New Copper Complexes with Antibacterial and Cytotoxic Activity.

The discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu+2 complexes, [Cu4(L1)4(OH)4(DMF)2(H2O)] (C1) (HL1 = N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-benzenesulfonamide) and [Cu(L2)2(phen)(H2O)] (C2) (HL2 = N-(5-(4-methylphenyl)-[1,3,4]-thiadiazole-2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu+2 is five-coordinated, forming a CuN2O3 and CuN4O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single Nthiadiazole atom; for the two complexes, the molecules from the reaction medium (phenantroline, dimethylformamide and water) are also involved in the coordination of Cu+2. The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR and UV-Vis spectroscopy. Using the microdilution method, the antibacterial activity of the complexes was determined against four Gram-positive and two Gram-negative bacteria, with Gentamicin as the positive control. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, DLD-1) and on a normal cell line (HFL1) using the MTT method and Cisplatin as a positive control. Flow cytometric assessment of apoptosis induced by the complexes on the three cell lines was also performed. Both complexes present in vitro biological activities but complex C2 is more active.

Influence of the Structure on Magnetic Properties of Calcium-Phosphate Systems Doped with Iron and Vanadium Ions.

The aim of this study was to prepare and characterize the glasses made of x(Fe2O3∙V2O5)∙(100 - x)[P2O5∙CaO] with x ranging of 0-50%. The contribution of Fe2O3 and V2O5 amount on the structure of P2O5·CaO matrix was investigated. The vitreous materials were characterized by XRD (X-ray diffraction analysis), EPR (Electron Paramagnetic Resonance) spectroscopy, and magnetic susceptibility measurements. A hyperfine structure typical for isolated V4+ ions was noticed to all spectra containing low amount of V2O5. The XRD spectra show the amorphous nature of samples, apart x = 50%. An overlap of the EPR spectrum of a broad line without the hyperfine structure characteristic of clustered ions was observed with increasing V2O5 content. The results of magnetic susceptibility measurements explain the antiferromagnetic or ferromagnetic interactions expressed between the iron and vanadium ions in the investigated glass.

Structural Insights and Intermolecular Energy for Some Medium and Long-Chain Testosterone Esters.

Testosterone (17ß-Hydroxyandrost-4-en-3-one) is the primary male anabolic-androgenic steroid. The crystal structures of two medium and two long esterified forms of testosterone, including enanthate, cypionate, decanoate and undecanoate, were determined by X-ray single crystal diffraction. The samples were also characterized by powder X-ray diffraction, FT-IR spectroscopy and thermal analysis (DTA, TG). Crystal packings and supramolecular features were described. The analysis of structural features was accomplished by computational methods in terms of the type of intermolecular interactions, crystal energies and Hirshfeld surfaces analysis. From a pharmaceutical point of view, the solubility of compounds was investigated.

Crystal Structure and Intermolecular Energy for Some Nandrolone Esters.

Nandrolone (Estr-4-en-17ß-ol-3-one) is a derivative of testosterone and a naturally occurring anabolic-androgenic agent which belongs to the steroid group. Crystal structures of four short, medium and long esterified forms of nandrolone, including propionate, phenylpropionate, cypionate and undecanoate were determined using single-crystal X-ray diffraction. Crystal packing, supramolecular features and intermolecular interactions were described based on a quantitative and qualitative Hirshfeld surfaces analysis accompanied by evaluation of crystal energies and intermolecular interactions computation. Also, the solubility of the esters was investigated from a pharmaceutical perspective.

New Cu+2 Complexes with N-Sulfonamide Ligands: Potential Antitumor, Antibacterial, and Antioxidant Agents.

Nowadays, the discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu+2 complexes, [Cu(L1)2(H2O)3] (C1) (HL1= N-(5-(4-methylphenyl)-[1,3,4]-thiadiazole-2-yl)-naphtalenesulfonamide) and [Cu(L2)2(py)2(H2O)] (C2) (HL2= N-(5-ethyl-[1,3,4]-thiadiazole-2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu+2 is five-coordinated, forming a CuN2O3 and CuN4O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single Nthiadiazole atom; for the C2 complex, the molecules from the reaction medium (pyridine and water) are also involved in the coordination of Cu+2. The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR, electronic EPR spectroscopy, and magnetic methods. The nuclease activity studies confirm the complexes' capacity to cleave the DNA molecule. Using a xanthine-xanthine oxydase system, the SOD mimetic activity of the complexes was demonstrated. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, WM35) and on a normal cell line (HFL1) using the MTT method, with cisplatin used as a positive control. The antibacterial activity of the complexes was investigated against two Gram-positive and two Gram-negative bacteria, and compared with Amoxicillin and Norfloxacin using the disk diffusion method. Both complexes showed in vitro biological activity but the C2 complex was more active. A lack of in vivo toxicity was demonstrated for the C2 complex by performing hepatic, renal, and hematological studies on Swiss mice.

ß-Ketophosphonates with Pentalenofuran Scaffolds Linked to the Ketone Group for the Synthesis of Prostaglandin Analogs.

ß-Ketophosphonates with pentalenofurane fragments linked to the keto group were synthesized. The bulky pentalenofurane skeleton is expected to introduce more hindrance in the prostaglandin analogues of type III, greater than that obtained with the bicyclo[3.3.0]oct(a)ene fragments of prostaglandin analogues I and II, to slow down (retard) the inactivation of the prostaglandin analogues by oxidation of 15α-OH to the 15-keto group via the 15-PGDH pathway. Their synthesis was performed by a sequence of three high yield reactions, starting from the pentalenofurane alcohols 2, oxidation of alcohols to acids 3, esterification of acids 3 to methyl esters 4 and reaction of the esters 4 with lithium salt of dimethyl methanephosphonate at low temperature. The secondary compounds 6b and 6c were formed in small amounts in the oxidation reactions of 2b and 2c, and the NMR spectroscopy showed that their structure is that of an ester of the acid with the starting alcohol. Their molecular structures were confirmed by single crystal X-ray determination method for 6c and XRPD powder method for 6b.

Eco-Friendly Nitrogen-Doped Graphene Preparation and Design for the Oxygen Reduction Reaction.

Four N-doped graphene materials with a nitrogen content ranging from 8.34 to 13.1 wt.% are prepared by the ball milling method. This method represents an eco-friendly mechanochemical process that can be easily adapted for industrial-scale productivity and allows both the exfoliation of graphite and the synthesis of large quantities of functionalized graphene. These materials are characterized by transmission and scanning electron microscopy, thermogravimetry measurements, X-ray powder diffraction, X-ray photoelectron and Raman spectroscopy, and then, are tested towards the oxygen reduction reaction by cyclic voltammetry and rotating disk electrode methods. Their responses towards ORR are analysed in correlation with their properties and use for the best ORR catalyst identification. However, even though the mechanochemical procedure and the characterization techniques are clean and green methods (i.e., water is the only solvent used for these syntheses and investigations), they are time consuming and, generally, a low number of materials can be prepared, characterized and tested. In order to eliminate some of these limitations, the use of regression learner and reverse engineering methods are proposed for facilitating the optimization of the synthesis conditions and the materials' design. Thus, the machine learning algorithms are applied to data containing the synthesis parameters, the results obtained from different characterization techniques and the materials response towards ORR to quickly provide predictions that allow the best synthesis conditions or the best electrocatalysts' identification.

Exploring the Polymorphism of Drostanolone Propionate.

2α-Methyl-4,5α-dihydrotestosterone 17ß-propionate, known as drostanolone propionate or masteron, is a synthetic anabolic-androgenic steroid derived from dihydrotestosterone. The crystal structures of two polymorphs of drostanolone propionate have been determined by single crystal X-ray diffraction and both crystallizes in the monoclinic crystal system. One is belonging to the P21 space group, Z = 2, and has one molecule in the asymmetric unit while the second belongs to the I2 space group, Z = 4, and contains two molecules in the asymmetric unit. Another polymorph has been investigated by an X-ray powder diffraction method and solved by Parallel tempering/Monte Carlo technique and refined with the Rietveld method. This polymorph crystallizes in the orthorhombic P212121 space group, Z = 4 having one molecule in the asymmetric unit. The structural configuration analysis shows that the A, B, and C steroid rings exist as chair geometry, while ring D adopts a C13 distorted envelope configuration in all structures. For all polymorphs, the lattice energy has been computed by CLP (Coulomb-London-Pauli), and tight-binding density functional theory methods. Local electron correlation methods were used to estimate the role of electron correlation in the magnitude of the dimer energies. The nature of the intermolecular interactions has been analyzed by the SAPT0 energy decomposition methods as well as by Hirshfeld surfaces.

X-ray Crystal Structure, Geometric Isomerism, and Antimicrobial Activity of New Copper(II) Carboxylate Complexes with Imidazole Derivatives.

Five new copper(II) acrylate complexes (acr is the acrylate anion: C3H3O2) with imidazole derivatives (2-methylimidazole/2-MeIm, 5-methylimidazole/5-MeIm, 2-ethylimidazole/2-EtIm) of type: cis-[Cu(2-RIm)2(acr)2]·xH2O ((1): R = ⁻CH3, x = 2; (4): R = ⁻CH2⁻CH3, x = 0), trans-[Cu(2-RIm)2(acr)2] ((2): R = ⁻CH3; (5): R = ⁻CH2⁻CH3) and trans-[Cu(5-RIm)2(acr)2] ((3): R = ⁻CH3) have been prepared and characterized by elemental analysis, Fourier Transform Infrared spectrometry (FTIR), Electron Paramagnetic Resonance (EPR), electronic reflectance spectroscopy, scanning electron microscopy, and mass spectrometry. The single crystal X-ray diffraction study of complexes (2) and (5) reveals that the copper(II) ion is located on an inversion center and show elongated octahedral geometry completed by two coplanar bidentate acrylates and two unidentate imidazole derivatives displayed in trans positions. For complex (4) the single crystal X-ray diffraction shows that the copper(II) ion is in a distorted octahedral environment which can be easily confused with a trigonal prism completed by two bidentate acrylates and two unidentate imidazole derivatives displayed in cis positions. These results indicate the fact that complexes (4) and (5) are the geometric isomers of the same compound bis(acrylate)-bis(2-ethylimidazole)-copper(II). Complexes (1) and (2), as well as (4) and (5), were produced simultaneously in the reaction of the corresponding copper(II) acrylate with imidazole derivatives in methanol solution. Furthermore, in order to be able to formulate potential applications of the obtained compounds, our next goal was to investigate the in vitro antimicrobial activity of the synthesized complexes against Gram-positive and Gram-negative bacteria, as well as fungal strains, of both clinical and ecological importance (biodeterioration of historical buildings). The trans isomers (2) and (5), followed by (4) have shown the broadest range of antimicrobial activity. In case of (1) and (2) isomers, the trans isomer (2) was significantly more active than cis (1), while the cis isomer (4) proved to be more active than trans (5). Taken together, the biological evaluation results indicate that the trans (2) was the most active complex, demonstrating its potential for the development of novel antimicrobial agents, with potential applications in the biomedical and restoration of architectural monuments fields.

Graphene-bimetallic nanoparticle composites with enhanced electro-catalytic detection of bisphenol A.

This study brings for the first time novel knowledge about the synthesis by catalytic chemical vapor deposition with induction heating of graphene-bimetallic nanoparticle composites (Gr-AuCu and Gr-AgCu) and their morphological and structural characterization by transmission electron microscopy, Raman spectroscopy, and x-ray powder diffraction. Gold electrodes modified with the obtained materials exhibit an enhanced electro-catalytic effect towards one of the most encountered estrogenic disruptive chemicals, bisphenol A (BPA). The BPA behavior in varying pH solutions was investigated using the electrochemical quartz crystal microbalance, which allowed the accurate determination of the number of molecules involved in the oxidation process. The modified electrodes promote the oxidation of BPA at significantly lower potentials (0.66 V) compared to bare gold (0.78 V). In addition, the peak current density recorded with such electrodes greatly exceeded that obtained with bare gold (e.g. one order of magnitude larger, for a Au/Gr-AgCu electrode). The two modified electrodes have low detection limits, of 1.31 × 10-6 M and 1.91 × 10-6 M for Au/Gr-AgCu and Au/Gr-AuCu, respectively. The bare gold electrode has a higher detection limit of 5.1 × 10-6 M. The effect of interfering species (e.g. catechol and 3-nitrophenol) was also investigated. Their presence influenced not only the BPA peak potential, but also the peak current. With both modified electrodes, no peak currents were recorded below 3 × 10-5 M BPA.

Five Novel Polymorphs of Cardarine/GW501516 and Their Characterization by X-ray Diffraction, Computational Methods, Thermal Analysis and a Pharmaceutical Perspective.

GW501516, also known by the name of cardarine, is a synthetic peroxisome-proliferator-activated receptor delta (PPR-δ) agonist agent developed for applications in the treatment of metabolic disorders and cardiovascular diseases. A broad polymorph screening in various solvents and mixtures was completed in order to explore its capabilities to grow polymorphs. The crystal structures of four polymorphs were elucidated using single-crystal X-ray diffraction, while one structure was solved via a powder X-ray diffraction method. The solid state features (nature of intermolecular interactions) were investigated by computational methods. The polymorphs were further investigated by thermal DSC analysis and X-ray diffraction on powders. From a pharmaceutical perspective, the stability and solubility of the polymorphs were analyzed as well.

Green Synthesis of Gold, Silver, Copper, and Magnetite Particles Using Poly(tartaric acid) Simultaneously as Coating and Reductant.

Poly(tartaric acid) is a relatively recently described polymer that can be easily synthesized and scaled up from a readily available renewable material (tartaric acid). This article demonstrates its use in a green synthesis of gold nanoparticles, silver nanoparticles, copper particles, and magnetite nanoparticles. In this case poly(tartaric acid) acts both as a reductant and as a coating agent. To our knowledge this is the first green synthesis of several different types of nanoparticles using only one reagent (polytartrate) as both reductant and coating. The resulting particles were analyzed by XRD, TEM/SEM, EDX, FTIR, DLS, zeta-potential, XPS, and UV/VIS spectroscopy. Preliminary studies of the thermal behavior of mixtures of different types of particles with poly(tartaric acid) were also conducted. The obtained particles show different sizes depending on the material, and the coating allows for better dispersibility as well as potential further functionalization, making them potentially useful also for other applications, besides the inclusion in polymer composites.

Ag and Sn Implications in 3-Polker Coins Forgeries Evidenced by Nondestructive Methods.

Several forged 3-Polker coins have been reported in historical sources on the financial crisis that occurred between 1619 and 1623 at the start of the 30-year-long war. Supposedly, belligerent countries forged other countries' coins which were then used for external payments as a war strategy. Thus, a lot of 3-Polker coins (e.g., Sigismund-III-type) were forged, and the markets became flooded with poor currency. In the present day, these pre-modern forgeries are rare archeological findings. Only five forged 3-Polker coins randomly found in Transylvania were available for the current study. There are deeper implications of silver and tin in the forgery techniques that need to be considered. Thus, the forged 3-Polker coins were investigated via nondestructive methods: SEM microscopy coupled with EDS elemental spectroscopy for complex microstructural characterization and XRD for phase identification. Three distinct types of forgery methods were identified: the amalgam method is the first used for copper blank silvering (1620), and immersion in melted silver (1621) is the second one. Both methods were used to forge coins with proper legends and inscriptions. The third method is the tin plating of copper coins (with corrupted legend and altered design) (1622, 1623, and 1624). The EDS investigation revealed Hg traces inside the compact silver crusts for the first type and the elongated silver crystallites in the immersion direction, which are well-attached to the copper core for the second type. The third forgery type has a rich tin plating with the superficial formation of Cu6Sn5 compound that assures a good resistance of the coating layer. Therefore, this type should have been easily recognized as fake by traders, while the first two types require proper weighing and margin clipping to ensure their quality.

Development of Diclofenac Sodium 3D Printed Cylindrical and Tubular-Shaped Tablets through Hot Melt Extrusion and Fused Deposition Modelling Techniques.

The present study aimed to develop 3D printed dosage forms, using custom-made filaments loaded with diclofenac sodium (DS). The printed tablets were developed by implementing a quality by design (QbD) approach. Filaments with adequate FDM 3D printing characteristics were produced via hot melt extrusion (HME). Their formulation included DS as active substance, polyvinyl alcohol (PVA) as a polymer, different types of plasticisers (mannitol, erythritol, isomalt, maltodextrin and PEG) and superdisintegrants (crospovidone and croscarmellose sodium). The physicochemical and mechanical properties of the extruded filaments were investigated through differential scanning calorimetry (DSC), X-ray diffraction (XRD) and tensile measurements. In addition, cylindrical-shaped and tubular-shaped 3D dosage forms were printed, and their dissolution behaviour was assessed via various drug release kinetic models. DSC and XRD results demonstrated the amorphous dispersion of DS into the polymeric filaments. Moreover, the 3D printed tablets, regardless of their composition, exhibited a DS release of nearly 90% after 45 min at pH 6.8, while their release behaviour was effectively described by the Korsmeyer-Peppas model. Notably, the novel tube design, which was anticipated to increase the drug release rate, proved the opposite based on the in vitro dissolution study results. Additionally, the use of crospovidone increased DS release rate, whereas croscarmellose sodium decreased it.

Material Evidence of Sediments Recovered from Ancient Amphorae Found at the Potaissa Roman Fortress.

Methods for material investigation are powerful tools that allow specialists to elucidate important aspects regarding ancient artifacts such as the Roman amphorae deposits discovered at Potaissa Fortress in Turda, Romania. Archeological debate states that the deposit contained olive oil and wine amphorae, but no material evidence has been presented until now. The current research is focused on the most representative large amphora fragments found in the Potaissa deposit, with a significant amount of sediment on their walls, to give archeologists the material proof to elucidate their debate. Sediment was collected from each fragment and subjected to complex analysis. XRD investigation combined with cross-polarized light microscopy demonstrated mineral particles such as quartz, clay (muscovite and traces of biotite), and calcite. Quartz and calcite particles have a rounded shape and diameters in a range of 20-200 µm, and clay particles have a lamellar shape and dimensions from 1 to 20 µm, a fact confirmed by SEM microscopy. Sample 2 presented a large amount of amorphous phase followed by Samples 1 and 3, with a low amount of organic phase. FTIR investigation confirms organic phase presence owing to strong absorption bands regarding C-H, C=O, and O-H chemical bonds related to aliphatic compounds in Sample 2, and to some decayed wine residue in Samples 1 and 3. EDS elemental analysis was used for organic particle identification in the amphora sediments and to obtain a correlation with their microstructure. GC-MS investigation showed volatile compounds related to wine residue for Samples 1 and 3 and decomposed fats for Sample 2. Tartaric and malic acid were identified by HPLC in Samples 1 and 3, which are wine biomarkers. The correlation of all experimental results concludes with no doubt that Amphora 2 contained olive oil and Amphorae 1 and 3 contained wine in ancient times.

In Vitro and In Vivo Characterisation of a Mucoadhesive Buccal Film Loaded with Doxycycline Hyclate for Topical Application in Periodontitis.

Mucoadhesive films loaded with doxycycline hyclate (Doxy Hyc), consisting of mixtures of hydroxypropylmethyl cellulose (HPMC) E3, K4 and polyacrylic acid (Carbopol 940), were prepared by casting method, aiming to design a formulation intended for application in the oral cavity. The obtained film formulations exhibited a Doxy Hyc content between 7.52 ± 0.42 and 7.83 ± 0.41%, which had adequate mechanical properties for application in the oral cavity and pH values in the tolerance range. The x-ray diffraction studies highlighted the amorphisation of Doxy Hyc in the preparation process and the antibiotic particles present on the surface of the films, identified in the TEM images, which ensured a burst release effect in the first 15 min of the in vitro dissolution studies, after which Doxy Hyc was released by diffusion, the data presenting a good correlation with the Peppas model, n < 0.5. The formulation F1, consisting of HPMC K4 combined with C940 in a ratio of 5:3, the most performing in vitro, was tested in vivo in experimentally-induced periodontitis and demonstrated its effectiveness in improving the clinical parameters and reducing the salivary levels of matrix metalloproteinase-8 (MMP-8). The prepared Doxy Hyc loaded mucoadhesive buccal film could be used as an adjuvant for the local treatment of periodontitis, ensuring prolonged release of the antibiotic after topical application.

Structure of the inclusion complex of ß-cyclodextrin with lipoic acid from laboratory powder diffraction data.

The crystal structure of the inclusion complex of ß-cyclodextrin with lipoic acid was determined from laboratory powder diffraction data. Thermogravimetric data was used to estimate the number of water molecules in the crystal structure. Lipoic acid is included in ß-cyclodextrin through its primary face with the five-membered ring reaching the center plane of the cyclodextrin cavity and its fatty acid chain adopting a bent conformation. Lipoic acid and ß-cyclodextrin form a channel-like packing which is stabilized by guest-host hydrogen bonding and close contacts, host-host intermolecular interactions and hydrogen bonding involving the water molecules.

Complexation of Amlodipine Besylate with ß-Cyclodextrin.

In this paper the procedure for the preparation of inclusion compounds of bioactive substance 2-[(2-aminoetoxy)-methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridine dicarboxylic acid 3-ethyl-5-methyl esterbenzene sulfonate, called amlodipine besylate with ß-cyclodextrin (ß-CD) and their structural characterization was described. Molecular inclusion compound of amlodipine besylate is obtained by different preparation method: kneading, co-precipitation and freeze-drying. The so obtained compounds were investigated by FTIR spectroscopy, X-ray diffraction method and differential scanning calorimetric measurements (DSC) to evidence their formation. Molecular modeling (using DFT theoretical computations) shows the spatial architecture of the inclusion compound in good agreement with FTIR experimental data: the drug is included with dihydropyridine dicarboxylate part inside ß-cyclodextrin cavity. The inclusion of amlodipine besylate in ß-cyclodextrin increases the stability and bioavailability of the drug.

N-Butyl-4-butyl-imino-2-methyl-pentan-2-aminium (E)-quercetinate.

The title salt, C(14)H(31)N(2) (+)·C(15)H(9)O(7) (-), was obtained in the reaction of quercetin with n-butyl-amine in a mixture of acetone and hexane. The crystal structure determination shows that the quercetin donates one of its phenol H atoms to the N-butyl-4-butyl-imino-2-methyl-pentan-2-amine mol-ecule. The crystal structure of the salt is stabilized by intramolecular (N-H⋯N for the cation and O-H⋯O for the anion) and intermolecular hydrogen bonding (N-H⋯O between cation-anion pairs and O-H⋯O between anions). Quercetin molecules form dimers connected into a two-dimensional network. The dihedral angle between the quercetin ring systems is 19.61 (8)°.

Structural Aspects and Intermolecular Energy for Some Short Testosterone Esters.

Testosterone (17ß-hydroxyandrost-4-en-3-one) is the primary naturally occurring anabolic-androgenic steroid. The crystal structures of three short esterified forms of testosterone, including propionate, phenylpropionate, and isocaproate ester, were determined via single-crystal X-ray diffraction. Furthermore, all the samples were investigated using powder X-ray diffraction, and their structural features were described and evaluated in terms of crystal energies and Hirshfeld surfaces. They were also compared with the base form of testosterone (without ester) and the acetate ester. Moreover, from a pharmaceutical perspective, their solubility was evaluated and correlated with the length of the ester.