Bis(thio)carbohydrazone Luminogens with AIEE and ACQ Features and Their In Silico Investigations with SARS-CoV-2.

Herein, we report two novel multidentate luminogen proligands bis(3,5-diiodosalicylidene) carbohydrazone (H4L1) and bis(3,5-diiodosalicylidene) thiocarbohydrazone (H4L2), which are suitable candidates for biomedical applications. Though the thiocarbohydrazone H4L2 shows aggregation caused quenching (ACQ), the carbohydrazone H4L1 exhibits stronger fluorescence due to aggregation induced emission enhancement (AIEE). Molecular docking studies of H4L1 and H4L2 along with four similar (thio)carbohydrazones with the active sites of SARS-CoV-2 main protease 3CLpro reveals that the thiocarbohydrazones, in general, are showing better propensity compared to their oxygen analogues. Both the thiocarbohydrazones and the carbohydrazones, however, exhibit better binding potential at the active sites than that of some of the repurposed drugs such as chloroquine, hydroxychloroquine, lopinavir, ritonavir, darunavir and remdesivir. Also, the carbohydrazone H4L1 can be a better bioprobe compared to H4L2 as the former is found to have better binding potential with SARS-CoV-2 spike glycoprotein along with AIEE feature.

Metal based biologically active compounds: Design, synthesis, DNA binding and antidiabetic activity of 6-methyl-3-formyl chromone derived hydrazones and their metal (II) complexes.

Two chromone hydrazone ligands HL1 and HL2 were synthesized and characterized by elemental analyses, IR, 1H NMR &13C NMR, electronic absorption and mass spectra. The reactions of the chromone hydrazones with transition metals such as Ni, Cu, and Zn (II) salts of acetate afforded mononuclear metal complexes. Characterization and structure elucidation of the prepared chromone hydrazone metal (II) complexes were done by elemental, IR, electronic, EPR spectra and thermo gravimetric analyses as well as conductivity and magnetic susceptibility measurements. The spectroscopic data showed that the ligand acts as a mono basic bidentate with coordination sites are azomethine nitrogen and hydrazonic oxygen, and they exhibited distorted geometry. The biological studies involved antidiabetic activity i.e. enzyme inhibition of α-amylase and α-glucosidase, Calf Thymus - DNA (CT-DNA) interaction and molecular docking. Potential capacity of synthesized compounds to inhibit the α-amylase and α-glucosidase activity was assayed whereas DNA interaction studies were carried out with the help UV-Vis absorption titration and viscosity method. The docking studies of chromone hydrazones show that they are minor groove binders. Complexes were found to be good DNA - intercalates. Chromone hydrazones and its transition metal complexes have shown comparable antidiabetic activity with a standard drug acarbose.

(1-{(E)-[Phen-yl(pyridin-2-yl-κN)methyl-idene]amino-κN}pyrrolidin-2-one-κO)bis-(thio-cyanato-κN)copper(II).

The Cu(II) atom in the title compound, [Cu(NCS)(2)(C(16)H(15)N(3)O)], is bonded to the N atoms of two thio-cyanate ions, and is N,N'-chelated by the Schiff base ligand. The four N atoms surround the metal atom to form a distorted square; the square environment is distorted towards a square pyramid by a long Cu⋯O inter-action. In the crystal, two C atoms of the pyrrolidin-2-one ring are disordered over two positions in a 1:1 ratio.

catena-Poly[[[{1-[(E)-phenyl(pyridin-2-yl-κN)methylidene]semicarbazidato-κ(2)N(1),O}copper(II)]-µ-dicyanamido-κ(2)N(1):N(5)] monohydrate].

The Cu(II) atoms in the title coordination polymer, {[Cu(C(13)H(11)N(4)O)(C(2)N(3))]·H(2)O}(n), are N,N',O-chelated by the deprotonated Schiff base ligands, and adjacent metal atoms are bridged by the dicyanamide ions, generating a polymeric chain that propagates along the b axis. The two independent metal atoms show a square-pyramidal N(4)O coordination. The two independent water mol-ecules are disordered over two positions; each water mol-ecule is a hydrogen-bond donor to a carbonyl O atom. Weak N-H⋯N hydrogen bonding is also observed.

(Cyanato-κN){1-[(E)-phen-yl(pyridin-2-yl-κN)methyl-idene]semicarbazidato-κ(2)N(1),O}copper(II).

The Cu(II) atom in the title compound, [Cu(C(13)H(11)N(4)O)(NCO)], is N,N',O-chelated by the mono-deprotonated Schiff base ligand and it is also covalently bonded to the nitro-gen end of the cyanate ion. The Cu(II) atom shows a square-planar coordination that is distorted towards square-pyramidal owing to an inter-molecular Cu⋯N(cyanate) inter-action [2.623 (2) Å], which gives a centrosymmetric dimer. In the square-planar description, the Cu(II) atom is displaced out of the square plane [r.m.s. deviation = 0.048 Å] by 0.084 (1) Šin the direction of the apical occupant. In the crystal, adjacent complex dimers are linked by an amine N-H⋯N hydrogen-bond pair, also giving a centrosymmetric cyclic association [graph set R(2) (2)(8)], generating a linear chain parallel to [110].

Dichlorido(1-{(E)-[phen-yl(pyridin-2-yl-κN)methyl-idene]amino-κN}pyrrolidin-2-one-κO)copper(II) monohydrate.

The Cu(II) atom in the title compound, [CuCl(2)(C(16)H(15)N(3)O)]·H(2)O, is N,N',O-chelated by the neutral Schiff base ligand and exists in a square-pyramidal geometry. It is displaced by 0.316 (1) Šout of the square plane (r.m.s. deviation = 0.015 Å) in the direction of the apical Cl atom. The apical Cl atoms of adjacent complex units are hydrogen-bond acceptors to two water mol-ecules, the inter-action generating a centrosymmetric dimer through a cyclic R(4) (2)(8) association.

{2-[(2-Carbamoylhydrazin-1-yl-idene)methyl-κ(2)N(1),O]-5-meth-oxy-phenolato-κO(1)}chloridocopper(II).

The asymmetric unit of the title compound, [Cu(C(9)H(10)N(3)O(3))Cl], contains two independent mol-ecules with similar structures. The Cu(II) cation is N,O,O'-chelated by the deprotonated Schiff base ligand and is further coordinated by a Cl(-) anion in a distorted ClNO(2) square-planar geometry. In the crystal, adjacent mol-ecules are linked by N-H⋯O and N-H⋯Cl hydrogen bonds, forming a two-dimensional network parallel to [100].

Di-µ-azido-κ(4)N(1):N(1')-bis-({1-[(E)-phen-yl(pyridin-2-yl-κN)methyl-idene]thio-semi-carbazidato-κ(2)N(1),S}copper(II)).

In the title compound, [Cu(2)(C(13)H(11)N(4)S)(2)(N(3))(2)], the Cu(II) cation is N,N',S-chelated by the deprotonated Schiff base ligand and is coordinated by the azide anion, while an N atom from an adjacent azide anion bridges the Cu(II) cation at the apical position with a longer Cu-N distance of 2.533 (3) Å, completing the distorted N(4)S square-pyramidal coordination geometry. A pair of azide anions bridge the two Cu(II) cations, forming a centrosymmetric binuclear mol-ecule. In the crystal, the binuclear mol-ecules are linked by an N-H⋯N hydrogen bond into a ribbon running along the a axis.

(Anilino{(Z)-2-[(E)-5-bromo-3-meth-oxy-2-oxidobenzyl-idene]hydrazin-1-yl-idene-κ(2)O(2),N(2)}methane-thiol-ato-κS)(4,4'-di-methyl-2,2'-bipyridine-κ(2)N,N')zinc N,N-dimethyl-formamide monosolvate.

The asymmetric unit of the title compound, [Zn(C(15)H(12)BrN(3)O(2)S)(C(12)H(12)N(2))]·C(3)H(7)NO, contains two independent mol-ecules with a similar structure. The doubly deprotonated Schiff base ligand O,N,S-chelates to the metal atom, and the three coordinating atoms along with one N atom of the substituted 2,2'-bipyridine ligand constitute the square plane of the distorted square pyramid surrounding the metal atom. The apical site is occupied by the second N atom of the substituted 2,2'-bipyridine. The secondary amine group of the Schiff base dianion forms a hydrogen bond to the O atom of the dimethyl-formamide solvent. In the crystal, the phenyl ring of one of the two Schiff base anions is disordered over two positions in a 1:1 ratio. The crystal studied is a racemic twin.

Bis(1-phenyl-3-{(Z)-[phen-yl(pyridin-2-yl)methyl-idene]amino-κ²N,N'}urea-κO)nickel(II) dinitrate.

The Ni(II) atom in the title salt, [Ni(C19H16N4O)2](NO3)2, is N,N',O-chelated by two neutral Schiff base ligands in a distorted octa-hedral geometry. One nitrate ion inter-acts with the metal atom indirectly, in an outer-sphere type of coordination, through N-H⋯O hydrogen bonds; the other nitrate ion does not engage in any inter-actions and is equally disordered over two positions in the crystal.

(Z)-N,N-Dimethyl-2-[phen-yl(pyridin-2-yl)methyl-idene]hydrazinecarbothio-amide.

The title compound, C(15)H(16)N(4)S, exists in the Z conformation with the thionyl S atom lying cis to the azomethine N atom. The shortening of the N-N distance [1.3697 (17) Å] is due to extensive delocalization with the pyridine ring. The hydrazine-carbothio-amide unit is almost planar, with a maximum deviation of 0.013 (2) Šfor the amide N atom. The stability of this conformation is favoured by the formation of an intra-molecular N-H⋯N hydrogen bond. The packing of the mol-ecules involves no classical inter-molecular hydrogen-bonding inter-actions; however, a C-H⋯π inter-action occurs.

Synthesis and spectral investigations of Mn(II) complexes of pentadentate bis(thiosemicarbazones).

Five Mn(II) complexes of bis(thiosemicarbazones) which are represented as [Mn(H(2)Ac4Ph)Cl(2)] (1), [Mn(Ac4Ph)H(2)O] (2), [Mn(H(2)Ac4Cy)Cl(2)].H(2)O (3), [Mn(H(2)Ac4Et)Cl(2)].3H(2)O (4) and [Mn(H(2)Ac4Et)(OAc)(2)].3H(2)O (5) have been synthesized and characterized by elemental analyses, electronic, infrared and EPR spectral techniques. In all the complexes except [Mn(Ac4Ph)H(2)O], the ligands act as pentadentate neutral molecules and coordinate to Mn(II) ion through two thione sulfur atoms, two azomethine nitrogens and the pyridine nitrogen, suggesting a heptacoordination. While in compound [Mn(Ac4Ph)H(2)O], the dianionic ligand is coordinated to the metal suggesting six coordination in this case. Magnetic studies indicate the high spin state of Mn(II). Conductivity measurements reveal their non-electrolyte nature. EPR studies indicate five g values for [Mn(Ac4Ph)H(2)O] showing zero field splitting.

Synthesis, spectral characterization and crystal structure of N-2-hydroxy-4-methoxybenzaldehyde-N'-4-nitrobenzoyl hydrazone and its square planar Cu(II) complex.

A new aroyl hydrazone, N-2-hydroxy-4-methoxybenzaldehyde-N'-4-nitrobenzoyl hydrazone (H2L) and its mixed ligand Cu(II) complex [CuLpy] [py, pyridine] have been prepared. The ligand is characterized by elemental analysis, electronic, infrared and NMR spectral studies and the complex by electronic, infrared, EPR spectral studies and the magnetic susceptibility data. The structures of the compounds were determined by single crystal X-ray diffraction studies. Both the ligand and the Cu complex crystallize into a triclinic lattice with a space group of PI. From the crystal studies, it is concluded that the ligand molecule exits in the keto form in the solid state, while at the time of complexation, it tautomerises into the enol form. The complex is formed by the double deprotonation of the ligand molecule--both the phenolic and the enolic protons.

Salicylaldehyde 4,4'-(hexane-1,6-diyl)thiosemicarbazone.

The title compound, C14H19N3OS, is in the thioketo form, with the thione S and hydrazine N atoms cis with respect to each other so that the S atom is involved in inter- and intramolecular hydrogen bonds simultaneously. Intermolecular C-H...S and C-H...O hydrogen bonds result in one-dimensional polymeric chains of molecules along the a axis. A weak C-H...pi ring interaction binds the polymeric chains together.

Structural and spectral perspectives of a novel thiosemicarbazone synthesized from di-2-pyridyl ketone and 4-phenyl-3-thiosemicarbazide.

A new thiosemicarbazone, HL is synthesized from di-2-pyridyl ketone and 4-phenyl-3-thiosemicarbazide and structurally and spectrochemically characterized. 1H NMR, 13C NMR, COSY, HMQC and IR spectra of the compound are studied and the proton magnetic resonance spectrum reveals some unprecedented observations. The thione form is predominant in the solid state, as supported by the crystal structure and IR data, while a thiol-thione equilibrium is proposed in the solution state by NMR studies. The compound crystallizes into a monoclinic lattice with space group C2/c and the ZE conformation is exhibited by the thiosemicarbazone. Intra- and intermolecular hydrogen-bonding interactions give rise to a two-dimensional packing in the crystal lattice.

[Di-2-pyridyl ketone N4,N4-(butane-1,4-diyl)thiosemicarbazonato-kappa3N,N',S]dioxovanadium(V).

The V(V) atom in the title complex, [V(C(16)H(16)N(5)S)O(2)], is five-coordinate in a highly distorted square-pyramidal geometry, with the pyridyl N, the azomethine N and the thiolate S atoms of the di-2-pyridyl ketone N(4),N(4)-(butane-1,4-diyl)thiosemicarbazone ligand and one oxo ligand occupying the basal coordination positions, while the second oxo ligand occupies the apical position. The molecules are interconnected by weak intermolecular interactions, mainly of the C-H...O type, involving the oxo atoms.

2-Hydroxy-3-(4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium-4-yl)benzoate monohydrate.

The title molecule, C(13)H(13)N(3)O(3).H(2)O, is in the form of a monohydrated zwitterion. The tetrahydropyridinium ring adopts an envelope conformation and is nearly coplanar with the plane of the imidazoline ring. The water solvate molecule plays an important role as a bridge between zwitterions, forming molecular chains running along the c direction, which are interconnected by N-H.O hydrogen bonds into molecular ribbons. The crystal packing is further stabilized by another N-H.O and one O-H.N hydrogen bond, which interconnect the molecular ribbons.

Di-2-pyridyl ketone N4,N4-(butane-1,4-diyl)thiosemicarbazone.

The title compound, C(16)H(17)N(5)S, is in the thione form and crystallizes with two independent molecules in the asymmetric unit. In both molecules, the pentamethyleneimine five-membered ring adopts an envelope conformation, and in one of the molecules this ring shows positional disorder. The thione S and hydrazine N atoms are in the Z configuration with respect to the C-N bond.

Bis[1-(pyridin-2-yl)ethanone-kappa N 4-phenylthiosemicarbazonato-kappa 2N4,S]manganese(II).

One half of the molecule of the title complex, [Mn(C(14)H(13)N(4)S)(2)], is related to the other half by a twofold axis passing through the Mn atom. This high-spin Mn atom is six-coordinated, in an octahedral geometry, by the azomethine N, the pyridyl N and the thiolate S atom of two planar 1-(pyridin-2-yl)ethanone N(4)-phenylthiosemicarbazone ligands. In the crystal, the molecules are interconnected by N-H.S and C-H.N interactions, forming a three-dimensional network.