Search

The synthesis and structural characterization of three families of coordination complexes synthesized from 4′‐phenyl‐2,2′:6′,2′′‐terpyridine (8, Ph‐TPY), 4′‐(4‐chlorophenyl)‐2,2′:6′,2′′‐terpyridine (9, ClPh‐TPY) and 4′‐(4‐methoxyphenyl)‐2,2′:6′,2′′‐terpyridine (10, MeOPh‐TPY) ligands with the divalent metals Co2+, Fe2+, Mn2+ and Ni2+ are reported. The compounds were synthesized from a 1:2 mixture of the metal and ligand, resulting in a series of complexes with the general formula [M(R‐TPY)2](ClO4)2 (where M = Co2+, Fe2+, Mn2+ and Ni2+, and R‐TPY = Ph‐TPY, ClPh‐TPY and MeOPh‐TPY). The general formula and structural and supramolecular features were determinated by single‐crystal X‐ray diffraction for bis(4′‐phenyl‐2,2′:6′,2′′‐terpyridine)nickel(II) bis(perchlorate), [Ni(C21H15N3)2](ClO4)2 or [Ni(Ph‐TPY)2](ClO4)2, bis[4′‐(4‐methoxyphenyl)‐2,2′:6′,2′′‐terpyridine]manganese(II) bis(perchlorate), [Mn(C22H17N3O)2](ClO4)2 or [Mn(MeOPh‐TPY)2](ClO4)2, and bis(4′‐phenyl‐2,2′:6′,2′′‐terpyridine)manganese(II) bis(perchlorate), [Mn(C21H15N3)2](ClO4)2 or [Mn(Ph‐TPY)2](ClO4)2. In all three cases, the complexes present distorted octahedral coordination polyhedra and the crystal packing is determined mainly by weak C—H...π interactions. All the compounds (except for the Ni derivatives, for which FT–IR, UV–Vis and thermal analysis are reported) were fully characterized by spectroscopic (FT–IR, UV–Vis and NMR spectroscopy) and thermal (TGA–DSC, thermogravimetric analysis–differential scanning calorimetry) methods. [ABSTRACT FROM AUTHOR]

The water‐soluble compound [Ru3O(CH3COO)6(4‐ampy)3]Cl (1, 4‐ampy=4‐aminopyridine) was evaluated in terms of its biologically relevant properties. Compound 1 participates in a hydrogen bonding network which includes the NH2 substituents of the ancillary ligands, methanol molecules, the Cl− counter‐ion, and a non‐conventional hydrogen bond with the neighboring 4‐ampy molecules′ π‐cloud, as determined by X‐ray measurements. One protonation equilibrium was observed at pH values below 2.3. Additionally, the compound exhibited a partition coefficient value of −0.86 (±0.07), indicating that it is highly hydrophilic. At 37 0C and pH=7.4 (phosphate buffer), compound 1 shows moderate (Ksv=2.4 104 M−1) and spontaneous (ΔG=−26.4 kJ mol−1) binding to human serum albumin (HSA) through ground‐state association, which involves formation of hydrogen bonds (ΔH=−35.7 kJ mol−1 and, ΔS=−29.8 J mol−1 K−1). Molecular docking calculations support the formation of hydrogen bonds between 1 and HSA, and suggest subdomain IIA (site I), which contains the Trp‐214 residue, as the primary interactive pocket, in agreement with the experimental static fluorescence quenching mechanism. Furthermore, a preliminary assay reveals that 1 has low cytotoxicity towards human glioblastoma U87‐MG cells. [ABSTRACT FROM AUTHOR]

The chemical reaction of 4-bromo-benzoyl-chloride and 2-amino-thia-zole in the presence of potassium thio-cyanate yielded a white solid formulated as C15H10BrN3OS2, which consists of 4-bromo-benzamido and 2-benzo-thia-zolyl moieties connected by a thio-urea group. The 4-bromo-benzamido and 2-benzo-thia-zolyl moieties are in a trans conformtion (sometimes also called s-trans due to the single bond) with respect to the N-C bond. The dihedral angle between the mean planes of the 4-bromo-phenyl and the 2-benzo-thia-zolyl units is 10.45 (11)°. The thio-urea moiety, -C-NH-C(=S) -NH- fragment forms a dihedral angle of 8.64 (12)° with the 4-bromo-phenyl ring and is almost coplanar with the 2-benzo-thia-zolyl moiety, with a dihedral angle of 1.94 (11)°. The mol-ecular structure is stabilized by intra-molecular N-H⋯O hydrogen bonds, resulting in the formation of an S(6) ring. In the crystal, pairs of adjacent mol-ecules inter-act via inter-molecular hydrogen bonds of type C-H⋯N, C-H⋯S and N-H⋯S, resulting in mol-ecular layers parallel to the ac plane. [ABSTRACT FROM AUTHOR]

Lapachol (lap) is widely studied due to its biological application, as well as its importance in the coordination chemistry field. The structure of cis and trans isomers of new ruthenium(III) complex [RuCl2(PPh3)2(lap)] is reported here. The complexes present one molecule of the natural product lapachol, coordinated as bidentate by oxygen atoms, two monodentate triphenylphosphines and two chlorido ligands in a cis or trans configurations. All neutral complexes were characterized by single-crystal X-ray diffraction and these data were compared with Density Functional Theory (DFT) data results. This study highlights the stereochemistry and structural versatility of metal complexes containing lapachol as ligand. [ABSTRACT FROM AUTHOR]

A three-dimensional terbium(III) coordination polymer of formula [Tb(bttb)0.5(2,5-pzdc)0.5]n (1) [H4bttb = 1,2,4,5-tetrakis(4′-carboxyphenyl)benzene and H2-2,5-pzdc = 2,5-pyrazinedicarboxylic acid] was obtained under hydrothermal conditions. The bttb4− tetraanion in 1 adopts the bridging and chelating–bridging pseudo-oxo coordination modes while the 2,5-pzdc2− dianion exhibits a rather unusual bis-bidentate bridging pseudo-oxo coordination mode, both ligands being responsible for the stiffness of the resulting 3D structure. Solid-state photoluminescent measurements illustrate that 1 exhibits remarkable green luminescence emission, the most intense band occurring in the region of 550 nm (5D4 → 7F5) with lifetimes at the millisecond scale. Thermometric performances of 1 reveal a maximum relative sensitivity (Sm) of 0.76% K−1 at 295 K (δT = 0.05 K), constituting a TbIII ratiometric solid luminescent thermometer over the physiological temperature range. Variable-temperature static (dc) magnetic susceptibility measurements for 1 in the temperature range 2.0–300 K show the expected behavior for the depopulation of the splitted mJ levels of the 7F7 ground state of the magnetically anisotropic terbium(III) ion plus a weak antiferromagnetic interaction through the carboxylate bridges. No significant out-of-phase magnetic susceptibility signals were observed for 1 in the temperature range 2.0–10.0 K, either in the absence or presence of a static dc magnetic field. [ABSTRACT FROM AUTHOR]

This study addressed the formation of co‐crystals from Quercetin and Curcumin by mechanochemical treatment employing ball mill grinding. The binary system was initially studied using molecular complementarity and hydrogen bond propensity analysis structural tools available in Mercury software. This study was performed from CCDC reported structural data for Curcumin and Quercetin dihydrate used as starting reagents. Reaction conditions, such as Quercetin: Curcumin molar ratio, grinding time, and solvent‐assisted variables, were optimised to synthesise a new solid phase from the binary system. The synthesised product was characterised by differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, and powder X‐ray diffraction techniques. Finally, to compare the anti‐oxidant capacities from the pure components, eutectic mixtures previously reported and the new crystalline phase was evaluated in vitro using the 1,1‐diphenyl‐2‐pycril‐hydrazylhydrate radical inhibition method. The co‐crystal phase and eutectic mixtures present higher anti‐oxidant activity with values around 5.0 mg/L compared to pure Quercetin (3,444 mg/L) and Curcumin (9,141 mg/L), using only half of the molecules. These results indicate Quercetin molecule is synergically active with the Curcumin molecule in the binary mixtures. [ABSTRACT FROM AUTHOR]

Coordination compounds of copper exhibit cytotoxic activity and are suitable for the search for novel drug candidates for cancer treatment. In this work, we synthesized three copper(II) carboxylate complexes, [Cu2(3-(4-hydroxyphenyl)propanoate)4(H2O)2]·2H2O (C1), [Cu2(phenylpropanoate)4(H2O)2] (C2) and [Cu2(phenylacetate)4] (C3), and characterized them by elemental analysis and spectroscopic methods. Single-crystal X-ray diffraction of C1 showed the dinuclear paddle-wheel arrangement typical of Cu–carboxylate complexes in the crystal structure. In an aqueous solution, the complexes remain as dimeric units, as studied by UV-visible spectroscopy. The lipophilicity (partition coefficient) and the DNA binding (UV visible and viscosity) studies evidence that the complexes bind the DNA with low Kb constants. In vitro cytotoxicity studies on human cancer cell lines of metastatic breast adenocarcinoma (MDA-MB-231, MCF-7), lung epithelial carcinoma (A549) and cisplatin-resistant ovarian carcinoma (A2780cis), as well as a nontumoral lung cell line (MRC-5), indicate that the complexes are cytotoxic in cisplatin-resistant cells. [ABSTRACT FROM AUTHOR]

This study reports on the synthesis and characterization of two new coordination compounds of the active pharmaceutical ingredient metformin and transition metals. The cobalt compound with the formula [Co(Met)3][CoCl4]Cl·3H2O is a complex salt formed by a cationic Co(III) octahedral and anionic Co(II) tetrahedral subunits. The Cu(II) complex is represented by the formula [(Cu(Met)Cl)2-μ-Cl2] and is a dimeric compound with two chloride anions acting as a bridge, forming shared-edge square pyramidal units. Both compounds were characterized by single crystal X-ray diffraction, FT-IR spectroscopy and thermal analysis. [ABSTRACT FROM AUTHOR]

Herein, we report on the synthesis and characterization of ruthenium compounds with the general formula [RuCl(AA-H)(NO)(dppb]PF6, where AA = glycine (1), L-alanine (2), L-phenylalanine (3) and L-valine (4), and dppb = 1,4-bis(diphenylphosphine)butane. The complexes were characterized using elemental analysis, UV/Vis and infrared spectroscopies, 1H, 13C, 31P NMR techniques, and cyclic voltammetry. Furthermore, the structures of the compounds (1) and (3) were determined using single-crystal X-ray diffraction. In vitro evaluation of the Ru(II)/nitrosyl/amino acid complexes revealed their cytotoxic activities against triple-negative MDA-MB-231 breast cancer cells, and against the non-tumor murine fibroblast cells. All the compounds decreased the percentage of viable cells, inducing cell death by apoptosis. Additionally, the Ru(II) complexes inhibited the migration of MDA-MB-231 cells at concentrations lower than 35 µM, after 48 h of exposure. Thus, these complexes may be promising agents for the treatment of triple-negative MDA-MB-231 breast cancer. [ABSTRACT FROM AUTHOR]

Coordination complexes may act as anticancer agents. Among others, the formation of the complex may facilitate the ligand uptake by the cell. Searching for new copper compounds with cytotoxic activity, the complex Cu-dipicolinate was studied as a neutral scaffold to form ternary complexes with diimines. A series of [Cu(dipicolinate)(diimine)] complexes (where diimine: Phenanthroline, phen, 5-NO2-phenanthroline, 4-methyl-phenanthroline, neocuproine, 3,4,7,8-tetramethyl-phenanthroline, tmp, bathophenanthroline, bipyridine, dimethyl-bipyridine, as well as the ligand 2,2-dipyridil-amine, bam) were synthesized and characterized both in the solid state, including a new crystal structure of [Cu2(dipicolinate)2(tmp)2]·7H2O. Their chemistry in aqueous solution was explored by UV/vis spectroscopy, conductivity, cyclic voltammetry, and electron paramagnetic resonance studies. Their DNA binding was analyzed by electronic spectroscopy (determining Kb values), circular dichroism, and viscosity methods. The cytotoxicity of the complexes was assessed on human cancer cell lines MDA-MB-231, MCF-7 (breast, the first triple negative), A549 (lung epithelial) and A2780cis (ovarian, Cisplatin-resistant), and non-tumor cell lines MRC-5 (lung) and MCF-10A (breast). The major species are ternary, in solution and solid state. Complexes are highly cytotoxic as compared to Cisplatin. Complexes containing bam and phen are interesting candidates to study their in vivo activity in triple-negative breast cancer treatment. [ABSTRACT FROM AUTHOR]

Drug repurposing is becoming interesting in terms of offering advantages over the traditional drug development, once drug discovery is a costly, time-consuming, and highly risky process. In particular, with the coronavirus disease (COVID-19) declared by World Health Organization as a global pandemic, there has emerged a considerable need to develop therapeutic agents capable of preventing viral outbreaks. Concomitantly, well-known and long-used drugs such as acyclovir (Acv) have been tested against COVID-19. Acv is a guanosine analogue that acts as an antiviral drug, commonly used to treat herpes simplex virus (HSV), genital herpes, and varicella zoster virus (VZV). Acv showed to inhibit viral proteases, multiple viral genes expression, and RNA-Dependent RNA Polymerase, helping to recover COVID-19 patients. However, ACV is a BCS class III/IV drug, with low permeability and/or slight water solubility (concentration-dependent). Given the repurposing eligibility of Acv, in this work, two new salts of this drug are presented (nitrate and sulfate), with the aim of improving its pharmacokinetic properties. The new salts were evaluated by X-ray diffraction, and thermal and spectroscopic analyses. A third salt, a chloride one, was also characterized and used for comparison. [ABSTRACT FROM AUTHOR]

In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (ortho-quinone/para-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of para-naphthoquinones and subsequent conjugation with different ortho-quinoidal moieties. As anticipated, our study identified several compounds with IC50 values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized para-quinones coupled with ortho-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango! [ABSTRACT FROM AUTHOR]

Searching for new copper compounds which may be useful as antitumor drugs, a series of new [Cu(L-dipeptide)(batho)] (batho:4,7-diphenyl-1,10-phenanthroline, L-dipeptide: Gly-Val, Gly-Phe, Ala-Gly, Ala-Ala, Ala-Phe, Phe-Ala, Phe-Val and Phe-Phe) complexes were synthesized and characterized. To interpret the experimental IR spectra, [Cu(ala-gly)(batho)] was modelled in the gas phase using DFT at the B3LYP/LANL2DZ level of theory and the calculated vibrational frequencies were analyzed. Solid-state characterization is in agreement with pentacoordinate complexes of the general formula [Cu(L-dipeptide)(batho)]·x solvent, similar to other [Cu(L-dipeptide)(diimine)] complexes. In solution, the major species are heteroleptic, as in the solid state. The mode of binding to the DNA was evaluated by different techniques, to understand the role of the diimine and the dipeptide. To this end, studies were also performed with complexes [CuCl2(diimine)], [Cu(L-dipeptide)(diimine)] and free diimines, with phenanthroline, neocuproine and 3,4,7,8-tetramethyl-phenanthroline. The cytotoxicity of the complexes was determined on human cancer cell lines MDA-MB-231, MCF-7 (breast, the first triple negative), and A549 (lung epithelial) and non-tumor cell lines MRC-5 (lung) and MCF-10A (breast). [Cu(L-dipeptide)(batho)] complexes are highly cytotoxic as compared to cisplatin and [Cu(L-dipeptide)(phenanthroline)] complexes, being potential candidates to study their in vivo activity in the treatments of aggressive tumors for which there is no curative pharmacological treatment. [ABSTRACT FROM AUTHOR]

Immunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-N-acyl hydrazones derivatives (SintMed(141–156). The evaluated N-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC50 values greater than 50 µM. In addition, all ferrocenyl-N-acyl hydrazones modulated nitrite production in immortalized macrophages, showing inhibition values between 14.4% and 74.2%. By presenting a better activity profile, the ferrocenyl-N-acyl hydrazones SintMed149 and SintMed150 also had their cytotoxicity and anti-inflammatory effect evaluated in cultures of peritoneal macrophages. The molecules were not cytotoxic at any of the concentrations tested in peritoneal macrophages and were able to significantly reduce (p < 0.05) the production of nitrite, TNF-α, and IL-1β. Interestingly, both molecules significantly reduced the production of IL-2 and IFN-γ in cultured splenocytes activated with concanavalin A. Moreover, SintMed150 did not show signs of acute toxicity in animals treated with 50 or 100 mg/kg. Finally, we observed that ferrocenyl-N-acyl hydrazone SintMed150 at 100 mg/kg reduced the migration of neutrophils (44.6%) in an acute peritonitis model and increased animal survival by 20% in an LPS-induced endotoxic shock model. These findings suggest that such compounds have therapeutic potential to be used to treat diseases of inflammatory origin. [ABSTRACT FROM AUTHOR]

BACKGROUND: The purpose of this work was to investigate the potential use of zinc‐dithiocarbimate salts to control Hemileia vastatrix, the causal agent of the coffee leaf rust disease, and to evaluate their toxicity towards Apis mellifera, one of the most important coffee plant pollinators. RESULTS: Zinc‐dithiocarbimate salts were prepared and fully characterized by infrared, proton (1H) and carbon‐13 (13C) nuclear magnetic resonance and elemental analyses of carbon (C), hydrogen (H), nitrogen (N) and zinc (Zn). X‐ray diffraction technique studies confirmed the proposed structures. The salts inhibited the germination of H. vastatrix spores in vitro, with a 50% inhibitory concentration (IC50) from 12 to 18 μmol.L−1 and a 90% inhibitory concentration (IC90) from 23 to 26 μmol.L−1. Zinc‐dithiocarbimate salts with the best in vitro results were selected for in vivo experiments with Coffea arabica var Caturra and with the pollinator A. mellifera. The results were similar to those of Mancozeb, a broad‐spectrum contact fungicide, with a good control of the disease and low toxicity to the honeybee. CONCLUSION: The zinc‐dithiocarbimate complex salts have potential to control coffee leaf rust, with low toxicity to the pollinator insect. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The synthesis and XRD characterization at 295 K of three isomers, X-fluoro-N-(2-hydroxy-5-methyl phenyl) benzamide: (o-FPhB), (m-FPhB), and (p-FPhB), are presented. o-FPhB and m-FPhB show high structural affinity concerning molecular and packing structures. The planarity of the C1-C7(O1)-N1-C8 peptide bond in o-FPhB, and m-FPhB confers high stability, favoring its tendency to acquire a resonant structure in the peptide segment and in the molecule. For p-FPhB, a stereochemical gate opens, leading to the activation of N-H∙∙∙∙O interpeptide bonds, defining its supramolecular properties. Active participation of the halogen in the assembly of the structures is observed, forming intramolecular rings and molecule chains during crystal growth. The o-FPhB and m-FPhB form parallel sheets that develop hydrogen C-H···Cg, halogen C-F···Cg, or C=O···Cg interactions. Theoretical evaluations of the properties performed by the DFT/B3LYP/(6-311G(d,p) showed good agreement with the experimental values. The IR analysis reaffirms the presence of N-H, C=O, O-H, C-F, and C-H. In the UV-Vis, an increase in the energetic stability, O···H interactions, and electrostatic potential in the NH region reaffirm the disposition of p-FPhB for the formation of the N-H···O interpeptide bond. A molecular docking on the benzamides involving protein receptors showed similar behavior for all three isomers. [ABSTRACT FROM AUTHOR]

New compounds to fight cancer are needed due to cancer high incidence and lack of curative treatments for several classes of this disease. Metal-based coordination compounds offer a variety of molecules that can turn into drugs. Among them, coordination copper complexes are emerging as an attractive class of compounds for cancer treatment. A series of [Cu(l-dipeptide)(tmp)] (tmp = 3,4,7,8-tetramethyl-1,10-phenanthroline) complexes were synthesized and characterized in the solid state, including the determination of the crystalline structure of [Cu(Gly-Gly)(tmp)]·3.5 H2O and [Cu2Cl4(tmp)2]. The complexes were studied in solution, where the major species are also ternary ones. The lipophilicity of the complexes was determined and the binding to the DNA was evaluated, suggesting that it occurs in the DNA's major groove. The cytotoxicity of the complexes was evaluated on different cancer cell lines: human metastatic breast adenocarcinoma MDA-MB-231 (triple negative, ATCC: HTB-26), MCF-7 (ATCC: HTB-22), SK-BR-3 (ATCC: HTB-30), human lung epithelial carcinoma A549 (ATCC: CCL-185), cisplatin resistant-human ovarian carcinoma A2780cis (SIGMA) and nontumoral cell lines: MRC-5 (lung; ATCC: CCL-171) and MCF-10A (breast, ATCC: CRL-10317). [Cu(l-dipeptide)(tmp)] complexes are highly cytotoxic as compared to [Cu(l-dipeptide)(phenanthroline)] and cisplatin. Therefore, [Cu(l-dipeptide)(tmp)] complexes are promising candidates to have their in vivo activity further studied toward new treatments for triple negative breast cancer and other aggressive tumors for which there is no curative pharmacological treatment to the date. [ABSTRACT FROM AUTHOR]

Three principal factors may influence the final structure of coordination polymers (CPs): (i) the nature of the ligand, (ii) the type and coordination number of the metal center, and (iii) the reaction conditions. Further, flexible carboxylate aliphatic ligands have been widely employed as building blocks for designing and synthesizing CPs, resulting in a diverse array of materials with exciting architectures, porosities, dimensionalities, and topologies as well as an increasing number of properties and applications. These ligands show different structural features, such as torsion angles, carbon backbone number, and coordination modes, which affect the desired products and so enable the generation of polymorphs or crystalline phases. Additionally, due to their large coordination numbers, using 4f and 5f metals as coordination centers combined with aliphatic ligands increases the possibility of obtaining different crystal phases. Additionally, by varying the synthetic conditions, we may control the production of a specific solid phase by understanding the thermodynamic and kinetic factors that influence the self-assembly process. This revision highlights the relationship between the structural variety of CPs based on flexible carboxylate aliphatic ligands and f-elements (lanthanide and actinides) and their outstanding luminescent properties such as solid-state emissions, sensing, and photocatalysis. In this sense, we present a structural analysis of the CPs reported with the oxalate ligand, as the one rigid ligand of the family, and other flexible dicarboxylate linkers with –CH2– spacers. Additionally, the nature of the luminescence properties of the 4f or 5f-CPs is analyzed, and finally, we present a novel set of CPs using a glutarate-derived ligand and samarium, with the formula [2,2′-bipyH][Sm(HFG)2 (2,2′-bipy) (H2O)2]•(2,2′-bipy) (α-Sm) and [2,2′-bipyH][Sm(HFG)2 (2,2′-bipy) (H2O)2] (β-Sm). [ABSTRACT FROM AUTHOR]

This study reports the synthesis, structural characterization and cytotoxic activity of four new palladium/pyridylporphyrin complexes, with the general formula {TPyP[PdCl(P–P)]4}(PF6)4, where P–P is 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,2-bis(diphenylphosphino)butane (dppb) or 1,1′-bis(diphenylphosphino)ferrocene (dppf). The complexes were characterized by elemental analysis, and by FT-IR, UV/Vis, 1H and 31P{1H} NMR (1D/2D) spectroscopy. The slow evaporation of a methanolic solution of {TPyP[PdCl(dppb)]4}(PF6)4 (in an excess of NaBF4 salt) resulted in single crystals suitable for X ray diffraction, allowing the determination of the tridimensional structure of this complex, which crystallized in the P21/a space group. The cytotoxicity of the complexes against MDA-MB-231 (breast cancer cells) and MCF-10A (non-tumor breast cancer cells), was determined by the colorimetric MTT method, which revealed that all four complexes show selective indexes close to 1.2, lower than that of cisplatin for the same cells (12.12). The interaction of the complexes with CT-DNA was evaluated by UV-visible and viscosity measurements and it was determined that the complexes interact moderately with CT-DNA, probably by H-bonding/π–π stacking and electrostatic interactions. [ABSTRACT FROM AUTHOR]

The coordination ability of the antisecretor agent Famotidine (FMT) was explored using Ni(II) as central ion. [NiFMTH-2] and [Ni(FMT)2]Cl2 were obtained by the solvent evaporation method from the corresponding starting solutions at pH 8 and 4, respectively; the crystal structure was elucidated by single crystal X-ray diffraction in both cases.[NiFMTH-2] resulted in a distorted square-planar geometry, where FMT acts as a tetradentate dianionic ligand through nitrogen atoms belonging to the guanidine group, the thiazolic ring and the side chain, and a sulfur atom from the thioether moiety. [Ni(FMT)2]Cl2 exhibits an octahedral environment composed by two FMT molecules that coordinate by nitrogen atoms deriving from guanidine and thiazole ring moieties, and the thioether sulfur atom. The physicochemical characterization was completed by means of FTIR and UV–Vis spectroscopies, and thermal analysis. Solubility measurements were performed and the results could be satisfactorily correlated with the solvation Gibbs free energy (ΔGsolv) values in aqueous solution obtained using the SDM model by DFT calculations. Ni(II) and famotidine form an octahedral complex at pH 4 where famotidine acts as a tridentate neutral ligand. In basic medium, it behaves as a tetradentate dianion, resulting in a quasi-planar complex. Spectroscopic and thermal data are consistent with single crystal X-ray diffraction structural elucidation. The relative stabilities were assessed by theoretical studies. [ABSTRACT FROM AUTHOR]

Copyright of Revista Colombiana de Química is the property of Universidad Nacional de Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Here we discovered an unprecedented giant octahedral coordination compound bearing 16 Zn2+, 12 Na+, 8 O2−, 4 OH−, 13 H2O and 6 L4− ligands [L4− = fully deprotonated tetra(carboxymethoxy)calix[4]arene]. Its structure was elucidated by single-crystal X-ray diffraction, wavelength-dispersive X-ray spectroscopy and MALDI-TOF mass spectrometry. This compound, Zn8Na6L6⊃Zn8Na6O8(OH)4(H2O)13 (external⊃internal), has eight tetrahedral zinc ions forming the coordination vertices of an outermost cube where carboxylate groups from the sodium calixarenes are anchored. Its core consists of eight Zn2+, six Na+, eight O2−, and four OH− distributed over three layers, besides thirteen coordinated H2O molecules. [ABSTRACT FROM AUTHOR]

Complexes with general formula [RuCl(η6-p-cymene)(P–NR–P)]X (R = CH2Py (Py = pyridine) – [1a]+, CH2Ph (Ph = phenyl) – [1b]+, Ph – [1c] and p-tol (p-tol = p-tolyl) – [1d]+; X = PF6− or BF4−) were evaluated as cytotoxic agents against two cancer cell lines (HeLa and MDA-MB-231). All metal complexes are active in the range of concentrations tested (up to 100 μmol L−1). The IC50 (μmol L−1) values for the metal complexes are lower than that found for cisplatin. The activities are up to 6- and 15-fold higher than cisplatin for HeLa and MDA-MB-231 cancer cell lines, respectively. Studies of DNA binding and DNA cleavage were performed. DNA binding studies revealed a modest hypochromic shift in the metal complexes electronic spectra, indicating a weak interaction with Kb values in the range of 1.7 × 103–1.6 × 104. Although the cleavage tests revealed that in the dark DNA is not a biological target for these metal complexes, upon blue light irradiation they are activated causing DNA cleavage. Electrochemical studies showed the presence of two independent redox processes, one attributed to the oxidation process of Ru2+ → Ru3+ (EC process) and the other one to the reduction of Ru2+ → Ru1+, which is further reduced to Ru0 (ECE mechanism). In both processes, coupled chemical reactions were observed. DFT calculations were performed to support the electrochemical/chemical behavior of the complexes. The reactivity of complex [1b]BF4 with CH3CN was evaluated and two complexes were isolated [2b]BF4 and [3b]BF4. The complex mer-[RuCl(CH3CN)3(P–NCH2Ph–P)]BF4 ([2b]BF4) was isolated after refluxing the precursor [1b]BF4 in CH3CN. Isomerization of [2b]BF4 in CH3CN resulted in the formation of fac-[RuCl(CH3CN)3(P–NCH2Ph–P)]BF4. An attempt to isolate the fac-isomer by adding diethyl ether was unsuccessful, and the complex [3b]BF4 was observed as the major component. The complex [Ru2(μ-Cl3)(CH3CN)2(P–NCH2Ph–P)2]BF4 ([3b]BF4) proved to be very stable and can be obtained from both the mer- and the fac-isomers. The molecular structures of [1b]BF4 and [3b]BF4 were solved by single-crystal X-ray diffraction. [ABSTRACT FROM AUTHOR]

Novel silver(I) complexes of the type [AgCl(PPh3)2(L)] {PPh3 = triphenylphosphine; L = VTSC = 3-methoxy-4-hydroxybenzaldehyde thiosemicarbazone (1); VMTSC = 3-methoxy-4-[2-(morpholine-1-yl)ethoxy]benzaldehyde thiosemicarbazone (2); VPTSC = 3-methoxy-4-[2-(piperidine-1-yl)ethoxy]benzaldehyde thiosemicarbazone (3)} were synthesized and fully characterized by spectroscopic techniques. The molecular structures of complexes 2 and 3 were determined by single crystal X-ray diffraction. Compounds 1–3 exhibited appreciable cytotoxic activity against human tumor cells (lung A549, breast MDA-MB-231 and MCF-7) with IC50 values in 48 h of incubation ranging from 5.6 to 18 μM. Cellular uptake studies showed that complexes 1–3 were efficiently internalized after 3 hours of treatment in MDA-MB-231 cells. The effects of complex 1 on the cell morphology, cell cycle, induction of apoptosis, mitochondrial membrane potential (Δψm), and reactive oxygen species (ROS) production have been evaluated in triple negative breast cancer (TNBC) cells MDA-MB-231. Our results showed that complex 1 induced typical morphological alterations of cell death, an increase in cells at the sub-G1 phase, apoptosis, and mitochondrial membrane depolarization. Furthermore, DNA binding studies evidenced that 1 can bind to ct-DNA and does so without modifying the B-structure of the DNA, but that the binding is weak compared to that of Hoechst 33258. [ABSTRACT FROM AUTHOR]

In this work, a study of the secondary porosity of two zeolite‐based composites is carried out by small angle X‐ray scattering (SAXS) and N2 adsorption at 77 K. The composites were obtained by the inclusion of ZnO nanoparticles in a Cuban natural clinoptilolite by mechanosynthesis and 'in situ' methods. It was observed a decrease in the specific surface area as a result of ZnO nanoparticles inclusion from 149 m2 g−1 in the started material to 60 m2 g−1 in the composite prepared by in situ method, whereas the mesopore diameter remained almost constant. The results confirmed the presence of mesopores with diameter between 3 and 36 nm, with good match by both methodologies. These materials were developed in view of their future application as catalysts and adsorbents, where the presence of secondary porosity is key to favor the diffusion processes. [ABSTRACT FROM AUTHOR]

Two novel bicomponent solid forms of mebendazole (MBZ) were developed as a means to modulate its psychochemical and pharmaceutical properties. Supramolecular synthesis of MBZ A or C with perchloric or methyl sulfuric acids yields two salts of 1 : 1 stoichiometry, which were analyzed through single crystal X-ray diffraction. MBZ perchlorate crystallizes in the P21/n space group, while MBZ methyl sulfate crystallizes in the P1¯ space group. The API and its counterions are interconnected in both crystal packings by an R 22 (8) supramolecular motif. The 3-dimensional crystal structure is also stabilized by other strong intermolecular hydrogen bonds as well as non-classical interactions. FT-IR spectra are consistent with the inclusion of the anions in the crystal structure. MBZ perchlorate is stable up to 210 °C when it undergoes endothermic loss of the ester moiety. MBZ methyl sulfate is stable up to 160 °C when endothermic elimination of the methylcarbamate moiety occurs. The solubility behavior of MBZ perchlorate, studied by UV-visible spectroscopy, suggests an improvement by a factor of seven with respect to MBZ A, in the apparent solubility of MBZ in 0.1 mol L−1 HCl. Further experiments are required to evaluate both the stability of the solids and the maximum solubility of the API. [ABSTRACT FROM AUTHOR]

In this study, we report our contribution to the application of whole cells of Brazilian marine-derived fungi in the biotransformation of ethinylestradiol 1. A preliminary screening with twelve marine-derived fungi strains revealed that the fungus Penicillium oxalicum CBMAI 1996 promoted the biotransformation of ethinylestradiol 1. Then, P. oxalicum CBMAI 1996 was employed in the reactions in decaplicate in order to purify and characterize the main biotransformation products of ethinylestradiol 1. Compounds 1b and 1c were characterized by NMR, HRMS, [α]D and mp. Compound 1b was also characterized by single crystal X-ray diffraction. In addition, kinetic monitoring of the biotransformation of ethinylestradiol 1 by P. oxalicum CBMAI 1996 was evaluated in this study in order to obtain high yields of compounds 1b and 1c with a reduction of the reaction time. In this work, we proposed a biotransformation pathway of ethinylestradiol 1, which suggests the presence of several enzymes such as phenol oxidases, monooxygenases, and ene-reductases in the fungus P. oxalicum CBMAI 1996. In summary, the rapid biodegradation of ethinylestradiol 1 and compounds 1b and 1c also has an environmental relevance, since ethinylestradiol 1 and other steroidal compounds are improperly discarded in the environment, and part of these compounds are displaced into the oceans. [ABSTRACT FROM AUTHOR]

A new imidazolium hydrated salt (DCF–IMI–H2O) of the nonsteroidal anti-inflammatory drug diclofenac (DCF) was synthesized by solvent evaporation. This salt was fully characterized by X-ray diffraction (SCXRD and PXRD), infrared spectroscopy (FT-IR) and thermal analysis (TGA, DSC, and HSM) techniques. The salt formation is driven by deprotonation of the drug's carboxylic group, with proton transfer to the nitrogen atom of the imidazole ring. The water molecule plays an important role in the 3D arrangement observed in the crystal lattice, acting as a bridge between adjacent DCF and coformer molecules. DCF–IMI–H2O exhibits an improved solubility profile when compared with the pure form of DCF, and similar values when compared with sodium and potassium salts. This new salt proved stable under 75% relative humidity for one week and is stable after six-months of storage under ambient conditions. The study of its thermal stability showed that a dehydration process starts at around 45 °C, leading to the probable formation of an unstable anhydrous form, which melts around 92 °C. Spectroscopy studies showed that most of the salt is ionized when in an amorphous state (liquid). These behaviors feature the new compound as an ionic liquid (IL), i.e., organic salt with a melting point below 100 °C. Pharmaceutical ILs have been increasingly exploited in the past few years due to their improved properties regarding drug solubility, formulation and delivery (topical, transdermal and oral). Thus, the salt depicted herein becomes a potent candidate for development of novel/improved DCF delivery systems. [ABSTRACT FROM AUTHOR]

We employed (Z)‐N'‐[phenyl(pyrimidin‐2‐yl)methylene]nicotinohydrazide (2) and (Z)‐4‐(dimethylamino)‐N'‐[phenyl(pyrimidin‐2‐yl)methylene]benzohydrazide (3) as cores of dynamic chemical systems whose different states are modulated, in a reversible fashion, through specific physical and chemical stimuli. The structure of the compounds was determined by Nuclear Magnetic Resonance (NMR) techniques (1D and 2D) and confirmed by single‐crystal X‐ray diffraction. By Variable temperature (VT) 1H NMR experiments and DFT calculations, the conformational isomerism of 2 was studied and added as an additional input for the dynamic system. Additionally, 2 exhibits configurational E/Z isomerization mediated by pH variations and UV light. On the other hand, configurational isomerism locks an unlocks a tridentate pocket for metal cation coordination in both 2 and 3. All the different dynamic states configurational/conformational isomerism and locked and unlocked coordination constitute a development in the field of systems of multiple dynamics suitable for molecular machines. [ABSTRACT FROM AUTHOR]

In this work, the 2D Eu(III) coordination polymer {[Eu(HPDC)(PDC)]}n (PDC = 2,6-pyridinedicarboxylate) (1) was prepared in a fast manner via microwave-assisted hydrothermal synthesis. The same compound was obtained by a conventional hydrothermal route and had its structure determined through single crystal X-ray diffraction. In 1, the HPDC and PDC ligands exhibit terminal and chelating bridging modes, respectively, forming a coordination polymer through interconnected europium–carboxylate chains, leading to a highly ordered two-dimensional layer. The nanosheets in 1 self-organize in the solid-state by intermolecular interactions, producing a 3D supramolecular network. Solid-state photoluminescence studies have shown that the antenna effect is responsible for the red emission of the compound under ultraviolet excitation. In alcoholic solutions, it was possible to exfoliate the material by ultrasonication in a top-down approach, leading to single nanosheets of 1. In the chemical stability studies, there was observed a water-induced transformation of 1, leading to the compound {[Eu(PDC)(HPDC)(H2O)2]·4H2O}n (2). The aqueous suspension of this material shows strong red luminescence with the naked-eye. 2 demonstrates reversible behavior induced by heating under reduced pressure. Our work highlights the properties related to solvent-induced exfoliation and water-induced transformation. [ABSTRACT FROM AUTHOR]

Peptidomimetics containing an aziridine moiety have been reported as potent cysteine protease inhibitors. In this sense, the development of stereoselective and sustainable synthetic strategies to obtain three-membered N -heterocyclic compounds has gained importance in the last decades. In this work, an efficient method was designed to achieve highly functionalized aziridine peptidomimetics via a sequential reaction, which involves the organocatalytic aziridination of α,β-unsaturated aldehydes followed by the Passerini multicomponent reaction in an environmentally friendly solvent mixture (ethanol: water). [ABSTRACT FROM AUTHOR]

Although herbicides are essential for ensuring high crop yields, the development of sustainable formulations remains a challenge in modern agriculture. Herbicide use is typically affected by the poor water solubility of the compounds they contain, and so they are often applied at very high doses that exceed those needed for weed control (WC). Highly soluble herbicides allow application without the excessive formation of undissolved solids, but only a few routes have been developed for this purpose. Herein, a crystal engineering approach is presented for improving the solubility of the herbicide ametryn (AMT). Organic salts of AMT with fumaric acid (m.p. ∼ 135 °C) and maleic acid (m.p. ∼ 125 °C) were successfully prepared, providing substantial improvement in the solubility (10-fold and 20-fold, respectively), compared to pure AMT, along with thermal stability. Herbicidal activity tests confirmed the effectiveness of these systems, which showed good WC performance at 1 kg ha−1, considerably below the 2.5 kg ha−1 for AMT. The results demonstrate that these systems offer an accessible technology for reducing the use of AMT in agricultural practices and a strategy for the design of new WC chemistries. [ABSTRACT FROM AUTHOR]

The aim of the present study was to report the crystal structure and spectroscopic, electronic, supramolecular and electrostatic properties of a new polymorph of 4‐(pyridin‐2‐yl)pyrimidin‐2‐amine (C9H8N4). The compound was synthesized under microwave irradiation. The single‐crystal X‐ray structure analysis revealed an angle of 13.36 (8)° between the planes of the rings, as well as molecules linked by Nsp2—H...N hydrogen bonds forming dimers along the crystal. The material was analyzed by FT–IR vibrational spectroscopy, while a computational approach was used to elucidate the vibrational frequency couplings. The existence of Nsp2—H...N hydrogen bonds in the crystal was confirmed spectroscopically by the IR peaks from the N—H stretching vibration shifting to lower wavenumbers in the solid state relative to those in the gas phase. The supramolecular studies confirmed the formation of centrosymmetric R22(8) rings, which correspond to the formation of dimers that stack parallel to the b direction. Other weak C—H...π interactions, essential for crystal growth, were found. The UV–Vis spectroscopic analysis showed a donor–acceptor process, where the amino group acts as a donor and the pyridine and pyrimidine rings act as acceptors. The reactive sites of the molecule were identified and their quantitative values were defined using the electrostatic potential model proposed in the multifunctional wave function analyzer multiwfn. The calculated interaction energies between pairs of molecules were used to visualize the electrostatic terms as the leading factors against the dispersion factors in the crystal‐growth process. The docking results showed that the amino group of the pyrimidine moiety was simultaneously anchored by hydrogen‐bonding interactions with the Asp427 and His407 protein residues. This compound could be key for the realization of a series of syntheses of molecules that could be used as possible inhibitors of chronic myelogenous leukemia. [ABSTRACT FROM AUTHOR]

Two novel multicomponent crystal forms of the prodrug 5-fluorocytosine (5-FC), an ionic cocrystal and a monohydrate salt, with 2,4,6-trinitrophenol (picric acid, PA) and 3,5-dinitrosalicylic acid (DNSA), respectively, were rationally designed and synthesized. Nitro compounds are used to treat many diseases, such as cancer, one of the 5-FC targets via gene-directed prodrug therapy. In addition, within the wide range of applications for nitro compounds is the formation of charge-transfer complexes with organic molecules. Among all 5-FC crystalline structures depicted, only two contain nitro compounds: a salt with PA and a dihydrate cocrystal with 5-nitrouracil. Therefore, the two new single translucent pale gold prism crystals of 5FC-PA and 5FC-DNSA were successfully obtained by slow evaporation from aqueous solution and characterized by X-ray diffraction (single crystal and powder), Fourier Transform Infrared (FT-IR), and Raman (FT-Raman) spectroscopies. In both crystal structures, the 5-FC pyrimidine ring is protonated at the N3 atom and the respective packings are mainly stabilized by N–H⋯O H-bonds. For the 5FC-PA ionic cocrystal, the formation of triple H-bonds (two N–H⋯O and one charge assisted N–H+⋯N H-bonds) among the 5-FC molecules was observed. This is consistent with the expected stability of the duplex structure, which is considered the strongest association between two species. In addition to the structural study, Hirshfeld surface analysis was carried out based on the single crystal X-ray diffraction data. Thermal stability was assessed through thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and hot-stage microscopy (HSM), indicating that these compounds are stable up to approximately 200 °C. The results contribute to the diversity of new 5-FC solid forms and introduce two novel compounds, with possible application in fungal/cancer medicine formulations or to better understand the behavior of cytosine in DNA/RNA base pairing. [ABSTRACT FROM AUTHOR]

Two CuII complexes [Cu(C14H13N4O2)Cl]n, I, and [Cu4(C8H10NO2)4Cl4]n, II, have been synthesized. In the structure of the mononuclear complex I, each ligand is coordinated to two metal centers. The basal plane around the CuII cation is formed by one chloride anion, one oxygen atom, one imino and one pyridine nitro­gen atom. The apical position of the distorted square-pyramidal geometry is occupied by a pyridine nitro­gen atom from a neighbouring unit, leading to infinite one-dimensional polymeric chains along the b-axis direction. Each chain is connected to adjacent chains by inter­molecular C—HO and C—HCl inter­actions, leading to a three-dimensional network structure. The tetra­nuclear complex II lies about a crystallographic inversion centre and has one core in which two CuII metal centers are mutually inter­connected via two enolato oxygen atoms while the other two CuII cations are linked by a chloride anion and an enolato oxygen. An open-cube structure is generated in which the two open-cube units, with seven vertices each, share a side composed of two CuII ions bridged by two enolato oxygen atoms acting in a μ3-mode. The CuII atoms in each of the two CuO3NCl units are connected by one μ2-O and two μ3-O atoms from deprotonated hydroxyl groups and one chloride anion to the three other CuII centres. Each of the penta­coordinated CuII cations has a distorted NO3Cl square-pyramidal environment. The CuII atoms in each of the two CuO2NCl2 units are connected by μ2-O and μ3-O atoms from deprotonated alcohol hy­droxy groups and one chloride anion to two other CuII ions. Each of the penta­coordinated CuII cations has a distorted NO2Cl2 square-pyramidal environment. In the crystal, a series of intra­molecular C—H···O and C—H···Cl hydrogen bonds are observed in each tetra­nuclear monomeric unit, which is connected to four tetra­nuclear monomeric units by inter­molecular C—H···O hydrogen bonds, thus forming a planar two-dimensional structure in the (1...01) plane. [ABSTRACT FROM AUTHOR]

Paroxetine hydrochloride, PRX HCl, is an important and widely prescribed antidepressant drug for anxiety and depression treatment. Since hydrochloride salts can cause problems in their manufacture, we have designed organic salts with oxalic, fumaric, maleic and l-tartaric acids based on the NH2+…COO− synthon. All the salts were obtained from an innovative anion exchange method: selective crystallization from a mixture of PRX HCl and an acid in a certain ratio. The crystal structures of paroxetine (PRX) salts with dicarboxylic acids were determined by the single-crystal X-ray diffraction (SCXRD) method and were also analysed by thermogravimetric analysis, differential scanning calorimetry and FT-IR spectroscopy. Except for FUM and MAL acids, all the carboxylic acids form hydrate salts. Oxalate and tartrate salts are formed through the complete protonation of the anion and exhibit a 1 : 2 stoichiometry. All structures have a Z′ ＞ 1 and different conformations are found for the PRX molecules. In general, the ionic units in the salts extend into chains that pack cohesively, via CH…O and CH…π interactions, into layers. The oxalate salt forms a channel structure where H2O molecules are hosted. On the other hand, the presence of water molecules in the tartrate salt allows the packing of ionic layers. The organic salts are thermally more stable than the commercial PRX form, m.p. ＞ 143 °C. They exhibit lower solubility compared to the hydrochloride form. The scientific contributions of this study show the diversity of the PRX solid forms and identify candidates for use in new antidepressant API solid formulations. [ABSTRACT FROM AUTHOR]

In this paper, four new ruthenium complexes, [Ru(N–S)(dppm)2]PF6 (1), [Ru(N–S)(dppe)2]PF6 (2), [Ru(N–S)2(dppp)] (3) and [Ru(N–S)2(PPh3)2] (4) [dppm = 1,1-bis(diphenylphosphino)methane, dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, PPh3 = triphenylphosphine and N–S = 2-mercaptopyrimidine anion] were synthesized and characterized using spectroscopy techniques, molar conductance, elemental analysis, electrochemical techniques and X-ray diffraction. The DNA binding studies were investigated using voltammetry and spectroscopy techniques. The results show that all complexes exhibit a weak interaction with DNA. HSA interaction with the complexes was studied using fluorescence emission spectroscopy, where the results indicate a spontaneous interaction between the species by a static quenching mechanism. The cytotoxicity of the complexes was evaluated against A549, MDA-MB-231 and HaCat cells by MTT assay. Complexes (1) and (2), which are very active against triple negative MDA-MB-231, were subjected to further biological tests with this cell line. The cytotoxic activity triggered by the complexes was confirmed by clonogenic assay. Cell cycle analyses demonstrated marked anti-proliferative effects, especially at the G0/G1 and S phases. The morphological detection of apoptosis and necrosis – HO/PI and Annexin V-FITC/PI assay, elucidated that the type of cell death triggered by these complexes was probably by apoptosis. The in vivo toxicological assessment performed on zebrafish embryos revealed that complexes (1) and (2) did not present embryotoxic or toxic effects during embryonic and larval development showing that they are promising new prototypes of safer and more effective drugs for triple negative breast cancer treatment. [ABSTRACT FROM AUTHOR]

Experimental 13C solid‐state magic‐angle spinning (MAS) Nuclear Magnetic Resonance (NMR) as well as Density‐Functional Theory (DFT) gauge‐including projector augmented wave (GIPAW) calculations were used to probe disorder and local mobility in diethylcarbamazine citrate, (DEC)+(citrate)−. This compound has been used as the first option drug for the treatment of filariasis, a disease endemic in tropical countries and caused by adult worms of Wuchereria bancrofti, which is transmitted by mosquitoes. We firstly present 2D 13C─1H dipolar‐coupling‐mediated heteronuclear correlation spectra recorded at moderate spinning frequency, to explore the intermolecular interaction between DEC and citrate molecules. Secondly, we investigate the dynamic behavior of (DEC)+(citrate)− by varying the temperature and correlating the experimental MAS NMR results with DFT GIPAW calculations that consider two (DEC)+ conformers (in a 70:30 ratio) for crystal structures determined at 293 and 235 K. Solid‐state NMR provides insights on slow exchange dynamics revealing conformational changes involving particularly the DEC ethyl groups. [ABSTRACT FROM AUTHOR]

Purpose: Mechanochemistry is addressed here for the green formation of a 1:1 pharmaceutical cocrystal involving the antifungal prodrug 5-Fluorocytosine (5-FC) and the antineoplastic drug 5-Fluorouracil (5-FU). Crystalline material of this drug-drug cocrystal (DDC) was previously obtained by slow evaporation from solution (SES) and was then structurally analyzed.Method: In this paper, neat grinding and solvent-drop grinding (SDG) were applied in an attempt to achieve a route for the supramolecular synthesis of this cocrystal, exhibiting suitable yield and amount for solid characterization, which were not achieved via the SES method.Results: SDG provided the solid drug-drug cocrystal form. The resulting material had its physical stability monitored for 2 years and was then evaluated by a range of analytical technologies: X-ray powder diffraction, differential scanning calorimetry, hot-stage microscopy, thermogravimetric, and spectroscopic analysis.Conclusions: The new cocrystal proved to be stable for 6 months and in environments with high relative humidity. In this sense, it is believed that the new DDC is a potential model system which could be used as a base for further developments in the field, for other molecules or in relation to the feasibility of using this cocrystal therapeutically. [ABSTRACT FROM AUTHOR]

Fluconazole (FLZ) is one of the most used antifungal drugs worldwide and has been the focus of various investigations with the aim of enhancing its biomedical application. Most of the new solid forms achieved for this drug were determined by powder X-ray diffraction, and a few reports on polymorphs, solvates, cocrystals, and one salt–cocrystal by single-crystal X-ray diffraction (SCXRD) are available. By considering that FLZ is a very weak base (pKa = 1.76, when protonated), salt formation with this drug is expected with the use of very strong organic acids, in order to dislocate the proton from the acid to the FLZ. To the best of our knowledge, only one organic salt of FLZ with picric acid (pKa = 0.38) and one salt–cocrystal (maleate–maleic, pKa1 = 1.92) were reported by SCXRD until now. Having in mind all the advantages that pharmaceutical salts have in drug delivery, in this work we depict the methodology and techniques employed to synthesize a new salt of FLZ using oxalic acid (pKa1 = 1.23). The screening process was initially monitored using Raman spectroscopy, while further characterization by X-ray diffraction (powder and single crystal) and thermal analysis (DSC and TG) was performed to confirm the new salt fluconazolium oxalate (1 : 1). Finally, salt equilibrium solubility studies confirmed an improvement, about 7-fold, when compared to the commercialized active pharmaceutical ingredient (polymorph II). In addition, this is the first reported GRAS (generally regarded as safe) salt of the antifungal drug fluconazole. [ABSTRACT FROM AUTHOR]

Leishmaniasis, a neglected tropical disease caused by protozoans of the genus Leishmania, kills around 20-30 thousand people in Africa, Asia, and Latin America annually and, despite its potential lethality, it can be treated and eventually cured. However, the current treatments are limited owing to severe side effects and resistance development by some Leishmania. These factors make it urgent to develop new leishmanicidal drugs. In the present study, three ruthenium(II) organometallic complexes containing as ligands the commercially available anti-inflammatories diclofenac (dic), ibuprofen (ibu), and naproxen (nap) were synthesized, characterized, and subjected to in vitro leishmanicidal activity. The in vitro cytotoxicity assays against Leishmania (L.) amazonensis and Leishmania (L.) infantum promastigotes have shown that complexes [RuCl(dic)(η6-p-cymene)] (1) and [RuCl(nap)(η6-p-cymene)] (3) were active against both Leishmania species. Complex [RuCl(ibu)(η6-p-cymene)] (2) has exhibited no activity. The IC50 values for the two active complexes were respectively 7.42 and 23.55 μM, for L. (L.) amazonensis, and 8.57 and 42.25 μM, for L. (L.) infantum. Based on the toxicological results and computational analysis, we proposed a correlation between the complexes and their activity. Our results suggest both complexation to ruthenium(II) and ligands structure are key elements to leishmanicidal activity. [ABSTRACT FROM AUTHOR]

The antimetabolite 5-fluorocytosine (5-FC) was used to form pharmaceutical cocrystals in order to modulate its poor physicochemical stability in humid environments, which leads to the irreversible incorporation of a water molecule at the structural level under storage conditions. The anhydrous form of 5-FC is a well-known fluorinated analog of cytosine with antifungal activity and it has become one of the most used medications for cancer treatment via the gene therapy approach. In this study, novel 5-FC cocrystals were obtained from the reaction of 5-FC with three nontoxic coformers: caffeine (CAF), p-aminobenzoic acid (PABA) and caprylic acid (CA). These cocrystals, namely 5FC–CAF, 5FC–PABA and 5FC–CA, were characterized by single-crystal and powder X-ray diffraction (SCXRD and PXRD), spectroscopic (FT-IR and FT-Raman) and thermal (thermogravimetric analysis, differential scanning calorimetry, and hot-stage microscopy) techniques. The physical stabilities of 5-FC and its cocrystals were evaluated in environments with high relative humidity and the equilibrium solubility was measured in a pH 1.2 buffer medium. These studies show that the prodrug 5-FC is able to form different homo and heterosynthons that lead to cocrystal formation. Additionally, the solubility profiles of the novel multicomponent solid forms were found to be similar to the API raw material, a BCS class I drug, exhibiting a high solubility profile. The hydration stabilities of 5-FC and its cocrystals were evaluated in humid environments to confirm the irreversible hydration of 5-FC in contrast with the absence of phase transitions in its cocrystal forms. In this way all 5-FC cocrystals reported herein maintained to a large degree the API solubility and do not undergo the hydration process or phase transition under extreme storage conditions, being more stable than the parent 5-FC. [ABSTRACT FROM AUTHOR]

Herein, we used thymine (HThy) as a ligand to form two new ruthenium(ii) complexes with formula [Ru(PPh3)2(Thy)(bipy)]PF6 (1) and [Ru(Thy)(bipy)(dppb)]PF6 (2). The complexes were characterized by spectroscopic, spectrometric and X-ray crystallography analyses. Complexes 1 and 2 can interact with ctDNA presenting binding constants, Kb, of 0.4 and 1.2 × 103 M−1, respectively. Their cytotoxic activities towards tumor cell lines (B16-F10, HepG2, K562 and HL-60) and non-tumor cells (PBMCs) were evaluated using the Alamar blue assay. Complex 1 exhibits high cytotoxicity against tumor cells, showing IC50 values of 0.01 and 1.81 μM against the HL-60 and HepG2 cell lines, respectively. Therefore, compound 1 can be considered as a promising antitumor metallodrug. [ABSTRACT FROM AUTHOR]

The 2-hydrazino­pyridine precursor has been widely used to prepare ligands of various kinds by condensation with carbonyl compounds. These types of ligands are suitable for synthesizing novel transition metal (II) complexes with inter­esting magnetic properties. In this context we have synthesized the ligand 1-(2-hy­droxy­phenyl-2-ethyl­idene)-2-(pyridin-2-yl)hydrazine (HL) which was used in the preparation of the mononuclear title complex, [Ni(C13H12N3O)(C13H13N3O)]NO3·0.5H2O. As a result of the presence of HL and L in the [{Ni(HL)(L)}]+ unit, the complex appears to be a supramolecular dimer composed of the Δ(−) and Λ(−) optical isomers, which are linked by strong hydrogen-bonds. As well as the dimer generated by two mononuclear [{Ni(HL)(L)}]+ cations, the asymmetric unit also contains two nitrate anions and one water mol­ecule. Each Ni atom is coordinated to two ligand mol­ecules by a nitro­gen atom of the pyridine ring, an imine nitro­gen atom and a phenolic oxygen atom of one of the ligand mol­ecules and a phenolate oxygen atom of the other organic mol­ecules. The environment around the cation is a distorted octa­hedron. The basal planes are defined by the two nitro­gen atoms of the pyridine rings and the two phenolic oxygen atoms of the ligand, the apical positions being occupied by the azomethine atoms. The O atoms of one of the nitrate ions are disordered over two sets of sites in a 0.745 (9):0.255 (9) ratio. In the crystal, the dimers are linked by numerous hydrogen bonds, forming a three-dimensional framework. [ABSTRACT FROM AUTHOR]

The aim of this work was the synthesis, characterization, and cytotoxicity evaluation of three new Ru(II) complexes with a general formula [Ru(Spy)(bipy)(P-P)]PF [Spy = pyridine-6-thiolate; bipy = 2,2′-bipyridine; P-P = 1,2-bis(diphenylphosphine)ethane (1); 1,3-bis(diphenylphosphine) propane (2); and 1,1′-bis(diphenylphosphino)ferrocene] (4). Complex (3) with the 1,4-bis(diphenylphosphine)butane ligand, already known from the literature, was also synthesized, to be better studied here. The cytotoxicities of the complexes toward two kinds of cancerous cells (K562 and S-180 cells) were evaluated and compared to normal cells (L-929 and PBMC) by MTT assay. The complex [Ru(Spy)(bipy)(dppb)]PF (3) was selected to study both the cellular and molecular mechanisms underlying its promising anticancer action in S-180 cells. The results obtained from this study indicated that complex (3) induces cell cycle arrest in the G0/G1 phase in S-180 cells associated with a decrease in the number of cells in S phase. After 24 and 48 h of exposure to complex (3), the cell viability decreased when compared to the negative control. Complex (3) does not appear to be involved in the DNA damage, but induced changes in the mitochondrial membrane potential in S-180 cells. Furthermore, there was also an increase in the gene expression of Bax, Caspase 9, and Tp53. According to our results, complex (3) induces cell apoptosis through p53/Bax-dependent intrinsic pathway and suppresses the expression of active antiapoptotic Bcl-2 protein. [ABSTRACT FROM AUTHOR]

Transition metal complexes containing dimethyl sulfoxide (DMSO) are important precursors in catalysis and metallodrugs. Understanding the solid-state supramolecular structure is crucial for predicting the properties and biological activity of the material. Several crystalline phases of DMSO-coordinated iridium anions with different cations, potassium (1 a) and n-butylammonium (1 b), were obtained and their structures determined by X-ray crystallography. Compound (1 a) is present in two solvatomorphic forms: α and β; the β form contains disordered solvent water. In addition, the structures exhibit different rotamers of the trans-[IrCl4(DMSO)2]− anion with the trans-DMSO ligands being oriented in anti and gauche conformations. In consideration of these various conformers, the effects of the crystallized solvent and intermolecular interactions on the conformational preferences of the anion are discussed. In addition, density functional theory calculations were used to investigate the energies of the anions in the different conformations. It was found that hydrogen bonds between water and the DMSO complex stabilize the gauche conformation which is the least stable form of the trans-DMSO complex. Consequently, by controlling the number of hydrogen-bond donors and acceptors and the amount of water, it may be possible to obtain different solvatomorphs of clinically significant metallodrugs. [ABSTRACT FROM AUTHOR]