In vitro α-glucosidase, docking and density functional theory studies on novel azide metal complexes.

Aim: The goal of this study is to synthesize new metal complexes containing N-methyl-1-(pyridin-2-yl)methanimine and azide ligands as α-glucosidase inhibitors for Type 2 diabetes. Materials & methods: The target complexes (12-16) were synthesized by reacting N-methyl-1-(pyridin-2-yl)methanimine (L1) with sodium azide in the presence of corresponding metal salts. The investigation of target protein interactions, vibrational, electronic and nonlinear optical properties for these complexes was performed by molecular docking and density functional theory studies. Results: Among these complexes, complex 13 (IC50 = 0.2802 ± 0.62 µM) containing Hg ion showed the highest α-glucosidase inhibitory property. On the other hand, significant results were detected for complexes containing Cu and Ag ions. Conclusion: Complex 13 may be an alternate anti-diabetic inhibitor according to in vitro/docking results.

[Box: see text].

Static/dynamic first and second order hyperpolarizabilities, optimized structures, IR, UV-Vis, 1H and 13C NMR spectra for effective charge transfer compounds: A DFT study.

The effective charge transfer compounds, 4-N,N-dimethylamino-4'-N'-methyl-stilbazolium m-trifluoromethylbenzene-sulfonate (DSMFS) and 4-N,N-dimethylamino-4'-N'-methyl-stilbazolium p-trifluoromethylbenzene-sulfonate (DSPFS), were simulated in terms of geometric structure, IR, UV-Vis, 1H NMR and 13C NMR spectra. UV-vis spectra for both molecules give two peaks at 290 and 436 nm assigned as n-π* and π-π* transitions. The HOMO-LUMO energy gap for DSMFS (2.8174 eV) was calculated as lower than that of DSPFS (4.6649 eV). The detailed frontier molecular orbital analysis also indicated that the intra- and inter-molecular charge transfers occur in DSMFS and DSPFS. The static and dynamic (ω = 532 and 1064 nm) nonlinear optical properties were also investigated by using B3LYP/6-311++G(d,p) level. Static first and second order hyperpolarizabilities (ß and γ) of DSMFS were obtained 1.5726 × 10-28 esu and 271.63 × 10-36 esu, and those for DSPFS were obtained as 1.5528 × 10-28 esu and 303.31 × 10-36 esu. The dynamic ß and γ were obtained as higher than the static corresponding parameters. However, the increasing wavelength in dynamic NLO calculations led to a decrease in ß and γ parameters.

First and second order hyperpolarizabilities of flavonol derivatives: A density functional theory study.

In this study, seventeen flavonol derivatives (1-17) were evaluated with regard to their first- and second-order hyperpolarizability parameters. For this purpose, the molecular geometries of 1-17 were optimized by using B3LYP/6-311++G(d,p) level. Spectroscopic characterizations for 1-17 were executed through the calculations of IR, UV-vis, 1H NMR and 13C NMR spectra. The quantum chemical parameters such as electronegativity, chemical hardness, chemical potential and electrophilicity indexes were obtained by using the frontier molecular orbital (FMO) energies. The potential energy distribution (PED) analysis was used to provide a detailed assignment of vibrational bands. Important contributions to electronic absorption bands from FMOs were also evaluated. The distribution of FMOs to the whole molecule was investigated to determine the nature of electronic charge transfers in 1-17. The static and dynamic first- and second-order hyperpolarizability parameters for 1-17 were calculated by using B3LYP/6-311++G(d,p) level. The static ß and γ were calculated at the ranges of 9.8279-0.0303 × 10-29 esu and 80.200-268.40 × 10-36 esu. The dynamic ß and γ (ω = 532 nm) were also obtained in the field of 1.0440-71.786 × 10-29 esu and 306.20-3607.00 × 10-36 esu. This wide range of ß and γ values indicate that flavonol derivatives with rational substitution may be promising candidates for first- and second-order NLO applications.

Concentration effects on optical properties, DFT, crystal characterization and α-glucosidase activity studies: Novel Zn(II) complex.

A novel Zn(II) complex of 6-ClpicH and picH was synthesized and its structure was determined by XRD technique. The detailed experimental optical susceptibility and band gap, refractive index, linear polarizability, optical and electrical conductivity parameters in various concentrations were investigated by means of the UV-Vis spectroscopic data. The optical band gap, refractive index (n), linear optical susceptibility (χ(1)), third-order nonlinear optical susceptibility (χ(3)), second- and third-order nonlinear optical (ß and γ) parameters were examined by using DFT/M06-L and ωB97XD/6-311++G(d,p) levels. The IC50 value of Zn(II) complex against α-glucosidase was also obtained at 0.44 mM. The experimental band gap of the Zn(II) complex at 13, 33, 44 and 94 µM concentrations in ethanol were found to be 4.38, 4.37, 4.35 and 4.28 eV, respectively. The third-order NLO susceptibility χ(3) parameter at 94 µM concentration corresponding to the photon energies of 4.6 and 5.7 eV in the UV-Vis region were observed at 206.6 × 10-13 and 294.3 × 10-13 esu, respectively. Besides, the theoretical χ(3) values were obtained at 50.58 × 10-13 and 20.37 × 10-13 esu by using M06-L level. These results indicate that Zn(II) complex could be an effective third-order NLO candidate material. In brief, the detailed theoretical and experimental structural, spectral and optical properties of the Zn(II) complex were presented comparatively.

Novel metal complexes containing 6-methylpyridine-2-carboxylic acid as potent α-glucosidase inhibitor: synthesis, crystal structures, DFT calculations, and molecular docking.

The World Health Organization (WHO) report shows that diabetes mellitus (DM) will be one of the ten deadly diseases in the near future. The best way to prevent DM is to decrease blood glucose levels and keep under control; therefore, it is important to design and synthesize the effective inhibitors that can be used in the treatment of DM disease. In this respect, a series of ten metal complexes containing 6-methylpyridine-2-carboxylic acid {[Cr(6-mpa)2(H2O)2]·H2O·NO3, (1), [Mn(6-mpa)2(H2O)2], (2), [Ni(6-mpa)2(H2O)2]·2H2O, (3), [Hg(6-mpa)2(H2O)], (4), [Cu(6-mpa)2(Py)], (5), [Cu(6-mpa)2(H2O)]·H2O, (6), [Zn(6-mpa)2(H2O)]·H2O, (7), [Fe(6-mpa)3], (8), [Cd(6-mpa)2(H2O)2]·2H2O, (9), and [Co(6-mpa)2(H2O)2]·2H2O, (10)} were synthesized as α-glucosidase inhibitors. We found that the IC50 values of the synthesized complexes ranged from 0.247 ± 0.10 to > 600 µM against α-glucosidase. The spectral analyses for these complexes characterized by XRD and LC-MS/MS were also carried out by FT-IR and UV-Vis spectra. Additionally, the DFT/HSEh1PBE/6-311G(d,p)/LanL2DZ level was applied to obtain optimal molecular geometries and spectral behaviors as well as significant contributions to the electronic transitions for the complexes. The molecular docking study was also performed to display interactions between the target protein (the template structure Saccharomyces cerevisiae isomaltase) and the synthesized complexes (1-10).

Crystal structure and Hirshfeld surface analysis of (E)-2-(2,4,6-tri-methyl-benzyl-idene)-3,4-di-hydro-naphthalen-1(2H)-one.

A novel chalcone, C20H20O, derived from benzyl-idene-tetra-lone, was synthesized via Claissen-Schmidt condensation between tetra-lone and 2,4,6-tri-methyl-benzaldehyde. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, producing R 2 2(20) and R 2 4(12) ring motifs. In addition, weak C-H⋯π and π-stacking inter-actions are observed. The inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing that the most important contributions for the crystal packing are from H⋯H (66.0%), H⋯C/ C⋯H (22.3%), H⋯O/O⋯H (9.3%), and C⋯C (2.4%) inter-actions. Shape-index plots show π-π stacking inter-actions and the curvedness plots show flat surface patches characteristic of planar stacking.

A novel series of mixed-ligand M(II) complexes containing 2,2'-bipyridyl as potent α-glucosidase inhibitor: synthesis, crystal structure, DFT calculations, and molecular docking.

Diabetes mellitus (DM) is a common degenerative disease and characterized by high blood glucose levels. Since the effective antidiabetic treatments attempt to decrease blood glucose levels, keeping glucose under control is very important. Recent studies have demonstrated that α-glucosidase inhibitor improves postprandial hyperglycemia and then reduces the risk of developing type 2 diabetes in patients. Therefore, the design and synthesis of high affinity glucosidase inhibitors are of great importance. In this regard, novel series of mixed-ligand M(II) complexes containing 2,2'-bipyridyl {[Hg(6-mpa)2(bpy)(OAc)]·2H2O, (1), [Co(6-mpa)2(bpy)2], (2), [Cu(6-mpa)(bpy)(NO3)]·3H2O, (3), [Mn(6-mpa)(bpy)(H2O)2], (4), [Ni(6-mpa)(bpy)(H2O)2]·H2O, (5), [Fe(6-mpa)(bpy)(H2O)2]·2H2O, (6), [Fe(3-mpa)(bpy)(H2O)2]·H2O, (7)} were synthesized as potential α-glucosidase inhibitors. Their effects on α-glucosidase activity were evaluated. All synthesized complexes displayed α-glucosidase inhibitory activity with IC50 values ranging from 0.184 ± 0.015 to > 600 µM. The experimental spectral analyses were carried out using FT-IR and UV-Vis spectroscopic techniques for these complexes characterized by XRD and LC-MS/MS. Moreover, the calculations at density functional theory approximation were used to obtain optimal molecular geometries, vibrational wavenumbers, electronic spectral behaviors, and major contributions to the electronic transitions for the complexes 1-7. Finally, to display interactions between the synthesized complexes and target protein (the template structure Saccharomyces cerevisiae isomaltase), the molecular docking study was carried out.

Crystal structure and Hirshfeld surface analysis of (succinato-κO)[N,N,N',N'-tetra-kis-(2-hy-droxy-eth-yl)ethyl-enedi-amine-κ5 O,N,N',O',O'']nickel(II) tetra-hydrate.

In the title compound, [Ni(C10H24N2O4)(C4H4O4)]·4H2O, the NiII cation is octa-hedrally coordinated by one O atom of the succinate anion and three O atoms and two N atoms from an N,N,N',N'-tetra-kis-(2-hy-droxy-eth-yl)ethyl-enedi-amine mol-ecule. In the crystal, mol-ecules are linked by O-H⋯O and C-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular architecture. Hirshfeld surface analyses and two-dimensional fingerprint plots were used to analyse the inter-molecular inter-actions present in the crystal, indicating that the most important contributions for the crystal packing are from H⋯H (63.3%) and H⋯O/O⋯H (34.5%) inter-actions.

Copper(II) complex with 6-methylpyridine-2-carboxyclic acid: Experimental and computational study on the XRD, FT-IR and UV-Vis spectra, refractive index, band gap and NLO parameters.

Crystal structure of the synthesized copper(II) complex with 6-methylpyridine-2-carboxylic acid, [Cu(6-Mepic)2·H2O]·H2O, was determined by XRD, FT-IR and UV-Vis spectroscopic techniques. Furthermore, the geometry optimization, harmonic vibration frequencies for the Cu(II) complex were carried out by using Density Functional Theory calculations with HSEh1PBE/6-311G(d,p)/LanL2DZ level. Electronic absorption wavelengths were obtained by using TD-DFT/HSEh1PBE/6-311G(d,p)/LanL2DZ level with CPCM model and major contributions were determined via Swizard/Chemissian program. Additionally, the refractive index, linear optical (LO) and non-nonlinear optical (NLO) parameters of the Cu(II) complex were calculated at HSEh1PBE/6-311G(d,p) level. The experimental and computed small energy gap shows the charge transfer in the Cu(II) complex. Finally, the hyperconjugative interactions and intramolecular charge transfer (ICT) were studied by performing of natural bond orbital (NBO) analysis.

The Evaluation of the Clinical Effects of Botulinum Toxin on Nocturnal Bruxism.

OBJECTIVES: Nocturnal bruxism can be managed by botulinum toxin (Botox®) in patients who have not responded to conservative treatment. The aim of this study was to evaluate the efficacy of botulinum toxin A (BTXA) in the treatment of nocturnal bruxism. MATERIAL AND METHODS: The retrospective study comprised 25 female patients, aged 23-55 years (mean 35.84 ± 8.41 years). All patients received a single injection of BTXA in the right and left masseters. Evaluation was made by Visual Analogue Scale (VAS) values, complaint duration, onset of effect, and duration of effectiveness. RESULTS: BTXA produced significant improvements in pain scores. Only 2 adverse events (8%) were recorded. CONCLUSION: BTX-A is effective in the treatment of nocturnal bruxism.

Aldehyde Substituted Phthalocyanines: Synthesis, Characterization and Investigation of Photophysical and Photochemical Properties.

The new free and nickel phthalocyanine derivatives, tetrakis [(2-formylphenoxy)-phthalocyanine (4), tetrakis [(2-formylphenoxy)-phthalocyaninato]nickel(II) (5) have been synthesized via de-protection of tetra acetal-substituted phthalocyanines in acetic acid/FeCl3 system. The starting phthalocyanines, tetrakis [(2-(1,3-dioxolan-2-yl)phenoxy)-phthalocyanine (2) and tetrakis [(2-(1,3-dioxolan-2-yl)phenoxy)-phthalocyaninato]nickel (3), were prepared by the tetramerization of 4-(2-(1,3-dioxolan-2-yl) phenoxy) phthalonitrile (1). The new compounds have been characterized by the combination of FT-IR, (1)H NMR, UV-Vis, Mass spectra and elemental analysis. Compound 1 crystallizes in the Orthorhombic, space group Pbca with a = 9.2542 (4) Å, b = 13.3299 (5) Å, c = 23.2333 (11) Å, and Z = 8. Compound 1 is built up from two planar groups (phthalonitrile and phenoxy), with a dihedral angle of 69.693(36)° between them and non-planar dioxolane group. We report a combined experimental and theoretical study on molecule 1, as well. Geometric, spectroscopic and electronic properties of compound 1 has been calculated using B3LYP method and 6-311++G(dp) basis set. Fluorescence spectroscopy was applied to record the photoluminescence spectra of the prepared phthalocyanines and the photophysical and photochemical properties were examined in DMSO.

Three-Dimensional Volumetric Assessment of the Effect of Decompression on Large Mandibular Odontogenic Cystic Lesions.

PURPOSE: The primary approach to treating large cystic lesions is controversial. The aims of the present study were to assess the effects of decompression before enucleation for the treatment of large cystic lesions and to compare the rate of decrease of keratocystic odontogenic tumor, ameloblastoma, and dentigerous cyst at specific times (preoperatively and at 6 months). PATIENTS AND METHODS: The study included 40 patients (mean age, 31.22 ± 8.78 yr) with large mandibular lesions (>3 cm). Decompression was used to release intraluminal pressure and decrease the volume of the lesion. Three-dimensional computed tomography was applied to all patients at the diagnosis stage and at 6 months after decompression. Volumetric analysis was performed using software designed for 3-dimensional measurement of volumes. Other variables, such as age, gender, and rate of decrease, were recorded. RESULTS: There were important differences in rates of decrease between preoperative and 6-month lesion volumes. Statistical analyses showed no significant differences among groups for age, gender, and histologic lesion type (P > .05). CONCLUSION: Decompression of large cystic lesions could be useful for surgical interventions without complications.

Mandibular bone mineral density in patients with Behçet's disease.

OBJECTIVES: Behçet's disease (BD) is a chronic, recurring vasculitis of unknown etiology. Patients with BD may use a lot of medications associated with the clinical symptoms. Drugs that are used in the treatment of BD may cause bone loss. The aims of the current study were to compare the bone mineral density (BMD) values between BD and healthy volunteers and describe the effect of disease duration on mandibular BMD. MATERIALS AND METHODS: The study comprised 30 healthy volunteers (15 males and 15 females, mean age 35.50±6.80 years) and 45 patients with BD (24 males and 21 females, mean age 38.93±8.93 years). The BD group was subdivided according to disease duration (0-5, 6-10, and >10 years). The BMD value of the mandibular body was determined by the dual energy X-ray absorptiometry technique. RESULTS: The mean mandibular body BMD values were 1.294±0.21 g/cm(2) in the control group and 1.216±0.22 g/cm(2) in the BD patients, although there was no statistically significant difference. The BMD was observed to decrease with increased disease duration but not to a statistically significant degree. CONCLUSION: The results of this study showed that although the BMD value decreased as the duration of the disease increased, no statistically significant difference was found between the BD patients and the healthy control group.

Pentoxifylline and electromagnetic field improved bone fracture healing in rats.

BACKGROUND: The aim of this study was to evaluate the effects of a phosphodiesterase inhibitor pentoxifylline (PTX), electromagnetic fields (EMFs), and a mixture of both materials on bone fracture healing in a rat model. MATERIALS AND METHODS: Eighty male Wistar rats were randomly divided into four groups: Group A, femur fracture model with no treatment; Group B, femur fracture model treated with PTX 50 mg/kg/day intraperitoneal injection; Group C, femur fracture model treated with EMF 1.5±0.2 Mt/50 Hz/6 hours/day; and Group D, femur fracture model treated with PTX 50 mg/kg/day intraperitoneal injection and EMF 1.5±0.2 Mt/50 Hz/6 hours/day. RESULTS: Bone fracture healing was significantly better in Group B and Group C compared to Group A (P<0.05), but Group D did not show better bone fracture healing than Group A (P>0.05). CONCLUSION: It can be concluded that both a specific EMF and PTX had a positive effect on bone fracture healing but when used in combination, may not be beneficial.

Evaluation of calcified carotid atheroma on panoramic radiographs and Doppler ultrasonography in an older population.

AIM: The aim of this study is to determine the reliability of panoramic radiograph (PR) as a screening tool for the detection of calcified carotid atheroma (CCA) by comparing it with Doppler ultrasonography (DU) examination. A second aim was to evaluate the relationship among CCA, systemic diseases, smoking, and body mass index in an older population. MATERIALS AND METHODS: A total of 1,650 PRs of patients aged over 45 years (736 males and 914 females) were randomly selected. All the patients had been referred to the Faculty of Dentistry, Afyon Kocatepe University, Afyonkarahisar, Turkey, during 2013-2014 for routine PR screening. Medical data were collected from the archival records of the dental school. The patients were divided into two groups: Group A (study group), CCA findings were confirmed by DU (n=59); and Group B (control group), CCA findings were not confirmed by DU (n=34). RESULTS: Of the 1,650 individuals, 93 (5.63%) were detected to have CCA on PR. The population consisted of 43 males and 50 females with mean age of 59.84±10.92 years. No difference was determined in respect of CCA between the sexes (P=0.745). There was a significant difference between Group A and Group B in respect of hypertension (P=0.004). But there was no difference between Group A and Group B in respect of age (P=0.495), BMI (P=0.756), diabetes (P=0.168), and smoking (P=0.482) distribution. CONCLUSION: Although PR cannot be used as an initial diagnostic method when searching for CCA, dentists should be aware of CCA on a routine PR, particularly in older patients who may also have the risk factors of obesity, diabetes mellitus, hypertension, and smoking. Recognizing of CCA especially in hypertensive patients could potentially increase the length and quality of life for individuals.

The Synthesis, Characterization, Crystal Structure and Photophysical Properties of a New Meso-BODIPY Substituted Phthalonitrile.

A new highly fluorescent difluoroboradipyrromethene (BODIPY) dye (4) bearing an phthalonitrile group at meso-position of the chromophoric core has been synthesized starting from 4-(4-meso-dipyrromethene-phenoxy)phthalonitrile (3) which was prepared by the oxidation of 4-(2-meso-dipyrromethane-phenoxy)phthalonitrile (2). The structural, electronic and photophysical properties of the prepared dye molecule were investigated. The final product exhibit noticeable spectroscopic properties which were examined by its absorption and fluorescence spectra. The original compounds prepared in the reaction pathway were characterized by the combination of FT-IR, (1)H and (13)C NMR, UV-vis and MS spectral data. It has been calculated; molecular structure, vibrational frequencies, (1)H and (13)C NMR chemical shifts and HOMO and LUMO energies of the title compound by using B3LYP method with 6-311++G(dp) basis set, as well. The final product (4) was obtained as single crystal which crystallized in the triclinic space group P-1 with a = 9.0490 (8) Å, b = 10.5555 (9) Å, c = 11.7650 (9) Å, α = 77.024 (6)°, ß = 74.437 (6)°, γ = 65.211 (6)° and Z = 2. The crystal structure has intermolecular C-H···F weak hydrogen bonds. The singlet oxygen generation ability of the dye (4) was also investigated in different solvents to determine of using in photodynamic therapy (PDT).

The effects of amlodipine and platelet rich plasma on bone healing in rats.

AIM: The aim of this study was to evaluate the effects of calcium channel blocker (CCB) amlodipine (AML), platelet rich plasma (PRP), and a mixture of both materials on bone healing. MATERIALS AND METHODS: Fifty-six male Wistar rats were randomly divided into four groups: group A, tibia defect model with no treatment; group B, tibia defect model treated with AML, 0.04 mg daily by oral gavage; group C, tibia defect model treated with local PRP; group D, tibia defect model treated with local PRP and AML, 0.04 mg daily by oral gavage. RESULTS: At day 21, bone healing was significantly better in groups C and D compared to group A (P<0.05), but comparisons showed no statistically significant difference in group B (P>0.05). At day 30, groups B and C showed no statistically significant difference (P>0.05) compared to group A, but bone healing in group D was significantly better than in group A (P<0.05). Statistically, AML did not affect alkaline phosphatase (ALP) activity at 21 and 30 days (P>0.05), but PRP and AML + PRP increased ALP activity statistically (P<0.05). CONCLUSION: It can be concluded that AML had neither a positive nor a negative effect on bone healing, but when used in combination with PRP, it may be beneficial.

Alterations in maxillary sinus volume among oral and nasal breathers.

BACKGROUND: Oral breathing causes many changes in the facial anatomical structures in adult patients. In this study we aimed to determine the effects of long-term oral breathing (>5 years) on the maxillary sinus volumes among adult male patients. MATERIAL/METHODS: We accessed medical records of 586 patients who had undergone cone beam computed tomography (CBCT) for any reason between September 2013 and April 2014. Patients who had undergone cone-beam dental volumetric tomography scans for any reason and who had answered a questionnaire about breathing were screened retrospectively. Cone beam dental volumetric tomography (I-Cat, Imaging Sciences International, Hatfield, PA, USA) was used to take the images of the maxillo-facial area at a setting of 120 kVp and 3.7 mA. This study involved male patients older than 21 years of age. RESULTS: The study included a total of 239 male patients, of which 68 were oral breathers and 171 were nasal breathers. The mean age of the oral breathers was 48.4 years and that of the nasal breathers was 46.7 years and the difference was not statistically significant (p>0.05). The mean maxillary sinus volumes of the oral and nasal breathers were 9043.49±1987.90 and 10851.77±2769.37, respectively, and the difference in maxillary sinus volume between the 2 groups was statistically significant (p<0.001). CONCLUSIONS: The volume of maxillary sinus in oral breathers (>5 years) was significantly lower than in nasal breathers, but it remains unclear whether this is due to malfunctioning of the nasal cavity or due to the underlying pathological condition.