Metal Complexes of New Bioactive Pyrazolone Phenylhydrazones; Crystal Structure of 4-Acetyl-3-methyl-1-phenyl-2-pyrazoline-5-one phenylhydrazone Ampp-Ph.

The condensation reaction of phenylhydrazine and dinitrophenylhydrazine with 4-acetyl and 4-benzoyl pyrazolone precipitated air-stable acetyldinitrophenylhydrazone Ampp-Dh, benzoylphenylhydrazone Bmpp-Ph and benzoyldinitrophenylhydrazone Bmpp-Dh in their keto imine form; a study inspired by the burning interest for the development of new bioactive materials with novel properties that may become alternative therapeutic agents. Elemental analysis, FTIR, ¹H, and (13)C NMR, and mass spectroscopy have been used to justify their proposed chemical structures, which were in agreement with the single crystal structure of Bmpp-Dh earlier reported according to X-ray crystallography. The single crystal structure of 4-acetyl-3-methyl-1-phenyl--pyrazoline-5-one phenylhydrazone Ampp-Ph, which crystallizes in a triclinic crystal system with a P-1 (No. 2) space group is presented. Octahedral Mn(II), Ni(II), Co(II), and Cu(II) complexes of these respective ligands with two molecules each of the bidentate Schiff base, coordinating to the metal ion through the azomethine nitrogen C=N and the keto oxygen C=O, which were afforded by the reaction of aqueous solutions of the corresponding metal salts with the ligands are also reported. Their identity and proposed structures were according to elemental analysis, FTIR spectroscopy, UV-VIS spectrophotometry (electronic spectra) and Bohr magnetic moments, as well as thermogravimetric analysis (TGA) results. A look at the antibacterial and antioxidant activities of synthesized compounds using the methods of the disc diffusion against some selected bacterial isolates and 1,1-diphenyl-2-picryl-hydrazil (DPPH) respectively, showed biological activities in relation to employed standard medicinal drugs.

Clathrates of TETROL: Further Aspects of the Selective Inclusion of Methylcyclohexanones in Their Energetically Unfavorable Axial Methyl Conformations.

(+)-(2R,3R)-1,1,4,4-Tetraphenylbutane-1,2,3,4-tetraol (TETROL) functions as a highly efficient host for the inclusion of cyclohexanone and 2-, 3-, and 4-methylcyclohexanone, all with 1:1 host/guest ratios. Most extraordinarily, the 3- and 4-methyl isomers are uniquely included in their higher energy axial methyl conformations rather than as their more energetically favorable equatorial analogues. In contrast, 2-methylcyclohexanone is included more conventionally in the equatorial methyl conformation. During recrystallization of TETROL from racemic 2- and 3-methylcyclohexanone, some preference is shown by the host for the (R)-enantiomer. In the latter case, this is attributed to a much stronger H-bond between a hydroxyl group of TETROL and the carbonyl group of the (R)-enantiomer (O···O 2.621(2) Å) compared with a significantly weaker H-bond to the (S)-enantiomer (3.125(8) Å). In the former instance, hydrogen-bond strengths to both enantiomers are similar, but the (R)-enantiomer engages in three (guest)CH···π(host) and three (guest)H···Car(host) contacts, whereas fewer interactions of these types are observed for the (S)-enantiomer. Calculations of geometries of the guest cyclohexanones were determined at the MP2/6-311++G(2df,2p) level and compared with those obtained at the G3(MP2) level. Finally, an interesting correlation between crystal packing indices for the three methylcyclohexanone clathrates and their respective desolvation onset temperatures was identified.

rac-Hy-droxy-isovaleric acid.

The title compound (systematic name: rac-2-hydroxy-3-methylbutanoic acid), C5H10O3, is the constitutional isomer of α-hy-droxy-butanoic acid. In the crystal, hydrogen bonds involving the alcoholic hydroxyl group give rise to centrosymmetric dimers that are extended to sheets perpendicular to the crystallographic c axis.

Copper(II)-photocatalyzed Hydrocarboxylation of Schiff bases with CO2: antimicrobial evaluation and in silico studies of Schiff bases and unnatural α-amino acids.

We synthesized and characterized two copper(II) complexes: [CuL2Cl]Cl and [CuL'2Cl]Cl, where L = 2,2'-bipyridine and L' = 4,4'-dimethyl-2,2'-bipyridine. We evaluated their photocatalytic hydrocarboxylation properties on a series of synthesized Schiff bases (SBs): (E)-1-(4-((5-bromo-2-hydroxybenzylidene)amino)phenyl)ethanone (SB1), (E)-N-(4-(dimethylamino)benzylidene)benzo[d]thiazol-2-amine (SB2), (E)-4-Bromo-2-((thiazol-2-ylimino)methyl)phenol (SB3), and (E)-4-((5-bromo-2-hydroxybenzylidene)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (SB4). Under mild photocatalytic reaction conditions (room temperature, 1 atm CO2, 30-watt Blue LED light), the derivatives of α-amino acids UAA1-4 were obtained with yields ranging from 5% to 44%. Experimental results demonstrated that [CuL2Cl]Cl exhibited superior photocatalytic efficiency compared to [CuL'2Cl]Cl, attributed to favourable electronic properties. In silico studies revealed strong binding strengths with E. faecalis DHFR (4M7U) for docked Schiff bases (SB) and unnatural α-amino acids (UAAs). In vitro studies further demonstrated significant antimicrobial and antifungal activity for SB2, SB3, and SB4, while none of the synthesized UAAs exhibited such properties, primarily due to the electronic and binding properties of these molecules.Communicated by Ramaswamy H. Sarma.

Synthesis, crystal structure and in-silico evaluation of arylsulfonamide Schiff bases for potential activity against colon cancer.

This report presents a comprehensive investigation into the synthesis and characterization of Schiff base compounds derived from benzenesulfonamide. The synthesis process, involved the reaction between N-cycloamino-2-sulfanilamide and various substituted o-salicylaldehydes, resulted in a set of compounds that were subjected to rigorous characterization using advanced spectral techniques, including 1H NMR, 13C NMR and FT-IR spectroscopy, and single-crystal X-ray diffraction. Furthermore, an in-depth assessment of the synthesized compounds was conducted through Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis, in conjunction with docking studies, to elucidate their pharmacokinetic profiles and potential. Impressively, the ADMET analysis showcased encouraging drug-likeness properties of the newly synthesized Schiff bases. These computational findings were substantiated by molecular properties derived from density functional theory (DFT) calculations using the B3LYP/6-31G* method within the Jaguar Module of Schrödinger 2023-2 from Maestro (Schrodinger LLC, New York, USA). The exploration of frontier molecular orbitals (HOMO and LUMO) enabled the computation of global reactivity descriptors (GRDs), encompassing charge separation (Egap) and global softness (S). Notably, within this analysis, one Schiff base, namely, 4-bromo-2-{N-[2-(pyrrolidine-1-sulfonyl)phenyl]carboximidoyl}phenol, 20, emerged with the smallest charge separation (ΔEgap = 3.5780 eV), signifying heightened potential for biological properties. Conversely, 4-bromo-2-{N-[2-(piperidine-1-sulfonyl)phenyl]carboximidoyl}phenol, 17, exhibited the largest charge separation (ΔEgap = 4.9242 eV), implying a relatively lower propensity for biological activity. Moreover, the synthesized Schiff bases displayed remarkeable inhibition of tankyrase poly(ADP-ribose) polymerase enzymes, integral in colon cancer, surpassing the efficacy of a standard drug used for the same purpose. Additionally, their bioavailability scores aligned closely with established medications such as trifluridine and 5-fluorouracil. The exploration of molecular electrostatic potential through colour mapping delved into the electronic behaviour and reactivity tendencies intrinsic to this diverse range of molecules.

The formation of 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepine from 1,2-diaminobenzene in the presence of acetone.

In an attempt to synthesize a 2-substituted benzimidazole from the reaction of o-phenylenediamine and isophthalic acid in the presence of acetone and ethanol under microwave irradiation, a salt of the isophthalate ion and 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepin-5-ium ion was obtained. The condensation of two moles of acetone with the amine groups resulted in the formation of the benzodiazepine which crystallized as an iminium cation forming a salt with the isophthalate anion. The formation of benzodiazepine was also confirmed by performing the reaction of o-phenylenediamine with excess acetone in ethanol under conventional heating conditions. The compounds were characterized by NMR, FTIR, HRMS and microanalysis as well as X-ray crystallography. The reaction mechanism leading to the formation of benzodiazepine is also discussed.

2,4-Dichloro-benzyl 2-meth-oxy-benzoate.

In the title compound, C15H12Cl2O3, the aromatic rings make a dihedral angle of 10.78 (4)°. In the molecule, there is a short C-H⋯O contact. In the crystal, C-H⋯O contacts connect the mol-ecules into C(7)C(8) chains along the b axis. The shortest inter-centroid distance between two benzoic acid aromatic systems is 3.7416 (8) Å.

2-(4-Chloro-phen-yl)-2-oxoethyl naphthalene-1-carboxyl-ate.

In the title compound, C19H13ClO3, an ester of 1-naphthoic acid with an aromatic alcohol, the least-squares planes defined by the C atoms of the respective aromatic systems enclose an angle of 77.16 (3)°. In the crystal, C-H⋯O contacts connect the mol-ecules into undulating sheets parallel to the bc plane.

2-(4-Bromo-phen-yl)-2-oxoethyl naphthalene-1-carboxyl-ate.

In the title compound, C19H13BrO3, an ester of 1-naphthoic acid with an aromatic alcohol, the least-squares planes defined by the C atoms of the respective aromatic systems enclose an angle of 77.20 (5)°. In the crystal, C-H⋯O contacts connect the mol-ecules into undulating sheets parallel (100).

[1,1'-Bi-cyclo-hexa-ne]-1,1'-diol.

The title compound, C12H22O2, is a symmetric diol derived from the pinacol coupling of cyclo-hexa-none. The asymmetric unit contains three complete mol-ecules. The cyclo-hexane moieties adopt chair conformations. Cooperative hydrogen bonding connects the individual mol-ecules to infinite chains propagating along the crystallographic a-axis direction.

4-{[2-(2,4-Dinitro-phen-yl)hydrazinyl-idene](phen-yl)meth-yl}-5-methyl-2-phenyl-1H-pyrazol-3(2H)-one ethanol monosolvate.

In the title compound, C23H18N6O5·C2H6O, all three benzene rings lie in an approximate plane [maximum deviation = 0.2688 (16) Å] that makes an angle of 53.56 (3)° with the plane of the pyrazolone ring. Intra-molecular N-H⋯O hydrogen bonds occur. In the crystal, the ethanol solvent mol-ecule links adjacent mol-ecules through N-H⋯O-H⋯O hydrogen bonds, leading to an infinite chain along the c-axis direction. The ethyl group of the ethanol solvent mol-ecule is disordered over two set of sites in a 0.762 (5):0.238 (5) ratio.

(2-Ethyl-2-oxazoline-κN)bis(N-ethyl-N-phenyl-dithio-carbamato-κ(2)S,S')cadmium.

In the title compound, [Cd(C(9)H(10)NS(2))(2)(C(5)H(9)NO)], the Cd(II) atom is five-coordinated in a distorted square-pyramidal geometry by four S atoms from two chelating N-ethyl-N-phenyl dithio-carbamate ligands and one N atom from a 2-ethyl-2-oxazoline ligand. Inter-molecular C-H⋯π inter-actions are observed in the crystal structure.

(E)-1-[2-(Methyl-sulfan-yl)phen-yl]-2-({(E)-2-[2-(methyl-sulfan-yl)phen-yl]hydrazinyl-idene}(nitro)-meth-yl)diazene.

In the title compound, C(15)H(15)N(5)O(2)S(2), the phenyl rings make dihedral angles of 4.03 (4) and 9.77 (5)° with the plane defined by the central N-N-C-N-N atoms (r.m.s. deviation = 0.010 Å). The C-S-C-C torsion angles of the methyl-sulfanyl groups with their respective phenyl rings are -7.47 (13) and -72.07 (13)°. The shortest centroid-centroid distance of 3.707 Šoccurs between the two π-systems N-N-C-N-N and the benzene ring in the diazene 1-position. The H atom bound to the N atom is involved in intra-molecular N-H⋯N and N-H⋯S contacts, while the nitro O atoms are involved in inter-molecular C-H⋯O contacts.

2-({[4-(1,3-Benzothia-zol-2-yl)phen-yl]amino}methyl)-phenol.

In the title compound, C(20)H(16)N(2)OS, the aniline substituent essentially coplanar with the benzothia-zole moiety (with an r.m.s. deviation of all fitted non-H atoms of 0.0612 Å). The phenol group is almost perpendic-ular to the benzothia-zolylaniline group, with an inter-planar angle of 88.36 (2)°. In the crystal, mol-ecules aggregate as centrosymmetric dimers by pairs of O-H⋯N hydrogen bonds. C-H⋯O contacts and N-H⋯π(arene) inter-actions also occur.

Bis(4-benzoyl-3-methyl-1-phenyl-1H-pyrazol-5-olato-κ(2)O,O')bis-(ethanol-κO)cobalt(II).

The title compound, [Co(C(17)H(13)N(2)O(2))(2)(C(2)H(5)OH)(2)], is a Co(II) complex with two 4-benzoyl-3-methyl-1-phenyl-1H-pyrazol-5-olate (BMPP) ligands and two coordinating ethanol mol-ecules. In the asymmetric unit, there are two half mol-ecules, with the Co(II) atoms located on inversion centres. The two cobalt complexes have slightly different geometries and in one, the ethyl group of the ethanol is disordered over two sets of sites [occupancy ratio 0.757 (7):0.243 (7)]. Each BMPP ligand is deprotonated with the negative charge delocalized. The hy-droxy group of each ethanol mol-ecule forms hydrogen bonds with a pyrazole N atom in an adjacent BMPP ligand. Weaker C-H⋯O and C-H⋯N inter-actions link the mol-ecules into a three-dimensional structure.

1,5-Bis(2-methyl-phen-yl)-3-nitro-formazan.

In the title compound, C(15)H(15)N(5)O(2), the nitro O atoms are disordered over two sets of sites with an occupancy ratio of 0.75 (4):0.25 (4). Amine-imine tautomerism is observed in the formazan group. This was evident from the similar C-N bond distances in the formazan [1.319 (2) and 1.332 (3) Å], as well as the distribution of the imine proton in the Fourier difference map which refined to a 0.53 (3):0.47 (3) ratio. C-H⋯O and π-π inter-actions [centroid-centroid distances = 3.4813 (1) and 3.3976 (1) Å] are observed in the crystal packing.

Ethyl (Z)-3-(4-methyl-anilino)-2-[(4-methyl-phen-yl)carbamo-yl]prop-2-enoate.

The title compound, C(20)H(22)N(2)O(3), is a secondary amine featuring an amide and an ester functionality in connection with a Michael system. The conformation about the C=C bond is E. Intra-molecular N-H⋯O hydrogen bonds occur. In the crystal, C-H⋯O contacts connect the mol-ecules into chains along the b-axis direction.

Methyl 2-[(2-methyl-phen-oxy)meth-yl]benzoate.

In the title methyl-benzoate compound, C(16)H(16)O(3), the mol-ecule is essentially planar (r.m.s. of all fitted non-H atoms = 0.0370 Å); the dihedral angle between the phenyl rings is 2.30 (7)°. Apart from a C-H⋯π inter-action, no marked inter-molecular contacts are obvious.

Diethyl 2,6-dimethyl-4-[5-(4-methyl-phen-yl)-1H-pyrazol-4-yl]-1,4-dihydro-pyridine-3,5-dicarboxyl-ate.

In the title compound, C23H27N3O4, the dihydro-pyridine ring adopts a (1,4)B conformation. Intra-molecular C-H⋯O contacts occur. In the crystal, N-H⋯O and N-H⋯N hydrogen bonds and C-H⋯N contacts connect the mol-ecules into strands along the a-axis direction.

4-Meth-oxy-4-methyl-6-phenyl-1,3-diazinane-2-thione.

In the title pyrimidine derivative, C12H16N2OS, the tetra-hydro-pyrimidine ring adopts an envelope conformation with the C atom of the methyl-ene -CH2- group as the flap. In the crystal, N-H⋯O and N-H⋯S hydrogen bonds connect mol-ecules into undulating sheets perpendicular to the a axis.