menor consumo de bebidas alcoólicas (OR = 1,59; IC = 1,04-2,45). Maior ingestão de cereais integrais (OR = 1,63; IC = 1,08-2,46) foi associada à prática regular de atividade física. Entre os trabalhadores noturnos, foi encontrada associação entre a prática regular de atividade física, maior consumo de cereais integrais (OR = 2,02; IC =1,13-3,60) e menor consumo de carboidratos simples (OR = 1,91; IC = 1,08-3,37).The modern society's demand has intensified uninterrupted work among several professional categories. Besides that, the society's organization, with activities that are predominantly mechanized, has contributed to unhealthy life habits, such as lack of physical activity. The study aims to verify the association of occupational, social-demographic, anthropometric and food intake data with insufficient practice of physical activities and if there are any differences in this association between day and night truck drivers. The 470 truck drivers who participated in this study answered social-demographic, physical activity and food frequency questionnaires. Univariate logistic regression analysis was used to verify the association between insufficient physical activity and the other variables. Additionally, multiple logistic regression was tested to obtain models that show the association between sets of variables related to insufficient physical activity. The results indicated that practice of physical activities is associated with high educational level (OR=1.84; CI = 1.22-2.76) and low alcohol consumption (OR = 1.59; CI = 1.04-2.45). High intake of whole grains (OR = 1.63; CI = 1.08-2.46) was associated with regular practice of physical activity. Among the night workers, we found the association between regular practice of physical activity, high consumption of whole grains (OR = 2.02; CI = 1.13-3.60) and low consumption of simple carbohydrates (OR = 1.91; CI = 1.08-3.37)

Gender sensitivity and stereotypes in medical university students: An Italian cross-sectional study

Gender medicine is crucial to reduce health inequalities. Knowledge about students’ attitudes and beliefs regarding men, women and gender is important to improve gender medicine courses. The aim of this study is to evaluate gender stereotypes and its predictors in Italian medical students. We performed an online cross-sectional study among students from the University of Turin. We used the validated Nijmegen Gender Awareness Scale in Medicine scale to explore gender sensitivity and stereotypes. Multivariable logistic regression model was performed to explore potential predictors of gender awareness. We enrolled 430 students. Female sex, a better knowledge on gender medicine and having had a tutor aware of gender issues are associated with higher gender sensitivity. Older age, a better knowledge on gender medicine and having had a tutor sensitive to gender issues were predictors of more stereotyped opinions towards patients. Having had a tutor aware of gender medicine, male sex and older age were associated with more stereotypes towards doctors. Italian students have high gender sensitivity and low gender stereotypes. Age, higher knowledge of gender medicine and having had a tutor that considered gender were associated with higher gender stereotypes. Focusing on gender awareness in medical schools can contribute to a better care

Chiral Teropyrenes: Synthesis, Structure, and Spectroscopic Studies

: We present the inaugural synthesis of a chiral teropyrene achieved through a four-fold alkyne benzannulation catalyzed by InCl3, resulting in good yields. The product underwent thorough characterization using FT-Raman and FT-IR spectroscopies, demonstrating a close agreement with calculated spectra. X-ray crystallographic analysis unveiled a notable twist in the molecule's backbone, with an end-to-end twist angle of 51°, consistent with computational predictions. Experimentally determined enantiomeric inversion barriers revealed a significant energy barrier of 23 kcal/mol, facilitating the isolation of enantiomers for analysis via circular dichroism (CD) and circularly polarized luminescence (CPL) spectroscopies. These findings mark significant strides in the synthesis and characterization of chiral teropyrenes, offering insights into their structural and spectroscopic properties

Associação entre prática de atividade física, escolaridade e perfil alimentar de motoristas de caminhão

The modern society's demand has intensified uninterrupted work among several professional categories. Besides that, the society's organization, with activities that are predominantly mechanized, has contributed to unhealthy life habits, such as lack of physical activity. The study aims to verify the association of occupational, social-demographic, anthropometric and food intake data with insufficient practice of physical activities and if there are any differences in this association between day and night truck drivers. The 470 truck drivers who participated in this study answered social-demographic, physical activity and food frequency questionnaires. Univariate logistic regression analysis was used to verify the association between insufficient physical activity and the other variables. Additionally, multiple logistic regression was tested to obtain models that show the association between sets of variables related to insufficient physical activity. The results indicated that practice of physical activities is associated with high educational level (OR=1.84; CI = 1.22-2.76) and low alcohol consumption (OR = 1.59; CI = 1.04-2.45). High intake of whole grains (OR = 1.63; CI = 1.08-2.46) was associated with regular practice of physical activity. Among the night workers, we found the association between regular practice of physical activity, high consumption of whole grains (OR = 2.02; CI = 1.13-3.60) and low consumption of simple carbohydrates (OR = 1.91; CI = 1.08-3.37).A demanda da sociedade moderna intensificou o trabalho ininterrupto em diversas profissões. Além disso, o modo de organização da sociedade, com atividades predominantemente mecanizadas, tem contribuído para a prevalência de hábitos de vida não saudáveis, como a inatividade física. Este estudo objetiva verificar se fatores ocupacionais, sociodemográficos, antropométricos e alimentares estão associados à prática de atividade física insuficiente e se há diferenças nessa associação entre motoristas de caminhão que trabalham de dia ou à noite. Participaram da pesquisa 470 motoristas de caminhão, que responderam a questionários de dados sociodemográficos, atividade física e frequência alimentar. Foi realizada uma regressão logística univariada para verificar a associação entre atividade física insuficiente e as demais variáveis. Além disso, a regressão logística múltipla foi testada para obter modelos que mostrem a associação de conjuntos de variáveis relacionados à atividade física insuficiente. Os resultados indicaram que a prática de atividade física está associada ao maior nível de escolaridade (OR = 1,84; IC = 1,22-2,76) e menor consumo de bebidas alcoólicas (OR = 1,59; IC = 1,04-2,45). Maior ingestão de cereais integrais (OR = 1,63; IC = 1,08-2,46) foi associada à prática regular de atividade física. Entre os trabalhadores noturnos, foi encontrada associação entre a prática regular de atividade física, maior consumo de cereais integrais (OR = 2,02; IC =1,13-3,60) e menor consumo de carboidratos simples (OR = 1,91; IC = 1,08-3,37)

Comparison of motor function in patients with Duchenne muscular dystrophy in physical therapy in and out of water: 2-year follow-up

O tratamento para pacientes com Distrofia Muscular de Duchenne (DMD) é multidisciplinar. Fazse necessário entender os efeitos das atividades executadas em solo e imersão para permitir o desenvolvimento de protocolos de intervenção. Objetivo: Comparar a função motora em solo e imersão, no período de 2 anos, em crianças com DMD em acompanhamento fisioterapêutico. Método: Estudo retrospectivo com 23 pacientes diagnosticados DMD, de 8 a 24 anos, assistidos pela Associação Brasileira de Distrofia Muscular (ABDIM). Foram coletados dados da avaliação em imersão (adaptação ao meio líquido, bipedestação, sedestação, rotação transversal, longitudinal, nado e marcha) e em solo (Escalas Egan Klassification e Vignos), no período de dois anos. Resultados: Na análise das avaliações entre os semestres, no período de 2 anos, houve diferença no desempenho das atividades em imersão (p < 0,001) e não foi observada diferença na Escala Egan Klassification (p < 0,003) e na Escala Vignos (p < 0,012). Conclusão: Devido aos princípios físicos da água os pacientes apresentaram manutenção e melhora do escore da avaliação da função motora em imersão. Em contrapartida, foi demonstrada piora dos escores das Escalas Egan Klassification e Vignos que representam a função motora em solo.The treatment for patients with Duchenne Muscular Dystrophy (DMD) is multidisciplinary. It is necessary to understand the effects of activities performed on dry ground as well as waterimmersed to allow the development of intervention protocols. Objective: To compare the motor function of children with DMD in physiotherapy carried out on the ground and immersed over a 2-year period. Method: A retrospective study, assisted by the Brazilian Association of Muscular Dystrophy (ABDIM), of 23 patients diagnosed with DMD, 8-24 years of age. We collected assessment data both water-immersed (adaptation to the water, bipedalism, sitting position, cross and longitudinal rotation, swimming, and running) and on the ground (Egan Klassifikation Scale and Vignos Scale) over a 2-year period. Results: Analyzing the ratings between semesters during the 2-year period, there were differences in the performance of water-immersed activities (p < 0.001) and there was no difference on the Egan Klassifikation Scale (p < 0.003) or the Vignos Scale (p < 0.012). Conclusion: Due to the physical properties of the water, patients either improved or maintained their scores for motor function in water immersion. However, their scores for the Egan Klassifikation and the Vignos scales, which represent motor function on the ground, diminishe

Sterodynamics of chiral and conformationally flexible molecules studied by chromatography and chiro-optical methods

PART A Conformational chirality arises from the presence of stereogenic elements different than the stereogenic centre, as axis, plane and helix. Compounds that exhibit such elements have peculiar characteristics profitably exploited in material chemistry, supramolecular chemistry and asymmetric catalysis. In this work is reported the study of the stereodynamics of helicenes, in the first part, and axially chiral compounds, in the second part, that allowed to determine the energetic barriers of the stereomutation events. Enantioselective HPLC coupled to electronic circular dichroism and optical rotation dispersion has been employed to separate and characterize the enantiomers of the studied compounds gathering valuable information about their outstanding chiroptical properties and interconversion rates. PART B Compounds with a non-planar seven-membered ring in their molecular backbone are known to be chiral. The absence of planarity allows the existence of two enantiomeric species that can interconvert due to a ring-flip mechanism. Many bioactive compounds like benzodiazepines or dibenzoazepinones, widely prescribed for different therapeutic applications, present this structural feature. In this study, is reported the investigation of the stereodynamic behaviour of three different bioactive compounds: the anti-HIV drug Nevirapine and the anti-epileptic Oxcarbazepine, both showing a seven membered ring fused in a tricyclic system, and Estazolam, a triazole-benzodiazepine without a stereogenic centre. Low temperature dynamic-HPLC with chiral stationary phase coupled to computer simulations and NMR studies were employed to demonstrate the presence of two enantiomers in rapid interconversion and to measure the kinetic parameters of the process for all the three investigated compounds. PART C In the first section are reported the results from the period of my academic program at the Ludwig-Maximilians University (LMU) of Munich (GE) under the supervision of Prof. Dr. Oliver Trapp, during the second year of my PhD course. Xaa-Pro bond is a common structural element that can give rise to trans and cis isomers thanks to rotation around the amidic bond. Trans/cis isomerization influences the structure of peptides and proteins resulting as an important feature in controlling signal transduction, aggregation, enzymatic catalysis. This pattern is common in catalytically active small peptides and the trans/cis isomerization can influence the performance of catalysis and the outcome of the reaction. Here is reported the optimization of an analytical method to chromatographically resolve mixtures of conformers trans and cis of proline rich small molecules. The kinetic parameters of the isomerization processes have been measured by variable temperature HPLC experiments coupled to stochastic model-based computations. In the second part it will be discussed the assignment of a chemical correlation and the absolute configuration of four stereoisomers of a conformationally flexible indole derivative featuring a -ketoester fragment and two stereogenic centres. The two diastereoisomeric pairs have syn- and anti-periplanar conformations and can be easily converted into each other by treatment with a base. In this study a combination of different techniques is employed: HPLC, X-ray, ECD, NMR and computational methods. HPLC with ECD detection allowed to chemically correlate the four stereoisomers and the AC is assigned for two of the stereoisomers (one in anti-periplanar conformation and one in syn-periplanar) by X-ray

Molecular Recognition of the HPLC Whelk-O1 Selector towards the Conformational Enantiomers of Nevirapine and Oxcarbazepine

The presence of stereogenic elements is a common feature in pharmaceutical compounds, and affording optically pure stereoisomers is a frequent issue in drug design. In this context, the study of the chiral molecular recognition mechanism fundamentally supports the understanding and optimization of chromatographic separations with chiral stationary phases. We investigated, with molecular docking, the interactions between the chiral HPLC selector Whelk-O1 and the stereoisomers of two bioactive compounds, the antiviral Nevirapine and the anticonvulsant Oxcarbazepine, both characterized by two stereolabile conformational enantiomers. The presence of fast-exchange enantiomers and the rate of the interconversion process were studied using low temperature enantioselective HPLC and VT-NMR with Whelk-O1 applied as chiral solvating agent. The values of the energetic barriers of interconversion indicate, for the single enantiomers of both compounds, half-lives sufficiently long enough to allow their separation only at critically sub-ambient temperatures. The chiral selector Whelk-O1 performed as a strongly selective discriminating agent both when applied as a chiral stationary phase (CSP) in HPLC and as CSA in NMR spectroscopy

Low Temperature Dynamic Chromatography for the Separation of the Interconverting Conformational Enantiomers of the Benzodiazepines Clonazolam, Flubromazolam, Diclazepam and Flurazepam

Benzodiazepines (BZDs) are an important class of psychoactive drugs with hypnotic-sedative, myorelaxant, anxiolytic and anticonvulsant properties due to interaction with the GABAa receptor in the central nervous system of mammals. BZDs are interesting both in clinical and forensic toxicology for their pharmacological characteristics and potential of abuse. The presence of a non-planar diazepine ring generates chiral conformational stereoisomers, even in the absence of stereogenic centers. A conformational enrichment of BZD at the binding sites has been reported in the literature, thus making interesting a stereodynamic screening of a wide range of BZDs. Herein, we report the investigation of three stereolabile 1,4-benzodiazepine included in the class of “designer benzodiazepines” (e.g., diclazepam, a chloro-derivative of diazepam, and two triazolo-benzodiazepines, flubromazolam and clonazolam) and a commercially available BZD known as flurazepam, in order to study the kinetic of the “ring-flip” process that allows two conformational enantiomers to interconvert at high rate at room temperature. A combination of low temperature enantioselective dynamic chromatography on chiral stationary phase and computer simulations of the experimental chromatograms allowed us to measure activation energies of enantiomerization (ΔG‡) lower than 18.5 kcal/mol. The differences between compounds have been correlated to the pattern of substitutions on the 1,4-benzodiazepinic core