Sharif Digital Repository

Structure and conformational properties of valsartan were studied by advanced NMR techniques and quantum calculation methods. Potential energy scanning using B3LYP/6-311++g** and B3LYP-D3/6-311++g** methods were performed and four conformers (V1-V4) at minimum points of PES diagram were observed. According to the NMR spectra in acetone-d6, there are two conformers (M and m) with mM = 0.52 ratio simultaneously and energy barriers of the two conformers were predicted from chemical shifts and multiplicities. While, intramolecular hydrogen bond at tetrazole ring and carboxylic groups prevent the free rotation on N6[sbnd]C11 bond in M-conformer, this bond rotates freely in m-conformer. On the... 

Experimental and theoretical conformational study of repaglinide in chloroform and dimethyl sulfoxide was investigated. By applying potential energy scanning (PES) at B3LYP/6-311++g** and B3LYP-D3/6-311++g** level of theory on rotatable single bonds, four stable conformers (R1-R4) were identified. Spin-spin coupling constant values were obtained from a set of 2D NMR spectra (H[sbnd]H COSY, H[sbnd]C HMQC and H[sbnd]C HMBC) and compared to its calculated values. Interestingly, from 1HNMR and 2D-NOESY NMR, it has been found that repaglinide structure is folded in CDCl3 and cause all single bonds to rotate at an extremely slow rate. On the other hand, in DMSO-d6, with strong solvent-solute... 

The structural and conformational behavior of gemcitabine (20; 20-diuoro cytidine) was investigated by advanced NMR experiments and a computational quantum mechanical method (DFT) using Potential Energy Scanning (PES) in gas and solution phases in the Polarizable Continuum Model (PCM). Three stable conformers (G1, G2, and G3) were predicted from minimum points in a potential energy diagram. In order to measure coupling constant values, a set of 2D spectra (H-H COSY, H-C HMQC, and H-C HMBC) was analyzed. Optimized structures and spin-spin coupling constant calculations in gas and solution phases were performed by B3LYP/6-311++G(d,p) method. Both energy and NMR parameters showed that G1-form... 

Background: Focal segmental glomerulosclerosis (FSGS) is considered one of the most severe glomerular diseases and around 80% of cases are resistant to steroid treatment. Since a large proportion of steroid-resistant (SR) FSGS patients progress to end-stage renal disease, other therapeutic strategies may benefit this population. However, identification of non-invasive biomarkers to predict this high-risk population is needed. Objective: We aimed to identify the biomarker candidates to distinguish SR from steroid-sensitive (SS) patients using metabolomics approach and to identify the possible molecular mechanism of resistance. Methods: Urine was collected from biopsy-proven FSGS patients... 

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl-containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The 13C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X-ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible... 

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl-containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The 13C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X-ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible... 

In this study the authors present an in-depth study, analysis and discussion on maximum likelihood (ML)-based receiver for a typical spectrally encoded spread-time CDMA in the presence of multiple narrowband interference (NBI) signals in an additive white Gaussian noise channel. Furthermore, the authors demonstrate that by combining useful properties of ML-based receiver and three-level codes, that is, codes with values of -1, 0, +1, the authors can introduce a new strategy in which superior performance with respect to previous receiver structure based on two-level codes, that is, codes with values of -1, +1, can be attained. With the help of an example, the authors drive, first, the... 

Background: Nonalcoholic fatty liver disease (NAFLD) is the most abundant chronic liver disorder, because racial and ethnic differences may influence prevalence and severity of NAFLD. Objectives: This metabolomic study was conducted to identify the metabolic biomarkers and determine the mechanism of progress of NAFLD in Iranian patients. Methods: Serum samples were collected from 75 participants (37 healthy controls and 38 patients with NAFLD) after an overnight fast. The metabolome of all samples were determined by nuclear magnetic resonance (NMR) and were compared by multivariate statistical analysis. Results: Totally, 19 metabolomic biomarkers were identified by NMR. Compared to healthy... 

Objective(s): The molecular basis of “metabolically healthy obese” and “metabolically unhealthy non-obese” phenotypes is not fully understood. Our objective was to identify metabolite patterns differing in obese (metabolically healthy vs unhealthy (MHO vs MUHO)) and non-obese (metabolically healthy vs unhealthy (MHNO vs MUHNO)) individuals. Materials and Methods: This case-control study was performed on 86 subjects stratified into four groups using anthropometric and clinical measurements: MHO (21), MUHO (21), MHNO (22), and MUHNO (22). Serum metabolites were profiled using nuclear magnetic resonance (NMR). Multivariate analysis was applied to uncover discriminant metabolites, and enrichment... 

Background/Objectives: Curcumin, a natural polyphenol compound in the spice turmeric, has been found to have potent anti-oxidative and anti-inflammatory activity. Curcumin may treat non-alcoholic fatty liver disease (NAFLD) through its beneficial effects on biomarkers of oxidative stress (OS) and inflammation, which are considered as two feature of this disease. However, the effects of curcumin on NAFLD have been remained poorly understood. This investigation evaluated the effects of administrating curcumin on metabolic status in NAFLD patients. Subjects/Methods: Fifty-eight NAFLD patients participated in a randomized, double-blind, placebo-controlled parallel design of study. The subjects... 

Objective(s): Hepatitis B virus infection causes chronic disease such as cirrhosis and hepatocellular carcinoma. The metabolomics investigations have been demonstrated to be related to pathophysiologic mechanisms in many disorders such as hepatitis B infection. The aim of this study was to investigate the saliva metabolic profile of patients with chronic hepatitis B infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Materials and Methods: Saliva from 16 healthy subjects and 20 patients with chronic hepatitis B virus were analyzed by nuclear magnetic resonance (NMR). Then, multivariate statistical analysis was performed to identify... 

In this study, we discuss the postural stability of a nonprehensile manipulation problem, which deals with multibody objects. As a metric for postural stability, we define PRI. Then, the system is posturally stable, if PRI is inside the convex hull of the object-manipulator contact surface. We then discuss that dynamic biped locomotion is a special case of dynamic nonprehensile manipulation in all aspects; we prove that ZMP (zero-moment point) and FRI (zoot rotation indicator) are special cases of PRI (palm rotation indicator). Simulations and experiments corresponding to simple examples support the results