Binary Mixtures of Meloxicam and L-Tartaric Acid for Oral Bioavailability Modulation of Pharmaceutical Dosage Forms.

Binary mixtures of active pharmaceutical ingredients (API) are researched to improve the oral bioavailability of pharmaceutical dosage forms. The purpose of this study was to obtain mixtures of meloxicam and L-tartaric acid because tartaric acid improves intestinal absorption and meloxicam is more soluble in a weakly basic environment. The mixtures in the 0-1 molar fraction range, obtained from solvent-assisted mechanosynthesis, were investigated by differential scanning calorimetry (DSC), Fourier Transform Infrared (FTIR) spectroscopy, Fourier Transform Raman spectroscopy (FT-Raman), X-ray powder diffraction (XRD) and solubility tests. The physicochemical characteristics of the compounds obtained from DSC data reveal, for the first time, the formation of a co-crystal at meloxicam molar fraction of 0.5. FTIR spectroscopy data show the existence of hydrogen bonds between the co-crystal components meloxicam and L-tartaric acid. FT-Raman spectroscopy was used complementary with FT-IR spectroscopy to analyze the pure APIs and their mixtures, to emphasize the appearance/disappearance and the shifts of the position/intensity of vibrational bands, following the formation of hydrogen-bonded structures or van der Waals interactions, and to especially monitor the crystal lattice vibrations below 400 cm-1. The experimental results obtained by X-ray powder diffraction confirmed the formation of the co-crystal by the loss and, respectively, the apparition of peaks from the single components in the co-crystal diffractogram. The solubility tests showed that the co-crystal product has a lower aqueous solubility due to the acidic character of the other component, tartaric acid. However, when the solubility tests were performed in buffer solution of pH 7.4, the solubility of meloxicam from the co-crystal mixture was increased by 57% compared to that of pure meloxicam. In conclusion, the studied API mixtures may be considered potential biomaterials for improved drug release molecular solids.

The Influence of Gamma Radiation on Different Gelatin Nanofibers and Gelatins.

Gelatin nanofibers are known as wound-healing biomaterials due to their high biocompatible, biodegradable, and non-antigenic properties compared to synthetic-polymer-fabricated nanofibers. The influence of gamma radiation doses on the structure of gelatin nanofiber dressings compared to gelatin of their origin is little known, although it is very important for the production of stable bioactive products. Different-origin gelatins were extracted from bovine and donkey hides, rabbit skins, and fish scales and used for fabrication of nanofibers through electrospinning of gelatin solutions in acetic acid. Nanofibers with sizes ranging from 73.50 nm to 230.46 nm were successfully prepared, thus showing the potential of different-origin gelatin by-products valorization as a lower-cost alternative to native collagen. The gelatin nanofibers together with their origin gelatins were treated with 10, 20, and 25 kGy gamma radiation doses and investigated for their structural stability through chemiluminescence and FTIR spectroscopy. Chemiluminescence analysis showed a stable behavior of gelatin nanofibers and gelatins up to 200 °C and increased chemiluminescent emission intensities for nanofibers treated with gamma radiation, at temperatures above 200 °C, compared to irradiated gelatins and non-irradiated nanofibers and gelatins. The electron paramagnetic (EPR) signals of DMPO adduct allowed for the identification of long-life HO● radicals only for bovine and donkey gelatin nanofibers treated with a 20 kGy gamma radiation dose. Microbial contamination with aerobic microorganisms, yeasts, filamentous fungi, Staphylococcus aureus, Escherichia coli, and Candida albicans of gelatin nanofibers treated with 10 kGy gamma radiation was under the limits required for pharmaceutical and topic formulations. Minor shifts of FTIR bands were observed at irradiation, indicating the preservation of secondary structure and stable properties of different-origin gelatin nanofibers.

Molecular Modelling of Polychlorinated Dibenzo-p-Dioxins Non-Covalent Interactions with ß and γ-Cyclodextrins.

Polychlorinated dibenzo-p-dioxins (PCDD) are persistent organic pollutants which result as byproducts in industrial or combustion processes and induce toxicity in both wildlife and humans. In this study, all seven PCDD, tetrachlorinated dibenzo-p-dioxins (TCDD), pentachlorinated dibenzo-p-dioxins (P5CDD), hexachlorinated dibenzo-p-dioxins (H6CDD), heptachlorinated dibenzo-p-dioxins (H7CDD), and octachlorinated dibenzo-p-dioxins (OCDD) were studied in interaction with two cyclodextrins, ß-CD and γ-CD, resulting in a total of 40 host-guest complexes. The flexibility of the cyclodextrins was given by the number of glucose units, and the placement of the chlorine groups on the dioxins structure accounted for the different complex formed. Various geometries of interaction obtained by guided docking were studied, and the complexation and binding energy were calculated in the frame of MM+ and OPLS force fields. The results show that the recognition of the PCDD pollutants by the CD may be possible through the formation of PCDD:CD inclusion complexes. This recognition is based on the formation of Coulombic interactions between the chlorine atom of the PCDD and the primary and secondary hydroxyl groups of the CD and van der Waals interaction of the CD hydrophobic cavity with PCDD aromatic structures. Both MM+ and OPLS calculus resulted in close values for the complexation and binding energies. Molecular mechanics calculations offer a proper insight into the molecular recognition process between the PCDD compounds and CD molecules, proved by a good description of the C-H···O bonds formed between the guest and host molecules. It was shown for the first time that CD may efficiently trap PCCDs, opening the way for their tremendous potential use in environmental remediation.

Modification of Cotton and Leather Surfaces Using Cold Atmospheric Pressure Plasma and TiO2-SiO2-Reduced Graphene Oxide Nanopowders.

Surface modification of textile fabrics and leathers is very versatile and allows the products quality improvement. In this work, cotton and leather substrates were pre-treated with cold atmospheric pressure plasma (CAPP) and further coated with TiO2-SiO2-reduced graphene oxide composites in dispersion form. By using a Taguchi scheme, this research evaluated the effect of three significant parameters, i.e., the pre-treatment with CAPP, organic dispersion coating and TiO2-SiO2-reduced graphene oxide (TS/GR) composites, that may affect the morpho-structural properties and photocatalytic activity of modified cotton and leather surfaces. The characteristics of cotton/leather surfaces were evaluated by morphological, structural, optical and self-cleaning ability using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX), X-ray powder diffraction (XRD), attenuated total reflection-Fourier Transform Infrared spectroscopy (ATR-FTIR) and UV-Vis spectroscopy. The self-cleaning performance of the obtained cotton and leather samples was evaluated by photocatalytic discoloration of berry juice surface stains under UV light irradiation for 12 h. The successfulness of coating formulations was proven by the SEM analysis and UV-Vis spectroscopy. The XRD patterns and ATR-FTIR spectra revealed the cellulose and collagen structures as dominant components of cotton and leather substrates. The CAPP treatment did not damage the cotton and leather structures. The photocatalytic results highlighted the potential of TiO2-SiO2-reduced graphene oxide composites in organic dispersion media, as coating formulations, for further use in the fabrication of innovative self-cleaning photocatalytic cotton and leather products.

Physical Chemical Investigation of Gamma-Irradiated Parchment for Preservation of Cultural Heritage.

The historical artefacts of parchment are prone to degradation if the storage conditions are improper due to the collagen structure having a limited stability under physical, chemical, and biological agent attacks. The parchment structure is difficult to characterize due to the variety of manufacturing traditions (eastern/western), intrinsic variability of skins (i.e., species, breeding variation, living conditions, effects of pathologies, etc.), biodeterioration, and aging, and the main concern in its analysis is its uniformity. The deterioration of parchment collagen produces a rather stiff or in some circumstances, a relaxed structure. Any intervention or treatment of unique, very precious cultural heritage artefacts must not negatively influence the properties of the component materials. Gamma irradiation is a relatively new technique of bioremediation. Data on the leather properties pre- and post-ionizing radiation bioremediation treatments are few in the literature. Fewer data are available on the historical leather and parchment physical chemical characteristics after ionizing gamma irradiation. This research had two main objectives: (i) the characterization of the parchment structure's uniformity across the analyzed areas and its mechanical properties, i.e., tensile stress by mechanical tests and ATR-FTIR spectroscopy; and (ii) to establish parchment tolerance when exposed to ionizing gamma radiation as a pre-requisite for cultural heritage preservation irradiation treatment. It was found that the mechanical tests and ATR-FTIR spectroscopy may identify changes in the parchment's irradiated structure and that the preservation of cultural heritage parchment artefacts may be performed at maximum 15 kGy gamma irradiation dose.

Outcomes and Economic Evaluation in Delayed Two-Stage Breast Reconstruction in Romania: The Influence of Radiotherapy.

The current paper is a retrospective cohort study conducted on sixty-seven patients who underwent two-stage breast reconstruction over a 5-year period (2015-2020). Forty-one (61.2%) patients received radiotherapy (RT group), and twenty-six (38.8%) did not (non-RT group). Data regarding patients, oncological therapies, type of reconstruction, time of hospitalization, complications, and costs were collected. The statistical analysis was performed using IBM SPSS Statistics 25. General complications were noted for 18 patients (43.9%) in the RT group and for 7 patients (26.9%) in the non-RT group. Major complications were observed only in the first group (five patients-12.2%). The mean time of hospitalization in the RT group was 14.83 days for patients with complications versus 9.83 days for those without complications and 15.5 days versus 8.63 days, respectively, in the non-RT group. The mean cost for patients without complications was 235.64 euros, whereas the cost for patients with complications was 330.24 euros (p = 0.001). Radiation therapy can affect the overall outcome by increasing the risk of complications and increasing costs; however, our paper shows that the association of alloplastic reconstruction in patients with radiotherapy can be performed safely and with low costs in carefully selected patients.

Innovative Protein Gel Treatments to Improve the Quality of Tomato Fruit.

This study aims to establish the effect of biostimulatory protein gels on the quality of tomato. One of the most consumed vegetables, tomato (Lycopersicon esculentum Mill.) is a rich source of healthy constituents. Two variants of protein gels based on bovine gelatin and keratin hydrolysates obtained from leather industry byproducts were used for periodical application on the tomato plant roots in the early stage of vegetation. The gels were characterized by classical physicochemical methods and protein secondary structure was obtained by FTIR band deconvolution. After ripening, tomato was analyzed regarding its content of quality indicators (sugars and organic acids) and antioxidants (lycopene, ß-carotene, vitamin C, polyphenols). The results emphasized the positive effects of the protein gels on the quality parameters of tomato fruit. An increase of 10% of dry matter and of 30% (in average) in the total soluble sugars was noted after biostimulant application. Also, lycopene and vitamin C recorded higher values (by 1.44 and 1.29 times, respectively), while ß-carotene showed no significant changes. The biostimulant activity of protein gels was correlated with their amino acid composition. Plant biostimulants are considered an ecological alternative to conventional treatments for improving plant growth, and also contributing to reduce the intake of chemical fertilizers.

Luminescence, Paramagnetic, and Electrochemical Properties of Copper Oxides-Decorated TiO2/Graphene Oxide Nanocomposites.

The properties of newly synthesized Cu2O/CuO-decorated TiO2/graphene oxide (GO) nanocomposites (NC) were analyzed aiming to obtain insight into their photocatalytic behavior and their various applications, including water remediation, self-cleaning surfaces, antibacterial materials, and electrochemical sensors. The physico-chemical methods of research were photoluminescence (PL), electron paramagnetic resonance (EPR) spectroscopy, cyclic voltammetry (CV), and differential pulse voltammetry (DPV). The solid samples evidenced an EPR signal that can be attributed to the oxygen-vacancy defects and copper ions in correlation with PL results. Free radicals generated before and after UV-Vis irradiation of powders and aqueous dispersions of Cu2O/CuO-decorated TiO2/GO nanocomposites were studied by EPR spectroscopy using two spin traps, DMPO (5,5-dimethyl-1-pyrroline-N-oxide) and CPH (1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine), to highlight the formation of hydroxyl and superoxide reactive oxygen species, respectively. The electrochemical characterization of the NC modified carbon-paste electrodes (CPE) was carried out by CV and DPV. As such, modified carbon-paste electrodes were prepared by mixing carbon paste with copper oxides-decorated TiO2/GO nanocomposites. We have shown that GO reduces the recombination process in TiO2 by immediate electron transfer from excited TiO2 to GO sheets. The results suggest that differences in the PL, respectively, EPR data and electrochemical behavior, are due to the different copper oxides and GO content, presenting new perspectives of materials functionalization.

Bioactivity and Thermal Stability of Collagen-Chitosan Containing Lemongrass Essential Oil for Potential Medical Applications.

Bioactive collagen-chitosan-lemongrass (COL-CS-LG) membranes were prepared by casting method and analyzed for potential biomedical applications. For COL-CS-LG membranes, LG essential oil release, antioxidant properties, in vitro cytotoxicity and antimicrobial assessments were conducted, as well as free radical determination after gamma irradiation by chemiluminescence, and structural characteristics analysis through Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) and Differential Scanning Calorimetry (DSC). The evaluation of non-isothermal chemiluminescence after gamma radiation exposure to COL-CS-LG membranes revealed a slowing down of the oxidation process at temperatures exceeding 200 °C, in correlation with antioxidant activity. Antimicrobial properties and minimum inhibitory concentrations were found to be in correlation with cytotoxicity limits, offering the optimum composition for designing new biomaterials.

Gamma Irradiation and Ag and ZnO Nanoparticles Combined Treatment of Cotton Textile Materials.

In this work, cotton textile materials were impregnated by immersion with three different nanocomposites: Ag/chitosan, Ag/polyvinylpyrrolidone, and ZnO/polyvinylpyrrolidone and irradiated with a 60Co gamma source. After the nanoparticles impregnation, the cotton materials were irradiated in a dry and wet state at 5 and 20 kGy radiation doses. The following methods were used for the characterization of the obtained cotton materials to reveal the modification of the textile materials: Fourier transform infrared-attenuated total reflection spectroscopy (FTIR-ATR) and thermogravimetry (TG). The obtained materials have good antibacterial properties. The microbiological tests have shown the best material results for the gamma irradition and Ag nanoparticles combined treatment. The objective was to create a more environmentally friendly approach for textile functionalization by eliminating toxic chemicals-based technology and replacing it with the eco-friendlier gamma technology.

Bioactive Low Molecular Weight Keratin Hydrolysates for Improving Skin Wound Healing.

Keratin biomaterials with high molecular weights were intensively investigated but few are marketed due to complex methods of extraction and preparation and limited understanding of their influence on cells behavior. In this context the aim of this research was to elucidate decisive molecular factors for skin homeostasis restoration induced by two low molecular weight keratin hydrolysates extracted and conditioned through a simple and green method. Two keratin hydrolysates with molecular weights of 3758 and 12,400 Da were physico-chemically characterized and their structure was assessed by circular dichroism (CD) and FTIR spectroscopy in view of bioactive potential identification. Other investigations were focused on several molecular factors: α1, α2 and ß1 integrin mediated signals, cell cycle progression in pro-inflammatory conditions (TNFα/LPS stimulated keratinocytes and fibroblasts) and ICAM-1/VCAM-1 inhibition in human vascular endothelial cells. Flow cytometry techniques demonstrated a distinctive pattern of efficacy: keratin hydrolysates over-expressed α1 and α2 subunits, responsible for tight bounds between fibroblasts and collagen or laminin 1; both actives stimulated the epidermal turn-over and inhibited VCAM over-expression in pro-inflammatory conditions associated with bacterial infections. Our results offer mechanistic insights in wound healing signaling factors modulated by the two low molecular weight keratin hydrolysates which still preserve bioactive secondary structure.

Compatibility of Drotaverine Hydrochloride with Ibuprofen and Ketoprofen Nonsteroidal Anti-Inflammatory Drugs Mixtures.

Formulations with two or more active pharmaceutical ingredients (APIs) are a researched trend due to their convenient use compared with multiple medications. Moreover, drug-drug combinations may have a synergistic effect. Drotaverine hydrochloride (D-HCl) is commonly used for its antispasmodic action. The combination of a spasmolytic and an analgesic drug such as ibuprofen (Ibu) or ketoprofen (Ket) could become the answer for the treatment of localized pain. D-HCl:Ibu and D-HCl:Ket drug-drug interactions leading to the formation of eutectic compositions with increased bioavailability, obtained by mechanosynthesis, a green, solvent-free method was explored for the first time. The compatibility of Ibuprofen, Ketoprofen, and Drotaverine Hydrochloride was investigated using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-Transform Infrared spectroscopy (FTIR). Solid-liquid equilibrium (SLE) phase diagrams for the binary systems of active pharmaceutical ingredients were developed and the Tammann diagrams were designed to determine the eutectic compositions. The excess thermodynamic functions GE for the pre-, post-, and eutectic compositions were obtained using the computed activity coefficients data. Results show that drotaverine-based pharmaceutical forms for pain treatment may be obtained at 0.9 respectively 0.8 molar fractions of ibuprofen and ketoprofen which is advantageous because the maximum allowed daily dose of Ibu is about 6 times higher than those of D-HCl and Ket. The obtained eutectics may be a viable option for the treatment of pain associated with cancer therapy.

Thermal Behavior of the Nimesulide-Salicylic Acid Eutectic Mixtures Prepared by Mechanosynthesis and Recrystallization.

Nimesulide, salicylic acid and their binary mixtures were studied by differential scanning calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The study of such systems is a promising and viable approach for solving the problem of poor solubility of materials in general and drug systems in particular. All areas of human activity are inextricably linked to materials, and thus, the study presented in the paper and not reported in the literature is very important and provides useful data for those working in various fields. The eutectic mixtures were obtained by mechanosynthesis and by recrystallization from ethanol over the entire 0-1 range of molar fractions. For both situations at the molar fraction of nimesulide 0.5, the mixture has a eutectic that suggests an increase in solubility at this composition. The interactions that take place between the components were determined with the help of the excess thermodynamic functions (GE, SE, µE), which highlight the deviation from the ideality of the considered binary systems.

Application of Amberlite IRA 402 Resin Adsorption and Laccase Treatment for Acid Blue 113 Removal from Aqueous Media.

Despite Acid Blue 113 (AB 113)'s extensive use and negative environmental impact, very few studies have focused on its efficient and environmentally friendly removal. This research aims the removal of AB 113 from environmental aqueous media and its consequent enzymatic biodegradation. A strongly basic anion exchange resin in Cl- form, Amberlite IRA 402 (IRA 402(Cl-)) was used for AB 113 adsorption and a laccase was used to further biodegrade it. For the first time, two novel, efficient and environmentally friendly physical-chemical and biological assays for AB 113 wastewater removal and subsequent biodegradation were combined. The adsorption of AB 113 onto IRA 402(Cl-) was tested in batch and continuous flux modes. Influence of contact time, concentration and desorption in acidic media were evaluated. The kinetic data were best modulated by the Lagergren model with R2 = 0.9275. The Langmuir isotherm model best fitted the experimental data, and the maximum adsorption capacity was 130 mg/g. Dye, resin and AB113 loaded resin were characterized by thermogravimetry and FTIR to evaluate their physical chemical properties modification. Based on the performed studies, a consecutive methodology is proposed, incorporating the ion exchange process in the first stage and the biodegradation process in the second. Thus, in the second stage the residual concentration of AB 113 is reduced by an efficient bio-degradation process produced by the laccase at pH = 4.

Wool Keratin Hydrolysates for Bioactive Additives Preparation.

The aim of this paper was to select keratin hydrolysate with bioactive properties by using the enzymatic hydrolysis of wool. Different proteolytic enzymes such as Protamex, Esperase, and Valkerase were used to break keratin molecules in light of bioactive additive preparation. The enzymatic keratin hydrolysates were assessed in terms of the physico-chemical characteristics related to the content of dry substance, total nitrogen, keratin, ash, cysteic sulphur, and cysteine. The influence of enzymatic hydrolysis on molecular weight and amino acid composition was determined by gel permeation chromatography (GPC) and gas chromatography-mass spectrometry (GC-MS) analyses. Antimicrobial activity of keratin hydrolysates was analysed against Fusarium spp., a pathogenic fungus that can decrease the quality of plants. The bioactivity of enzymatic hydrolysates was tested on maize plants and allowed us to select the keratin hydrolysates processed with the Esperase and Valkerase enzymes. The ratio of organised structures of hydrolysate peptides was analysed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) deconvolution of the amide I band and may explain the difference in their bioactive behaviour. The most important modifications in the ATR spectra of maize leaves in correlation with the experimentally proven performance on maize development by plant length and chlorophyll index quantification were detailed. The potential of enzymatic hydrolysis to design additives with different bioactivity was shown in the case of plant growth stimulation.

Multifunctional Leather Surface Design by Using Carbon Nanotube-Based Composites.

This paper deals with original research in smart leather surface design for the development of multifunctional properties by using multi-walled carbon nanotube (MWCNT)-based nanocomposites. The conductive properties were demonstrated for both sheepskin and bovine leather surfaces for 0.5% MWCNTs in finishing nanocompositions with prospects for new material design intended for flexible electronics or multifunctional leathers. The photocatalytic properties of bovine leather surface treated with 0.5% MWCNTs were shown against an olive oil stain after visible light exposure and were attributed to reactive oxygen species generation and supported by contact angle measurements in dynamic conditions. The volatile organic compounds' decomposition and antibacterial tests confirmed the self-cleaning experimental conclusions. Ultraviolet protection factor had excellent values for leather surfaces treated with multi-walled carbon nanotube and the fastness resistance tests showed improved performance compared to control samples. Scanning electron microscopy with energy dispersive X-ray (SEM-EDX), X-ray photoelectron spectroscopy (XPS), and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy analysis confirmed the influence of different leather surfaces on MWCNT dispersion with an effect on nanoparticle reactivity and efficiency in self-cleaning properties. Multifunctional leather surfaces were designed and demonstrated through MWCNT-based nanocomposite use under conventional finishing conditions.

Maize Stalk Material for On-Site Treatment of Highly Polluted Leachate and Mine Wastewater.

New research applications involving the use of cellulosic material derived from maize stalk for on-site treatment of leachate were evaluated for specific removal of Cu(II) and Fe(III) from real, highly polluted tailing pond and mine wastewater samples. Two major issues generated by anthropic mining activities were also tackled: wastewater metal content decrease to improve water quality and subsequently metal specific recovery, increasing the economic efficiency of metal production by using a green technology for residual management. Rapid saturation of the maize stalk mass determined in batch studies and the mine pilot experiment led to diminished metal concentrations in the second pilot experiment, where Cu(II) and Pb(II) from synthetic solutions were monitored in order to test biomaterial performances. In addition, in the second pilot experiment, maize stalk removed Pb(II) in the first 36 h, below the determination limit of the analytical method. The biomaterial bed in the column was saturated after 252 h of inflow solution. FTIR-ATR, TG and SEM techniques probed the interaction between maize stalk polar groups C=O, -OH, C-O and tailing water metallic ions by large FTIR band displacements, intensity decrease and shape changes, modification of thermal stability and by changes in the appearance of adsorbent microstructure images owing mainly to ion exchange mechanism.

Investigation of the Effects of Rapid Thermal Annealing on the Electron Transport Mechanism in Nitrogen-Doped ZnO Thin Films Grown by RF Magnetron Sputtering.

Nitrogen-doped ZnO (ZnO:N) thin films, deposited on Si(100) substrates by RF magnetron sputtering in a gas mixture of argon, oxygen, and nitrogen at different ratios followed by Rapid Thermal Annealing (RTA) at 400 °C and 550 °C, were studied in the present work. Raman and photoluminescence spectroscopic analyses showed that introduction of N into the ZnO matrix generated defects related to oxygen and zinc vacancies and interstitials. These defects were deep levels which contributed to the electron transport properties of the ZnO:N films, studied by analyzing the current-voltage characteristics of metal-insulator-semiconductor structures with ZnO:N films, measured at 298 and 77 K. At the appliedtechnological conditions of deposition and subsequent RTA at 400 °C n-type ZnO:N films were formed, while RTA at 550 °C transformed the n-ZnO:N films to p-ZnO:N ones. The charge transport in both types of ZnO:N films was carried out via deep levels in the ZnO energy gap. The density of the deep levels was in the order of 1019 cm-3. In the temperature range of 77-298 K, the electron transport mechanism in the ZnO:N films was predominantly intertrap tunneling, but thermally activated hopping also took place.

Synthesis, density functional theory study and in vitro antimicrobial evaluation of new benzimidazole Mannich bases.

The tri-component synthesis of novel chiral benzimidazole Mannich bases, by reaction between benzimidazole, aqueous 30% formaldehyde and an amine, the biological evaluation and DFT studies of the new compounds are reported here. The 1H-NMR, 13C-NMR, FTIR spectra and elemental analysis confirm the structures of the new compounds. All synthesized compounds were screened by qualitative and quantitative methods for their in vitro antibacterial activity against 4 bacterial strains. DFT studies were accomplished using GAMESS 2012 software and HOMO-LUMO analysis allowed the calculation of electronic and structural parameters of the chiral Mannich bases. The geometry of 1-methylpiperazine, the cumulated Mullikan atomic charges of the two heteroatoms and of the methyl, and the value of the global electrophilicity index (ω = 0.0527) of the M-1 molecule is correlated with its good antimicrobial activity. It was found that the presence of saturated heterocycles from the amine molecule, 1-methyl piperazine and morpholine, respectively, contributes to an increased biological activity, compared to aromatic amino analogs, diphenylamino-, 4-nitroamino- and 4-aminobenzoic acid. The planarity of the molecules, specific bond lengths and localization of HOMO-LUMO orbitals is responsible for the best biological activities of the compounds.

Total assignment and structure in solution of tetrandrine by NMR spectroscopy and molecular modelling.

High-resolution 1- and 2D NMR spectra of tetrandrine and molecular modelling were employed to characterise its structure in solution. Complete and unambiguous assignment of all proton and carbon resonance signals is reported. Scalar couplings were determined from dihedral angles with the Karplus equation. Inter-proton distances were evaluated from NOE correlation peaks. Comparison of simulated and X-ray conformations of tetrandrine reveals only small differences.