Evaluation of log Po/w values of drugs from some molecular structure calculation software

Predictive software packages to estimate the lipophilicity of molecules have become key tools in the new drug design. Six different well-known computational programs including the classical BioByte-clogP and the GALAS algorithm offered by ACDlabs were evaluated through a set of 103 drugs with different structures and functionalities. To evaluate the predictions accuracy, reliable experimental log Po/w values for the whole testing set were carefully selected. The best estimations are performed by GALAS/logP based on the fragmental method, corrected according to the similarity with compounds included in the software training set

A Novel, Extremely Bioavailable Cocrystal of Pterostilbene

New multicomponent solid forms of the nutraceutical pterostilbene have been discovered and characterized through experimental cocrystal screening. Among the coformers tested, picolinic acid formed a cocrystal with a 10-fold enhancement of oral bioavailability in rats, which converts the new cocrystal into a very promising candidate for new formulations of pterostilbene with improved performance

Prediction of the n‑octanol/water partition coefficients in the SAMPL6 blind challenge from MST continuum solvation calculations

The IEFPCM/MST continuum solvation model is used for the blind prediction of n-octanol/water partition of a set of 11 fragment-like small molecules within the SAMPL6 Part II Partition Coefficient Challenge. The partition coefficient of the neutral species (log P) was determined using an extended parametrization of the B3LYP/6-31G(d) version of the Miertus-Scrocco-Tomasi continuum solvation model in n-octanol. Comparison with the experimental data provided for partition coefficients yielded a root-mean square error (rmse) of 0.78 (log P units), which agrees with the accuracy reported for our method (rmse = 0.80) for nitrogen-containing heterocyclic compounds. Out of the 91 sets of log P values submitted by the participants, our submission is within those with an rmse < 1 and among the four best ranked physical methods. The largest errors involve three compounds: two with the largest positive deviations (SM13 and SM08), and one with the largest negative deviations (SM15). Here we report the potentiometric determination of the log P for SM13, leading to a value of 3.62 ± 0.02, which is in better agreement with most empirical predictions than the experimental value reported in SAMPL6. In addition, further inclusion of several conformations for SM08 significantly improved our results. Inclusion of these refinements led to an overall error of 0.51 (log P units), which supports the reliability of the IEFPCM/MST model for predicting the partitioning of neutral compounds

Estratègies d’aula inversa basades en eines web 2.0 per a la millora del procés d’aprenentatge de l’estudiant

Projecte: 2018PID-UB/029Es presenta com a informe final la difusió portada a terme en el marc del projecte d’innovació docent “Estratègies d’aula inversa basades en eines web 2.0 per a la millora del procés d’aprenentatge de l’estudiant” (2018PID-UB/029). El projecte se centra en el desenvolupament i implementació de noves metodologies docents fonamentades en estratègies d’aula inversa basades en eines web 2.0 que potenciïn l’ús i l’aplicació de les TIC en la nostra activitat docent per garantir el correcte seguiment de l’avaluació continuada de l’estudiant i de l’assoliment de les competències de l’assignatura, fomentar la motivació i participació a classe de l’estudiant, a més de facilitar-ne una retroacció activa, àgil i constant, en definitiva, millorar-ne el seu procés d’aprenentatg

Lactate Biosensing for Reliable On-Body Sweat Analysis

Wearable lactate sensors for sweat analysis are highly appealing for both the sports and healthcare fields. Electrochemical biosensing is the approach most widely used for lactate determination, and this technology generally demonstrates a linear range of response far below the expected lactate levels in sweat together with a high influence of pH and temperature. In this work, we present a novel analytical strategy based on the restriction of the lactate flux that reaches the enzyme lactate oxidase, which is immobilized in the biosensor core. This is accomplished by means of an outer plasticized polymeric layer containing the quaternary salt tetradodecylammonium tetrakis(4-chlorophenyl) borate (traditionally known as ETH500). Also, this layer prevents the enzyme from being in direct contact with the sample, and hence, any influence with the pH and temperature is dramatically reduced. An expanded limit of detection in the millimolar range (from 1 to 50 mM) is demonstrated with this new biosensor, in addition to an acceptable response time; appropriate repeatability, reproducibility, and reversibility (variations lower than 5% for the sensitivity); good resiliency; excellent selectivity; low drift; negligible influence of the flow rate; and extraordinary correlation (Pearson coefficient of 0.97) with a standardized method for lactate detection such as ion chromatography (through analysis of 22 sweat samples collected from 6 different subjects performing cycling or running). The developed lactate biosensor is suitable for on-body sweat lactate monitoring via a microfluidic epidermal patch additionally containing pH and temperature sensors. This applicability was demonstrated in three different body locations (forehead, thigh, and back) in a total of five on-body tests while cycling, achieving appropriate performance and validation. Moreover, the epidermal patch for lactate sensing is convenient for the analysis of sweat stimulated by iontophoresis in the subjects’ arm, which is of great potential toward healthcare applications.Farmaci

Insights into the Responding Modes of Highly Potent GadoliniumBased Magnetic Resonance Imaging Probes Sensitive to Zinc Ions

Zn ions (Zn2+) play an important biological role in many diseases; hence, an imaging method for monitoring the Zn2+ distribution in tissues could provide important clinical insights. Recently, we reported a potent Zn-sensitive probe based on the Gd-DO3A (DO3A = 1,4,7,10-tetraazacyclododecane-1,4,7-tricarboxylic acid), modified tyrosine. and di(2-picolyl)amine chelator for this metal cation, which generates an outstanding magnetic resonance imaging (MRI) response. Here we further explored the origin of this unprecedented response and expanded the choice of potential MRI probes by preparing the free acid version of the initial MRI sensor. We report a detailed investigation of the 1H NMR dispersion, 17O NMR, and isothermal titration calorimetry properties of these two MRI probes upon interaction with Zn2+. The performed experiments confirm selective interaction of the MRI probes and target metal cation, which causes substantial changes in the coordination sphere of the paramagnetic center. It also evidenced some aggregation, which enhances the relaxivity response. Interestingly, conversion of the methyl ester to the free carboxylic acid of the tyrosine moiety changes the nature of the aggregates and leads to a smaller relaxivity response. The probes interact with human serum albumin (HSA) in the absence of Zn2+, which leads to a possible modification of the coordination sphere of Gd3+ or a substantial change in the exchange rate of second-sphere water molecules. In the presence of Zn2+, the interaction with HSA is very weak, demonstrating the importance of the Zn2+ coordination sphere in the behavior of these systems