Quantum Mechanical Prediction of Dissociation Constants for Thiazol-2-imine Derivatives.

As weak acids or bases, in solution, drug molecules are in either their ionized or nonionized states. A high degree of ionization is essential for good water solubility of a drug molecule and is required for drug-receptor interactions, whereas the nonionized form improves a drug's lipophilicity, allowing the ligand to cross the cell membrane. The penetration of a drug ligand through cell membranes is mainly governed by the pKa of the drug molecule and the membrane environment. In this study, with the aim of predicting the acetonitrile pKa's (pKa(MeCN)) of eight drug-like thiazol-2-imine derivatives, we propose a very accurate and computationally affordable protocol by using several quantum mechanical approaches. Benchmark studies were conducted on a set of training molecules, which were selected from the literature with known pKa(water) and pKa(MeCN). Highly well-correlated pKa values were obtained when the calculations were performed with the isodesmic method at the M062X/6-31G** level of theory in conjunction with SMD solvation model for nitrogen-containing heterocycles. Finally, experimentally unknown pKa(MeCN) values of eight thiazol-2-imine structures, which were previously synthesized by some of us, are proposed.

SAMPL7 blind challenge: quantum-mechanical prediction of partition coefficients and acid dissociation constants for small drug-like molecules.

The physicochemical properties of a drug molecule determine the therapeutic effectiveness of the drug. Thus, the development of fast and accurate theoretical approaches for the prediction of such properties is inevitable. The participation to the SAMPL7 challenge is based on the estimation of logP coefficients and pKa values of small drug-like sulfonamide derivatives. Thereby, quantum mechanical calculations were carried out in order to calculate the free energy of solvation and the transfer energy of 22 drug-like compounds in different environments (water and n-octanol) by employing the SMD solvation model. For logP calculations, we studied eleven different methodologies to calculate the transfer free energies, the lowest RMSE value was obtained for the M06L/def2-TZVP//M06L/def2-SVP level of theory. On the other hand, we employed an isodesmic reaction scheme within the macro pKa framework; this was based on selecting reference molecules similar to the SAMPL7 challenge molecules. Consequently, highly well correlated pKa values were obtained with the M062X/6-311+G(2df,2p)//M052X/6-31+G(d,p) level of theory.

A blind SAMPL6 challenge: insight into the octanol-water partition coefficients of drug-like molecules via a DFT approach.

In this study quantum mechanical methods were used to predict the solvation energies of a series of drug-like molecules both in water and in octanol, in the context of the SAMPL6 n-octanol/water partition coefficient challenge. In pharmaceutical design, n-octanol/water partition coefficient, LogP, describes the drug's hydrophobicity and membrane permeability, thus, a well-established theoretical method that rapidly determines the hydrophobicity of a drug, enables the progress of the drug design. In this study, the solvation free energies were obtained via six different methodologies (B3LYP, M06-2X and ωB97XD functionals with 6-311+G** and 6-31G* basis sets) by taking into account the environment implicitly; the methodology chosen (B3LYP/6-311+G**) was used later to evaluate ΔGsolv by using explicit water as solvent. We optimized each conformer in different solvents separately, our calculations have shown that the stability of the conformers is highly dependent on the solvent environment. We have compared implicitly and explicitly solvated systems, the interaction of one explicit water with drug-molecules at the proper location leads to the prediction of more accurate LogP values.

Oxidative decomposition and mineralization of caffeine by advanced oxidation processes: The effect of hybridization.

The study consists of a detailed investigation of the degradability of the emerging water contaminant-caffeine by homogeneous and heterogeneous Advanced Oxidation Processes (AOP's), estimation of a synergy index for each hybrid operation thereof, and proposing the most plausible reaction mechanisms that are consistent with the experimental data. It also encompasses evaluation of the effect of the water matrix represented by carbonate species and humic acids, as strong scavengers of hydroxyl radicals. The results showed that single AOP's such as sonolysis (577 kHz) and photolysis with H2O2 provided complete caffeine elimination, but they were insufficient for the mineralization of the compound. Hybrid AOP's were considerably more effective, particularly when operated at a heterogeneous mode using commercial TiO2. The most effective hybrid process was UV-H2O2/TiO2, which provided more than 75% TOC decay at the minimum test doses of the reagent and catalyst. While the addition of ultrasound to the process significantly increased the rate of caffeine decomposition, it reduced the overall degradation of the compound to 64% in terms of TOC decay. The antagonistic effect was attributed to the formation of excess H2O2, and the presence of cavity clouds and/or high density layers that inhibited the transmission of UV light. The effect of natural water ingredients was found to reduce the reaction rates, signifying the major contribution of hydroxyl radicals to the destruction of caffeine. The proposed reaction mechanisms based on OH radical attack and the calculated energy barriers were in good agreement with the experimentally detected reaction byproducts.

Hydroxyl radical-mediated degradation of salicylic acid and methyl paraben: an experimental and computational approach to assess the reaction mechanisms.

Advanced oxidation processes (AOPs) using various energy sources and oxidants to produce reactive oxygen species are widely used for the destruction of recalcitrant water contaminants. The current study is about the degradation of two emerging pollutants-salicylic acid (SA) and methyl paraben (MP)-by high-frequency ultrasonication followed by identification of the oxidation byproducts and modeling of the reaction mechanisms using the density functional theory (DFT). The study also encompasses prediction of the aquatic toxicity and potential risk of the identified byproducts to some aquatic organisms bussing the ECOSAR (Ecological Structure Activity Relationships) protocol. It was found that the degradation of both compounds was governed by •OH attack and the pathways consisted of a cascade of reactions. The rate determining steps were decarboxylation (~ 60 kcal mol-1) and bond breakage reactions (~ 80 kcal mol-1), which were triggered by the stability of the reaction byproducts and overcome by the applied reaction conditions. Estimated values of the acute toxicities showed that only few of the byproducts were harmful to aquatic organisms, implying the environmental friendliness of the experimental method.

Incidental bilateral accessory middle cerebral arteries on MR imaging and MR angiography.

Intracranial vascular variations involving the middle cerebral artery are rarely seen. Herein, we report an 11-year-old girl with incidental bilateral accessory middle cerebral arteries, an extremely rare variation, which is the first case in the related literature demonstrated by cranial magnetic resonance imaging and magnetic resonance angiography.

Prevalence of skin disorders among primary school children in Diyarbakir, Turkey.

BACKGROUND: The purpose of this study was to determine the prevalence of childhood dermatoses in Diyarbakir, which is located in the southeastern region of Turkey. MATERIAL AND METHOD: This cross-sectional study was carried out in April 2008 among students of eight randomly selected public primary schools in Diyarbakir. Students were examined and questionnaire was applied to determine socioeconomic levels and socio-demographic features. RESULTS: A total of 1932 students were examined by dermatologists. Nine hundred and fifty three (49.32%) girls, mean age was 11.06±2.13 (range 6-17). The overall point prevalence of skin disorders was 59.1%. Among this sample 776 children (40.2%) had only one skin disease whereas 299 (15.5%) had two and 67 (3.5%) had at least three. The point prevalence of skin disorders was 33.1% among students in grade 1 and 78.9% among students in grade 8 (p<0.05). The most common skin disease was eczema (32.8%), followed by pigmentation disorders (17.2%), skin infections (13.4%), scalp disorders (10.1%) and acne vulgaris (9.6%). Infectious skin problems, pigmentation disorders, hair and scalp disorders and acne vulgaris were more common among girls compared to boys (p<0.05). In addition, infectious skin problems were more common among boarders (p<0.05) compared to day students. CONCLUSION: Skin disorders affected 59.1% of the studied children. Skin disorders were more common among girls and boarders in this study, this group of children should be given specific attention in formulating preventive measures.

Prevalencia de trastornos de la piel en niños que asisten a la escuela primaria en Diyarbakir, Turquía / Prevalence of skin disorders among primary school children in Diyarbakir, Turkey

Antecedentes. El objetivo de este estudio fue determinar la prevalencia de dermatosis pediátricas en Diyarbakir, provincia ubicada en la región sudeste de Turquía. Materiales y métodos. Este fue un estudio transversal realizado en abril de 2008 en alumnos que asistían a ocho escuelas primarias públicas de Diyarbakir seleccionadas al azar. Se examinó a los alumnos y se les administró un cuestionario para determinar el nivel socioeconómico y las características sociodemográficas. Resultados. Los dermatólogos evaluaron, en total, a 1932 alumnos. De ellos, 953 (49,32%) eran niñas, con una media de edad de 11,06 ± 2,13 años (rango: 6-17 años). La prevalencia puntual global de trastornos de la piel fue del 59,1%. En esta muestra, 776 niños (40,2%) tenían solamente una enfermedad de la piel, mientras que 299 (15,5%) tenían dos, y 67 (3,5%), al menos tres. La prevalencia puntual de los trastornos de la piel fue del 33,1% en los alumnos de primer grado y del 78,9% en los alumnos de octavo grado (p < 0,05). Las enfermedades de la piel más frecuentes fueron en primer lugar el eccema (32,8%), seguido de los trastornos de la pigmentación (17,2%), las infecciones cutáneas (13,4%), los trastornos del cuero cabelludo (10,1%) y el acné vulgar (9,6%). Las infecciones cutáneas, los trastornos de la pigmentación, los trastornos del cabello y del cuero cabelludo y el acné vulgar fueron mucho más frecuentes en las niñas que en los varones (p < 0,05). Además, las infecciones cutáneas fueron mucho más habituales en los alumnos pupilos que en los medio pupilos (p < 0,05). Conclusión. Los trastornos de la piel afectaron al 59,1% de los niños estudiados, y se observaron con mayor frecuencia en las niñas y en los pupilos. Es necesario prestar mayor atención a estos grupos a la hora de formular medidas preventivas.

Background. The purpose of this study was to determine the prevalence of childhood dermatoses in Diyarbakir, which is located in the southeastern region of Turkey. Material and Method. This cross-sectional study was carried out in April 2008 among students of eight randomly selected public primary schools in Diyarbakir. Students were examined and questionnaire was applied to determine socioeconomic levels and socio-demographic features. Results. A total of 1932 students were examined by dermatologists. Nine hundred and fifty three (49.32%) girls, mean age was 11.06±2.13 (range 6-17). The overall point prevalence of skin disorders was 59.1%. Among this sample 776 children (40.2%) had only one skin disease whereas 299 (15.5%) had two and 67 (3.5%) had at least three. The point prevalence of skin disorders was 33.1% among students in grade 1 and 78.9% among students in grade 8 (p<0.05). The most common skin disease was eczema (32.8%), followed by pigmentation disorders (17.2%), skin infections (13.4%), scalp disorders (10.1%) and acne vulgaris (9.6%). Infectious skin problems, pigmentation disorders, hair and scalp disorders and acne vulgaris were more common among girls compared to boys (p<0.05). In addition, infectious skin problems were more common among boarders (p<0.05) compared to day students. Conclusion. Skin disorders affected 59.1% of the studied children. Skin disorders were more common among girls and boarders in this study, this group of children should be given specific attention in formulating preventive measures.

Unilateral perirenal fibrosis.

A case of multifocal fibrosclerosis with an extremely unusual unilateral perirenal involvement is reported. Computed tomography and magnetic resonance imaging findings of unilateral perirenal fibrosis are discussed.