Potent acetylcholinesterase inhibitors: Synthesis, biological assay and docking study of nitro acridone derivatives.

The reaction of o-halobenzoic acid with aniline derivatives and their subsequent cyclization reaction yielded the acridone derivatives. The series of nitro acridone derivatives were prepared by Ullmann condensation in presence of copper as catalyst and were characterized by FTIR, (1)H, (13)C NMR and mass spectra. The structure of 5-nitro-(2-phenyl amino) benzoic acid (4) was confirmed by X-ray crystallography and was found to crystallize in P21/c space group. The in vitro efficacy of the compounds for their acetylcholinesterase (AChE) and antimicrobial inhibitory activities have been evaluated against the standard drugs Ampicillin and Gentamicin against Gram positive and Gram negative bacteria. 1,7-Dinitroacridone was found to be the most potent AChE inhibitor (IC50=0.22µM). Moreover, the compounds have been screened for their antioxidant activity using the DPPH assay. Also, docking study results were found to be in good agreement with the results obtained through in vitro experiments. The docking study further predicted possible binding conformation.

Synthesis, structure, and spectral and electrochemical properties of chromium(III) tris-(8-hydroxyquinolinate).

The kinetically inert chromium(III) tris-(8-hydroxyquinolinate), Crq3, has been synthesized, crystallized from 90% methanol-water, and characterized by MALDI-TOF mass spectrometry, thermogravimetry, FTIR, NMR spectroscopy, and X-ray powder diffraction. It is formed as a methanol solvate, but the solvent can be removed by heating. Large paramagnetic shifts and spectral broadening in (1)H NMR spectra indicate electron delocalization between the metal and the ligand. DFT calculations show it is present as the meridional isomer, with the HOMO largely based on one of the metal 3d orbitals and the LUMO essentially localized on the ligands. Cyclic voltammetry (CV) in acetonitrile solutions shows four oxidation peaks and two, less intense reduction waves on the first scan. The HOMO energy determined from the first oxidation peak is fairly close to that obtained by DFT, in agreement with this being mainly metal based. Although the number of peaks decreases on subsequent CV scans, the complex shows markedly enhanced electrochemical stability compared with aluminium(III) tris-(8-hydroxyquinolinate). Solution UV/visible absorption and solid diffuse reflectance spectra have a weak, long wavelength band, assigned to the metal based d-d transition, in addition to the normal, ligand based bands seen in metal quinolates. The energy of the lowest energy band is identical to the HOMO-LUMO separation obtained by cyclic voltammetry, in agreement with the above description. The compound is only weakly luminescent, in contrast to many other metal quinolates, due to the lowest energy transition being metal rather than ligand based. The potential of this compound as an electron transporting/hole blocking layer in optoelectronic devices is indicated.

Slow magnetic relaxation mechanisms in erbium SIMs.

The magnetic properties of two similar Er(3+) complexes have been investigated. [Er(tpm)3(bipy)] (Htpm = 1,1,1-trifluoro-5,5-dimethyl-2,4-hexanedione and bipy = 2,2'-bipyridine) displays thermally activated slow relaxation of magnetisation under a zero direct-current (DC) field. Under an applied HDC field of 1000 G, [Er(tpm)3(bipy)] exhibits two thermally activated processes with energy barriers of 9 and 40 K, while [Er(tfa)3(bipy)] (Htfa = 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione) shows only one activated process with a barrier of 15 K. Both compounds are luminescent in the solid state, emitting in the near IR region.

Active layer solution-processed NIR-OLEDs based on ternary erbium(III) complexes with 1,1,1-trifluoro-2,4-pentanedione and different N,N-donors.

Using a fluorinated 1,1,1-trifluoro-2,4-pentanedione (Htfac) ligand and either 2,2'-bipyridine (bipy), bathophenanthroline (bath) or 5-nitro-1,10-phenanthroline (5NO2phen) as an ancillary ligand, three new ternary erbium(iii) octacoordinated complexes have been synthesized. The single crystal structures of the new complexes (namely [Er(tfac)3(bipy)], [Er(tfac)3(bath)] and [Er(tfac)3(5NO2phen)]) have been determined and their properties have been investigated by Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy and thermodynamic analysis. After ligand-mediated excitation of these complexes in the UV, they all show the characteristic near-infrared (NIR) luminescence of the corresponding Er(3+) ion at 1532 nm. The same emission in the C-band transmission window can also be obtained from the solution-processed organic light-emitting diodes (OLEDs) with structure: glass/ITO/PEDOT:PSS/[Er(tfac)3(N,N-donor)]/Ca/Al. In spite of the fact that the photoluminescence intensity of [Er(tfac)3(5NO2phen)] is stronger than those of [Er(tfac)3(bipy)] and [Er(tfac)3(bath)], the best electroluminescence results correspond to the OLED based on the [Er(tfac)3(bath)] complex, as a consequence of the superior electron transport capabilities of bathophenanthroline.

A thermodynamic based approach on the investigation of a diflunisal pharmaceutical co-crystal with improved intrinsic dissolution rate.

A thermodynamic based approach is used to investigate diflunisal+nicotinamide binary and solution mixtures. A 2:1 co-crystal could be prepared by liquid assisted ball mill grinding and by solution crystallization from ethanol. The diflunisal+nicotinamide+ethanol ternary phase diagram points out conditions for co-crystal scaling-up. From the diflunisal+nicotinamide binary phase diagram, besides identification of the co-crystal stoichiometry, two additional useful binary compositions, eutectic mixtures, were characterized. From a solution enthalpy based approach, the enthalpic stabilization of the co-crystal relative to the pure solid components is quantified. Intrinsic dissolution rate, IDR, in test conditions consistent with USP requirements, including those referred in the diflunisal tablet monograph, were carried out, indicating that the co-crystal improves diflunisal IDR by about 20%. The systematic study of diflunisal+nicotinamide mixtures presented in this work is of particular interest due to the relevance of diflunisal, both as a non-steroidal anti-inflammatory drug and also due to the potentiality of orally administrated diflunisal in familial amyloid polyneuropathy.

Study of Nα-benzoyl-L-argininate ethyl ester chloride, a model compound for poly(ester amide) precursors: x-ray diffraction, infrared and Raman spectroscopies, and quantum chemistry calculations.

Poly(ester amide)s (PEAs) are lacking in structural and spectroscopic information. This paper reports a structural and spectroscopic characterization of N(α)-benzoyl-L-argininate ethyl ester chloride (BAEEH(+)·Cl(-)), an important amino acid derivative and an adequate PEAs' model compound. Crystals of BAEEH(+)·Cl(-) obtained by slow evaporation in an ethanol∕water mixture were studied by different complementary techniques. X-ray analysis shows that BAEEH(+)·Cl(-) crystallizes in the chiral space group P2(1). There are two symmetry independent cations (and anions) in the unit cell. The two cations have different conformations: in one of them, the angle between the least-squares planes of the phenyl ring and the guanidyl group is 5.1(2)°, and in the other the corresponding angle is 13.3(2)°. There is an extensive network of H-bonds that assembles the ions in layers parallel to the ab plane. Experimental FT-IR and Raman spectra of BAEEH(+)·Cl(-) were recorded at room temperature in the 3750-600 cm(-1) and 3380-100 cm(-1) regions, respectively, and fully assigned. Both structural and spectroscopic analysis were supported by quantum chemistry calculations based on different models (in vacuo and solid-state DFT simulations).

Crystal and molecular structure of DL-serine hydrochloride studied by X-ray diffraction, low-temperature Fourier transform infrared spectroscopy and DFT(B3LYP) calculations.

The structure of dl-serine.HCl was studied by three complementary techniques. Experimental Fourier transform infrared (FT-IR) spectra of pure NH/OH polycrystalline dl-serine.HCl [HO-CH2-CH(NH3+)-COOH.Cl(-)] and the respective deuterated derivatives [ND/ODAlcohol/Acid (<10% and ca. 60% D)] were recorded in the region 4000-400 cm(-1) in the temperature range 300-10 K and interpreted. The assignments were confirmed by comparison with the vibrational spectra of crystalline dl- and l-serine zwitterions [HO-CH 2-CH(NH3+)-COO(-)]. Further insight into the structure of the title compound was provided by theoretical DFT(B3LYP)/6-311++G(d,p) calculations of the infrared spectra and energies of 13 different conformers. Potential energy distributions resulting from normal co-ordinate analysis were calculated for the most stable conformer ( I) in its hydrogenated and deuterated modification. Frequencies of several vibrational modes were used in the estimation of enthalpies of individual H-bonds present in the crystal, using empirical correlations between enthalpy and the frequency shift that occurs as a result of the establishment of the H-bonds. X-ray crystallography data for dl-serine.HCl were recorded for the first time and, together with the experimental vibrational spectra and the theoretical calculations, allowed a detailed characterization of its molecular structure.

Crystal and molecular structure of 4,6-bis(nitroimino)-1,3,5-triazinan-2-one: theoretical and X-ray studies.

This paper provides an overview of recent progress on structural data on the title compound. Theoretical work based on quantum mechanical calculations was performed to gain some understanding on the heterocyclic tautomerism potentially exhibited by the compound. The computational studies encompassed a wide range of tautomers/conformers, allowing the determination of the most probable molecular structure. In the gas phase, the nitroimine tautomers are computed to be substantially more stable than the nitramine tautomers. Among three plausible nitroimine forms, special attention was given to 4,6-bis(nitroimino)-1,3,5-triazinan-2-one, whose crystal structure was unequivocally solved by X-ray diffraction. The crystals are orthorhombic, space group Pnma with a = 6.187(2)A, b = 13.252(5)A, c = 8.802(4)A, and Z = 4. The structure was solved by direct methods and refined to a final R = 0.0326. The molecule has an approximate mirror plane relating the two symmetry related halves. The nitroimine groups are positioned in a syn-syn conformation. The least-squares (LS) plane of the heterocyclic ring and the nitroimine ([double bond]N-NO2) substituent LS plane make an angle of 10.05(11) degrees. The crystal structure is held together via hydrogen bonds that assemble the molecules in chains running along the b-axis. Every H-atom is involved in bifurcated hydrogen bonds.

6beta-Azido-7alpha-hydroxy-17-oxo-5alpha-androstan-3beta-yl acetate.

In the title compound, C21H31N3O4, a potential inhibitor of aromatase, all rings are fused trans. Rings A, B and C have chair conformations which are slightly flattened. Ring D has a 14alpha-envelope conformation. The steroid nucleus has a small twist, as shown by the C19-C10...C13-C18 torsion angle of 6.6 (2) degrees. Ab initio calculations of the equilibrium geometry of the molecule reproduce this small twist, which appears to be due to the steric effect of the 6beta-azide substituent rather than to packing effects.

17-Oxo-5 alpha-androst-6-en-3 beta-yl acetate.

In the title compound, C(21)H(30)O(3), a potential inhibitor of aromatase, all rings are fused trans. Rings A and C have chair conformations which are slightly flattened, whereas the conformation of ring B is close to a half-chair. Ring D has a 14 alpha-envelope conformation. The steroid nucleus has a small twist, as shown by the C19-C10...C13-C18 (steroid numbering) torsion angle of -6.9 (3) degrees. Ab initio calculations of the equilibrium geometry of the molecule reproduce this small twist, which appears to be due to the conformation of ring B rather than to packing effects.