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Drug–drug salts are a kind of pharmaceutical multicomponent solid in which the two co-existing components are active pharmaceutical ingredients (APIs) in their ionized forms. This novel approach has attracted great interest in the pharmaceutical industry since it not only allows concomitant formulations but also has proved potential to improve the pharmacokinetics of the involved APIs. This is especially interesting for those APIs that have relevant dose-dependent secondary effects, such as non-steroidal anti-inflammatory drugs (NSAIDs). In this work, six multidrug salts involving six different NSAIDs and the antibiotic ciprofloxacin are reported. The novel solids were synthesized using mechanochemical methods and comprehensively characterized in the solid state. Moreover, solubility and stability studies, as well as bacterial inhibition assays, were performed. Our results suggest that our drug–drug formulations enhanced the solubility of NSAIDs without affecting the antibiotic efficacy. [ABSTRACT FROM AUTHOR]

From the reaction of Co(II) hydroxy-carbonates and N-p-(R)-phenethyliminodiacetic acids (H2pheida, R = H and H2MOpheida, R = CH3O) two binary complexes have been obtained in aqueous media. The crystal pattern of [Co(pheida)(H2O)3]·1.5H2O (1) (monoclinic, space group C2/c) differs from the related non-hydrated crystal of [Co(MOpheida)(H2O)3] (2) (monoclinic, space group P21/c). Both Co(II) complexes display distorted octahedral geometry imposed by 3d7 electronic configuration. Our crystallographic results reveal that the metal chelates have a molecular structure and the used methoxy-substituent on the pheida skeleton yield different structural features. The iminodiacetic acid-arms [IDA] of pheida-like ligands adopt fac-NO2 conformation. For both chelators 1 and 2, single-point energy was calculated using restricted and/or unrestricted Hartree–Fock/BP/B3LYP functional. The analytical frequency, electronic absorption, and HOMO–LUMO energy gap were calculated using B3LYP functional with orbital basis set def2-SVP or def2-TZVP (for 2) along with the auxiliary basis set def2/J. The quantum chemical calculated geometry parameters are compared with their corresponding X-ray crystallographic data. The optical band gap (Eg) arises due to the electronic transitions. The direct and indirect band gap energy measured 3.26, 3.19 eV for 1 and 3.39, 3.35 eV for 2, respectively, reflecting their semi-conducting nature. Crystal structure for H2MOpheida acid also reported herein. [ABSTRACT FROM AUTHOR]

The stoichiometric reactions between Ni(II) hydroxy-carbonates and N-p-(R)-H2pheida derivatives (R = MeO or F for MOpheida or Fpheida, respectively) yield two binary compounds [Ni(MOpheida)(H2O)3] (1) and [Ni(Fpheida)(H2O)3] (2). The crystal of compounds 1 and 2 are iso-type; space group P21/c. Our crystallographic results revealed that both studied metal-chelates have molecular structure and the used p-R substituents on the pheida skeleton yield the same structural features. The IDA moiety of pheida-like ligands exhibit the fac-NO2 conformation (1 & 2). Crystal structure of H2Fpheida free acid have also been reported herein. [ABSTRACT FROM AUTHOR]

Eight Cu(II) complexes with N-(p-, m- or o-trifluoromethylbenzyl)iminodiacetate chelators (x-3F ligands) have been synthesized to promote C–F/H interligand interactions involving the F3C-group: {[Cu(μ2-p-3F)(H2O)]·3H2O]}n(1), [Cu(m-3F)(H2O)2] (2), [Cu(p-3F)(Him)(H2O)] (3), [Cu(m-3F)(Him)(H2O)] (4), [Cu(o-3F)(Him)(H2O)] (5), [Cu2(p-3F)2(H5Meim)2(H2O)2] (6), [Cu(m-3F)(H5Meim)(H2O)] (7), and [Cu(o-3F)(H5Meim)(H2O)] (8) [Him and H5Meim = imidazole and the “remote” tautomer 5-methylimidazole, respectively]. The compounds were studied by single-crystal X-ray diffraction, FT-IR, electronic spectra and coupled thermogravimetric + FT-IR methods. The conformation of the iminodiacetate chelating moiety (IDA group) isfac-NO + O(apical) in1andmer-NO2in2–8. Thefac-IDA conformation observed in1is related to its polymeric structure and the coordination of a O’-carboxylate donor, from an adjacent complex unit,transto the Cu–N(IDA) bond. Themer-IDA conformation in2is in agreement with similar compounds with an aqua ligandtransto the corresponding Cu–N(IDA) bond. As expected, the ternary complexes3–8feature amer-IDA conformation. Some of the studied complexes exhibit disorder in the –CF3group and C–H⋯F interligand interactions along with conventional N–H⋯O and O–H⋯O interactions. The thermal decomposition of all studied compounds under air flow produces variable amounts of trifluorotoluene. [ABSTRACT FROM AUTHOR]

The intrinsic acid-base properties of the hexa-2′-deoxynucleoside pentaphosphate, d(ApGpGpCpCpT) [=(A1⋅G2⋅G3⋅C4⋅C5⋅T6)=(HNPP)5−] have been determined by 1H NMR shift experiments. The p Ka values of the individual sites of the adenosine (A), guanosine (G), cytidine (C), and thymidine (T) residues were measured in water under single-strand conditions (i.e., 10 % D2O, 47 °C, I=0.1 M, NaClO4). These results quantify the release of H+ from the two (N7)H+ (G⋅G), the two (N3)H+ (C⋅C), and the (N1)H+ (A) units, as well as from the two (N1)H (G⋅G) and the (N3)H (T) sites. Based on measurements with 2′-deoxynucleosides at 25 °C and 47 °C, they were transferred to p Ka values valid in water at 25 °C and I=0.1 M. Intramolecular stacks between the nucleobases A1 and G2 as well as most likely also between G2 and G3 are formed. For HNPP three p Ka clusters occur, that is those encompassing the p Ka values of 2.44, 2.97, and 3.71 of G2(N7)H+, G3(N7)H+, and A1(N1)H+, respectively, with overlapping buffer regions. The tautomer populations were estimated, giving for the release of a single proton from five-fold protonated H5(HNPP)±, the tautomers (G2)N7, (G3)N7, and (A1)N1 with formation degrees of about 74, 22, and 4 %, respectively. Tautomer distributions reveal pathways for proton-donating as well as for proton-accepting reactions both being expected to be fast and to occur practically at no 'cost'. The eight p Ka values for H5(HNPP)± are compared with data for nucleosides and nucleotides, revealing that the nucleoside residues are in part affected very differently by their neighbors. In addition, the intrinsic acidity constants for the RNA derivative r(A1⋅G2⋅G3⋅ C4⋅C5⋅U6), where U=uridine, were calculated. Finally, the effect of metal ions on the p Ka values of nucleobase sites is briefly discussed because in this way deprotonation reactions can easily be shifted to the physiological pH range. [ABSTRACT FROM AUTHOR]

This work deals with the preparation of pyridine-3-carbohydrazide (isoniazid, inh) cocrystals with two α-hydroxycarboxylic acids. The interaction of glycolic acid (H2ga) or d,l-mandelic acid (H2ma) resulted in the formation of cocrystals or salts of composition (inh)·(H2ga) (1) and [Hinh]+[Hma]–·(H2ma) (2) when reacted with isoniazid. An N′-(propan-2-ylidene)isonicotinic hydrazide hemihydrate, (pinh)·1/2(H2O) (3), was also prepared by condensation of isoniazid with acetone in the presence of glycolic acid. These prepared compounds were well characterized by elemental analysis, and spectroscopic methods, and their three-dimensional molecular structure was determined by single crystal X-ray crystallography. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems. Finally, Hirshfeld surface analysis and Density-functional theory (DFT) calculations (including NCIplot and QTAIM analyses) have been performed to further characterize and rationalize the non-covalent interactions. [ABSTRACT FROM AUTHOR]

The synthetic nucleoside acyclovir is considered an outstanding model of the natural nucleoside guanosine. With the purpose of deepening on the influence and nature of non-covalent interactions regarding molecular recognition patterns, three novel Cu(II) complexes, involving acyclovir (acv) and the ligand receptor N-(2-hydroxyethyl)ethylenediamine (hen), have been synthesized and thoroughly characterized. The three novel compounds introduce none, one or two acyclovir molecules, respectively. Molecular recognition has been evaluated using single crystal X-ray diffraction. Furthermore, theoretical calculations and other physical methods such as thermogravimetric analysis, infrared and UV-Vis spectroscopy, electron paramagnetic resonance and magnetic measurements have been used. Theoretical calculations are in line with experimental results, supporting the relevance of the [metal-N7(acv) + H-bond] molecular recognition pattern. It was also shown that (hen)O-H group is used as preferred H-donor when it is found within the basal coordination plane, since the higher polarity of the terminal (hen)O-H versus the N-H group favours its implication. Otherwise, when (hen)O-H occupies the distal coordination site, (hen)N-H groups can take over. [ABSTRACT FROM AUTHOR]

We synthesized and studied the polymeric compound {[Cu2(µ4-EDTA)(Him)2] 2H2O}n (1). The single-crystal structure is reported along with an in depth characterization of its thermal stability (TGA), spectral properties (FT-IR, Vis-UV and RSE), and magnetic behavior. The crystal consists of infinite 2D-networks built by centrosymmetric dinuclear motifs, constructed by means of a bridging anti,syn-carboxylate group from each asymmetric unit. Each layer guides Him ligands toward their external faces. They are connected by intermolecular (Him)N-H···O(carboxylate) bonds and antiparallel π–π stacking between symmetry related pairs of Him ligands, and then pillared in a 3D-network with parallel channels, where disordered water molecules are guested. About half of the labile water is lost from these channels over a wide temperature range (r.t. to 210 °C) before the other one, most strongly retained by the cooperating action of (water)O1-H(1A)···O(carboxylate) and (water) O1-H(1B)···π(Him) interactions. The latter is lost when organic ligands start to burn. ESR spectra and magnetic measurements indicated that symmetry related Cu(II) centers connected by the bridging carboxylate groups behave magnetically not equivalently, enabling an exchange interaction larger than their individual Zeeman energies. [ABSTRACT FROM AUTHOR]