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Two new coordination complexes of Cu(II) viz.; [Cu(bpy)2(NO3)]NO3·5H2O (1) and [Cu(phen)(Hdmpz)Cl2]·H2O (2) (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, Hdmpz = 3,5-dimethyl pyrazole) have been synthesized and characterized by single crystal X-ray diffraction, electronic spectroscopy, EPR, FT-IR spectroscopy and TGA. The nitrate anion and the water molecules in the lattice of 1 are involved in the formation of unconventional infinite supramolecular crown-like nitrate–water clusters. The unconventional enclathration of guest cationic complex moieties of 1 within the supramolecular nitrate–water crown hosts provides stability to the crystal structure. Crystal structure analysis of 2 reveals the presence of cooperative ternary π-stacked assemblies with enclathration of single guest water molecules in hexameric Cu(II) supramolecular host cavities. Theoretical calculations have been performed to analyse the non-covalent interactions in the compounds; focusing on the unusual H-bonding network/anion–π cooperative assemblies in 1 and two different π-stacked cooperative assemblies in 2. DFT studies reveal that the distribution and orientation of the H-bonds in the cooperative H-bonding network in 1 is the most favoured. The high interaction energies of (π–π)1 and (π–π)2 in π-stacked ternary assemblies of 2 can be attributed to the participation of the entire aromatic surfaces with antiparallel orientations and the cooperative C–H⋯Cl interactions respectively. The in vitro antiproliferative activities of the compounds considering cell cytotoxicity, apoptosis and DNA fragmentation assays reveal significant concentration dependent cytotoxicity in DL cancer cells with nominal effects in normal PBMC cells. The molecular docking and pharmacophore studies established the structure activity relationship of the compounds.

Two new coordination polymers of Zn(II), viz. {[Zn(Hdmpz)2(μ-male)]·(MeOH)(H2O)}n (1) and [Zn(3-AMpy)2(μ-fum)(H2O)2]n (2) (where Hdmpz = 3,5-dimethylpyrazole, male = maleate, fum = fumarate, and 3-AMpy = 3-aminopyridine), have been synthesized and characterized using elemental analysis, TGA, spectroscopic and single crystal X-ray diffraction techniques. The 1D polymeric chains of the polymers self-assemble into 2D supramolecular architectures via several non-covalent interactions. Differences in the structural topologies have been observed with the change of solvent from the methanol–water mixture in compound 1 to de-ionized water in compound 2. Unconventional enclathration of the solvent molecules, viz. MeOH, and the water in the crystal structure of 1 results in an interesting layered assembly. The influences of the metal coordination on the strength of the π-stacking interactions have been explored theoretically for compound 2, which confirms that the coordination of 3-AMpy to the Zn(II) centre strongly polarizes the π-cloud and increases the local dipole of 3-AMpy, thereby enhancing the strength of π-stacking interactions. The in vitro anticancer activities of the compounds have been explored in Dalton's lymphoma cancer cell lines considering cell cytotoxicity and apoptosis, and the results were compared with those observed for cisplatin (reference drug) under the same experimental conditions. The in silico molecular docking studies and the pharmacophore features further corroborate the cytotoxicity and apoptosis inducing ability of the compounds.

Two new coordination complexes of Cu(II) and Mn(II), viz., [Cu(bpy)(H2O)4]SO4·2H2O (1) and [Mn(4-CNpy)2(H2O)3SO4]·H2O (2) (bpy = 2,2′-bipyridine, 4-CNpy = 4-cyanopyridine), have been synthesized and characterized by using single crystal X-ray diffraction, elemental analysis, FT-IR spectroscopy, electronic spectroscopic techniques and TGA. The crystal structure of 1 uncovers the formation of sulfate–water assemblies involving lattice and coordinated water molecules, while complex 2 reveals the presence of unconventional weak T-shaped CN⋯CN contacts in the layered architecture. We have analysed the unconventional interesting interactions using DFT calculations, molecular electrostatic potential (MEP), the NCI plot and QTAIM computational tools. The interaction energies of the two H-bonded dimers in 1 are very large because of the coulombic attraction between the dicationic H-bonded donor and the dianionic acceptor. It is interesting to observe that despite the energy of the H-bonds being very small compared to the total dimerization energy, the final geometry of the assembly in 1 is due to the charge assisted directional H-bonds instead of the non-directional ion-pair interactions. The DFT study reveals that the T-shaped CN⋯CN interaction in 2 is very weak, in good agreement with the small MEP energy at the nitrile carbon atom. Anticancer studies of the compounds have been carried out using Dalton's lymphoma cell line using MTT and apoptosis assay. The results of compound 1 and 2 mediated cell cytotoxicity on the DL cancer cell line showed a significant concentration-dependent reduction in cell viability, while negligible cytotoxicity was observed in normal (PBMC) cells. The docking simulation results also confirm the interaction of the complexes with the active sites of amino acids of the target proteins. Furthermore, pharmacophore models (2D and 3D) for the compounds were mapped to the H-bond donor, positive ionisable area and hydrophobic features that are important for establishing biological activities. No hematotoxicity was recorded for the compounds after treatment in normal mice.

A new oxalato bridged polymeric Mn(III) coordination compound, {[Mn2(η2-C2O4)(H2O)2Cl4] 2(4-CNpy)}n (1) (C2O4 = oxalate, 4-CNpy = 4-cyanopyridine), has been synthesized and characterized using elemental analysis, and spectroscopic (IR, electronic, XPS) and single crystal X-ray diffraction techniques. Electronic and XPS analyses of the compound justify the presence of a Mn(III) center that is charge compensated by the two chlorido ligands and the oxygen atom of the bridged oxalate. 4-CNpy molecules in the lattice form unconventional H-bonded supramolecular dimers in the solid state assisted by antiparallel CN⋯CN dipole⋯dipole interactions, which has been confirmed using QTAIM and NCI plot analysis and supported by MEP surface analysis. Remarkably, this dimer concurrently establishes a weak anion–π interaction with the coordinated chlorido ligand. Unexpectedly, QTAIM analysis reveals the existence of an interesting O⋯π-hole(nitrile) contact involving the coordinated water molecule and the nitrile moiety that also contributes to the stabilization of the dimer in the crystal structure. To the best of our knowledge, the existence of such π-hole interaction involving nitrile derivatives has not been reported before. Compound 1 has been further screened for anticancer activity in the malignant Dalton's lymphoma (DL) cell line and the results were confirmed by molecular docking and pharmacophore features. Our findings indicated that the cytotoxicity of compound 1 is initially increased in a dose dependent manner (0.01–1 μM) and then decreased (5–10 μM), which is also affected by the reactive oxygen species (ROS) in the cells. Interestingly, very low cytotoxicity (5–14%) was observed in the case of healthy cells (PBMC) for similar experimental conditions.

Two new coordination compounds, viz., [Co(phen)(bz)(H2O)3]·bz (1) and [Zn(phen)2(H2O)Cl]·Cl·bzH·2H2O (2) (phen = 1,10-phenanthroline, bz = benzoate, bzH = benzoic acid) were synthesized from purely aqueous media, and characterized using elemental analysis, spectroscopic (IR, UV-Vis-NIR) and single crystal X-ray diffraction techniques. In the crystal structures of 1 and 2, supramolecular networks have been built involving the association of O–H⋯O, C–H⋯O, and π–π stacking interactions. The enclathration of the guest bzH molecule in the host monomers of Zn(II) brings rigidity to the structure of compound 2. Theoretical investigations have been carried out to rationalize interesting supramolecular assemblies that include cooperative anion–π/π–π/π–anion in 1 and DNA-relevant HB-array⋯π/π–π/π–HB-array interactions in 2, which have been characterized using NCI plots and Bader's theory of “atoms-in-molecules”. The complexes significantly inhibit cell viability by inducing apoptotic cell death in a Dalton's lymphoma (DL) cell line with negligible cytotoxicity in normal cells. A molecular docking study and pharmacophore features reveal that compounds 1 and 2 interact and are accommodated well in the active site of anti-apoptotic proteins. Antimicrobial studies against a few pathogenic organisms suggest that the compounds are active against Gram-positive and Gram-negative bacteria and have relatively better antibacterial activity in comparison to phen.

Two new Ni(II) coordination complexes of pyrazole and acetato ligands, involving nitrate and chloride counter anions, viz. [Ni(Hdmpz)2(CH3COO)(H2O)3]NO3·2H2O (1) and [Ni(Hdmpz)2(CH3COO)(H2O)3]Cl (2) (where Hdmpz = 3,5-dimethylpyrazole), have been synthesized in purely aqueous medium at room temperature. The complexes have been characterized by elemental analysis, FT-IR, electronic spectroscopy, PXRD, TGA and single crystal X-ray diffraction. The H-bonds established between the isostructural cationic [Ni(Hdmpz)2(CH3COO)(H2O)3]+ moieties of both complexes can be classified as anti-electrostatic H-bonds (AEHBs) and these have been studied using DFT calculations. Remarkably, in one case these AEHBs exhibit favorable interaction energies, thus indicating that the attractive nature of the H-bonds is able to compensate the pure electrostatic repulsion. The analyses of the cell viability results for the DL cell line show a significant concentration dependent decrease by compounds 1 and 2 with a negligible cytotoxic effect observed against normal cells (PBMC) in comparison to the cancer cells (DL). The cytotoxic activity of these compounds in DL cells occurs via apoptosis. Molecular docking and SAR analysis reveal that the compounds possess high binding affinities against most common cancer target proteins.

A new fumarato bridged Zn(II) coordination polymer viz. catena[μ-fumaratobis(3,5-dimethylpyrazole)zinc(II)trihydrate],{[Zn2(μ-fum)2(Hdmpz)4]·3H2O}n (1) (where, fum = fumarate, Hdmpz = 3,5-dimethylpyrazole) has been synthesized in purely aqueous medium at room temperature. The compound is structurally characterized by single crystal X-ray diffraction, FT-IR, electronic spectroscopy, PXRD and TGA. The zig-zag polymeric chain of 1 self assembles into a 2D supramolecular network via C H⋯π, C H⋯C, N H⋯O and C H⋯O interactions. Particularly relevant in 1, since in addition to the aforementioned non-covalent interactions, the electron rich π-system of fumarate is involved in energetically significant unconventional π–π contacts with the electron poor π-cloud of Hdmpz, which have been analyzed by DFT calculations and characterized using the non-covalent interaction (NCI) plot index. The strong H-bond agrees well with the MEP analysis since it is established between the H-bond donor involving NH group of Hdmpz and the H-bond acceptor involving O-atom of carboxylate moiety. The compound has been investigated for anticancer activities considering cell cytotoxicity, apoptosis and molecular docking as parameters in Dalton’s lymphoma (DL) malignant cancer cell line and results were compared with cisplatin (reference drug) under the same experimental conditions. Interestingly, negligible cytotoxic effect was observed against normal cells (PBMC) in comparison to the cancer cells (DL). The treatment of the compound caused appearance of apoptotic cells as evident by fluorescence based nuclear morphology study. The in silico study reveals that the compound interacts with the antiapoptotic proteins such as bcl-2, bcl-XL and Mcl-1 which may lead to apoptotic cell death.

Two new isostructural coordination compounds of Ni(II) and Mn(II) viz. [Ni(H2O)4(Hdmpz)2]ADS (1) and [Mn(H2O)4(Hdmpz)2]ADS (2) (where, Hdmpz = 3,5-dimethylpyrazole, ADS = anthraquinone-1,5-disulfonate) have been synthesized in aqueous medium at room temperature and characterized them using elemental analysis, TGA, FT-IR, electronic spectroscopy and single crystal X-ray diffraction techniques. Coordination compounds involving ADS anions in the crystal lattice are scarcely reported in the literature. Crystal structure analysis reveals the presence of unconventional O∙∙∙O dichalcogen bonding interaction between the O-atoms of neighbouring ADS moieties of the compounds. Aromatic π-stacking and unusual charge assisted O‒H∙∙∙O and C‒H∙∙∙O hydrogen bonds (CAHBs) are also involved in the stabilization of the crystal structures. Theoretical calculations have been performed to analyze the CAHBs, π-stacking and O∙∙∙O dichalcogen bonding interactions observed in the solid-state structures of 1 and 2 using DFT calculations, MEP surface analysis, QTAIM and NCI plot index computational tools. The relatively larger interaction energy observed for Ni(II) compound can be attributed to the higher contribution of the CAHBs than that for the Mn(II) complex. The energy associated to the O•••O dichalcogen bonding interaction is small (0.6 kcal/mol) and comparable with the weak C‒H•••O contact observed in compound 2. In vitro antiproliferative activities of the compounds considering cell cytotoxicity and apoptosis reveal the cytotoxic potential of the compounds in Dalton's Lymphoma (DL) cancer cells with negligible cytotoxicity in normal PBMC cells. Molecular docking simulation of the compounds with antiapoptotic proteins reveals significant affinity of the compounds with the active sites of the antiapoptotic proteins.

Two new Ni(II) coordination complexes involving fumarate and 1,10-phenathroline viz.; [Ni2(phen)2(µ-fum)(H2O)6](fum)·6H2O (1) and [Ni(phen)2(H2O)2](0.5 fum)(NO3)·4H2O (2) (fum = fumarate, phen = 1,10-phenanthroline) have been isolated in aqueous medium at room temperature. Crystal structure analyses of the compounds reveal the presence of cooperative (π–π)2/(π–π)1/(π–π)2 stacked ternary assemblies which provide stabilities to the layered architectures. The lattice water and the large counter anions in the lattice of the compounds are involved in the formation of unconventional discrete cyclic fumarate-water, fumarate-water-nitrate clusters and infinite nitrate-water 1D chains that are very scarcely reported in the literature. The energetically significant π-stacked dimers observed in the biologically relevant ternary assemblies of the crystal structures are further studied theoretically using DFT calculations and NCI plot index computational tools. DFT calculations reveal that the cooperative (π–π)2 binding mode of compound 1 is energetically more significant than (π–π)1 Moreover, the study also reveals that for the equivalent cooperative (π–π)1 stacking interactions in both the structures, the energy is unexpectedly higher for compound 2 than that observed for compound 1. Both the compounds induce significant cytotoxicity in Dalton's lymphoma (DL) cancer cells by inducing apoptotic cell death with negligible cytotoxicity in normal cells. Decrease in the mitochondrial membrane potential (MMP) of DL cells after treatment with the compounds also corroborates the apoptotic cell death. The molecular docking and pharmacophore features reveal that the compounds interact and accommodated well with the active sites of anti-apoptotic proteins.

Two Ni(II) and Cu(II) coordination compounds viz. [Ni(phen)3](0.5adp)(2NO3)·4.5H2O (1) and [Cu4(phen)4(H2O)2(OH)4]4NO3·2H2O (2) (where, phen = 1,10-phenanthroline and adp = adipic acid) have been isolated in aqueous medium and characterized by single crystal XRD, TGA, elemental analysis and spectroscopic techniques (FT-IR and electronic). Crystal structure analysis of compound 1 reveals the unconventional enclathration of adp moieties in the tetrameric supramolecular host cavities via O(adp)···π and C–H···π interactions. The formation of discrete [(NO3)4(H2O)10]4− cores in 1 and unusual enclathration of the nitrate water clusters in the supramolecular host cavity of 2 provide additional reinforcement to the layered assemblies. DFT calculations and NCI plot computational tools have been employed to investigate the energetically significant enclathrated adp moieties in supramolecular host cavities of 1 and the antiparallel π-stacked ternary assemblies involving regium-π(chelate) interaction in 2. To the best of our knowledge, this is the first report of enclathration of adipic acid, a long chain aliphatic dicarboxylic acid; and non-covalent regium-π bonding interaction involving chelate ring in metal organic compounds. Finally, the compounds have been screened for in vitro antiproliferative activities in Dalton's Lymphoma (DL) cancer cell lines considering cell cytotoxicity, apoptosis and molecular docking. The compounds exhibit considerable cytotoxicity in DL cells with nominal effects in healthy normal PBMC cells. The docking study reveals the effective binding affinity of the compounds with the active sites of BCL family antiapoptotic proteins.

Two Mn(II) and Ni(II) coordination complexes viz. [Mn(phen)2(2,6-PDC)]·2CH3OH (1) and [Ni(2,6-PDC)2][Ni(H2O)4(en)]·6H2O (2) (phen = 1,10-phenanthroline, 2,6-PDC = 2,6-pyridinedicarboxylate and en = ethylenediamine) have been isolated at ambient conditions and characterized by elemental analysis, FT-IR, electronic spectroscopy, TGA and single crystal X-ray diffraction. Switching the solvent from methanol to water has changed the structural topologies of the compounds. Compound 1 is composed of a hepta-coordinated Mn(II) centre with two bidentate phen and one tridentate 2,6-PDC; whereas compound 2 is composed of cationic [Ni(H2O)4(en)]2+ and anionic [Ni(2,6-PDC)2]2– moieties with hexa-coordinated Ni(II) centers. Crystal structure analysis of compound 1 unfolds the presence of unorthodox O H(methanol)⋯π interactions involving the uncoordinated methanol molecules. The unusual enclathration of dual H-bonded guest (H2O)4 cores in the hexameric Ni(II) hosts in compound 2 provides rigidity to the crystal structure. The antiparallel π-stacked dimers and anti-cooperative HB···anion-π···HB assemblies observed in the solid-state structures of 1 and 2 respectively have been studied theoretically using DFT calculations and NCI plot index computational tools. In vitro anticancer evaluation of the compounds considering cell cytotoxicity and apoptosis assay showed significant concentration dependent cytotoxicity in Dalton’s lymphoma (DL) cancer cells with nominal effects in normal PBMC cells. To elucidate the possible mode of action of the cytotoxic behavior of the compounds, in silico docking studies have been carried out which revealed the efficient interaction of the compounds with the active sites of antiapototic cancer target proteins. The inhibitions of the activities of antiapoptotic target proteins have been further investigated using western blot analysis.

Two new benzoato bridged Mn(II) and Cu(II) dinuclear coordination compounds viz. [Mn2(bipy)2(4-Clbz)2(H2O)4]2(4-Clbz) (1) and [Cu2(bz)4(2-MePy)2] (2) (bipy = 2,2-bipyridine, 4-Clbz = 4-chlorobenzoate, bz = benzoate, 2-MePy = 2-methylpyridine) have been synthesized and characterized using elemental analysis, TGA, spectroscopic (FTIR, electronic, EPR) and single crystal X-ray diffraction techniques. Crystal structure analysis of compound 1 reveals the enclathration of guest 4-Clbz moiety in the supramolecular host tetramer which provides rigidity to the crystal structure. Further analysis reveals the presence of cooperative (π–π)2/(π–π)1/(π–π)2 ternary assemblies involving alternate coordinated and uncoordinated 4-Clbz moieties. In compound 2, intermolecular C H∙∙∙O, C H∙∙∙π and C H∙∙∙C contacts are involved in the formation of dimeric paddle wheel supramolecular assemblies which stabilizes the layered architecture. The cooperative interplay of H-bonding and π-stacked ternary assemblies of 1 has been studied theoretically using DFT calculations, MEP surface and NCI Plot computational tools. The large interaction energies along with the NCI plot index analysis confirm that the π-stacking assemblies in combination with the H-bonds are strong binding motifs. In vitro anticancer activity of the compounds considering cytotoxicity and apoptosis assays reveal significant concentration dependent cytotoxicity in Dalton's lymphoma (DL) cancer cell lines with nominal effects in normal healthy PBMC cells. Molecular docking study reveals the efficient interaction of the compounds with the antiapoptotic BCL family target proteins.

Two pyridinedicarboxylato bridged 1D coordination polymers of copper(II) viz.; {[Cu(2,5-PDC)(Hdmpz)2]·H2O}n (1) and {[Cu(2,3-PDC)]·10H2O}n (2) (where, Hdmpz = 3,5-dimethyl pyrazole, PDC = pyridinedicarboxylate) have been isolated and characterized using TGA, elemental analysis, spectroscopic (IR, electronic) and single crystal X-ray diffraction techniques. Crystal structure analysis of the compounds 1 and 2 reveals that unconventional C–H⋯π(carbonyl) and intramolecular O⋯C π-hole interactions provide stability to the crystal structures, respectively. Such C–H⋯π(carbonyl) and intramolecular O⋯C π-hole interactions are scarcely reported in the literature. Theoretical calculations have been performed to analyze the unconventional non-covalent interactions observed in the solid-state structures of 1 and 2 using NCI plot and QTAIM computational tools. We have also theoretically explored the semi-coordination (regium) Cu-Oaxial bonds present in the compound 2. The polymers have been further investigated for potential antiproliferative activities considering cell viability and apoptosis assays against Dalton’s lymphoma (DL) cancer cell lines and the results were compared with cisplatin (reference drug) in the same experimental conditions. The compounds significantly induce cytotoxicity in DL cells with nominal cytotoxicity in normal PBMC cells. The molecular doking simulation performed with the antiapoprotic protiens reveals strong binding affinities of the compounds with the active sites of the target proteins. To establish structure activity relationship (SAR), pharmacophore studies have been carried out to investigate the key pharmacophore features of the structures of the compounds responsible for biological activities.

Two new coordination compounds of Ni(II) and Cu(II), viz. [Ni(phen)2Cl(H2O)] 4-NO2bz·3H2O (1) and [Cu(phen)2Cl]Cl·5H2O (2) (phen = 1,10-phenanthroline, 4-NO2bz = 4-nitrobenzoate) have been synthesized and characterized by single crystal X-ray diffraction, elemental analysis, FT-IR, electronic spectroscopy, TGA and EPR. The detailed crystal structure analysis of the Werner Type Clathrate 1 reveals the self-assembled unconventional enclathration of 4-NO2bz moieties in supramolecular Ni(II) hosts. In addition to the conventional discrete (H2O)n clusters in the crystal structure of 2, the layered architecture involves enclathration of single guest water molecules in the Cu(II) supramolecular hosts. We have theoretically analysed the biologically relevant anti-parallel π-stacking interactions in compound 1 and two types of anion–π interactions involving coordinated and uncoordinated chloride ions in compound 2. MEP surface analysis and DFT calculations reveal that the anti-parallel π-stacking interaction in 1 is energetically significant and enhanced upon complexation of the ligands to the Ni(II) centre. Remarkably, studies also reveal that in addition to the conventional anion⋯π interaction involving the chloride anion in the lattice, the unusual Cl(chlorido)⋯π interaction observed in the crystal assembly of 2 is also energetically significant. The antiproliferative potential of the compounds 1 and 2 have been studied in Dalton’s Lymphoma (DL) malignant cancer cell lines considering MTT cell viability and apoptosis assays. The compounds 1 and 2 exhibited significant concentration dependent increase in cell cytotoxicity and apoptosis in DL cells with negligible cytotoxicity in normal (PBMC) cells.

Two new coordination compounds viz. [Ni(2,6-PDC)(Hdmpz)(H2O)2]∙H2O (1) and [Zn(3-CNpy)2Cl2] (2) (2,6-PDC = 2,6-pyridinedicarboxylate, Hdmpz = 3,5-dimethylpyrazole, 3-CNpy = 3-cyanopyridine) have been synthesized and characterized using elemental analysis, thermogravimetric analysis, electronic, infrared spectroscopy and single crystal X-ray diffraction techniques. Crystal structure analyses reveal the presence of supramolecular assemblies involving interesting dimers with unconventional contacts in the compounds. DFT (Density Functional Theory) calculations on the supramolecular dimers in the crystal structure of 1 reveal that the sum of contributions of anion–π, π–π and other long range interactions due to the approximation of the bulk monomers is energetically significant. Molecular Electrostatic Potential (MEP) surface and Quantum Theory of Atoms in Molecules (QTAIM) analyses on the interesting supramolecular dimers of the crystal structures of 2 reveal the presence of unconventional anion⋯π contacts involving coordinated chlorido ligands and C–H⋯π(nitrile) interactions involving the π-system of the nitrile moiety of 3-cyanopyridine. Remarkably, Atoms in Molecules analysis also confirms the existence of energetically significant unconventional anti-parallel nitrile⋯nitrile interaction in the crystal structure of 2. Cell cytotoxicity of the compounds performed in Dalton's lymphoma (DL) malignant cancer cell line showed effective potency with negligible cytotoxicity in normal cells (~12%). It is interesting that compound 1has excellent cytotoxic potency with IC50 closer to cisplatin and can bind different biological targets with similar signalling pathways. Structure activity relationship (SAR) analyses of 1 and 2 based on pharmacophore modelling reveal that the molecular features associated with the structures of the compounds play important role in the biological activities.

Two new isostructural coordination compounds of cobalt(II) and zinc(II) involving 2,2′-bipyridine and 2,5-pyridine dicarboxylate, viz. [Co(2,5-PDC)(bipy)2]·7H2O (1) and [Zn(2,5-PDC)(bipy)2]·7H2O (2) (bipy = 2,2′-bipyridine and 2,5-PDC = 2,5-pyridine dicarboxylate), have been synthesized in purely aqueous medium at room temperature. The compounds have been further characterized by single crystal X-ray diffraction, FT-IR, electronic spectroscopy, thermal and elemental analysis. Several non-covalent interactions, such as C H⋯O and anti-parallel π-stacking contacts, build up the supramolecular layered architectures of the crystal structures. Further analysis of the crystal structures reveals the self-assembled enclathration of a 1D H-bonded (H2O)8 chain into the supramolecular hexameric host cavity which brings rigidity to the crystal structures. Such unconventional enclathration of H-bonded water molecules in a metal–organic supramolecular host involving bipy is scarcely described in the literature. We have theoretically evaluated the strength of the anti-parallel π-stacking interactions that are crucial for the stabilization of the supramolecular dimers of the compounds. The influences of the metal coordination on the strength of the π-stacking interactions have been confirmed using DFT calculations and NCI plot computational tools. The antiproliferative activities of the compounds have been investigated in the DL cell line using MTT cell viability and apoptosis assays. The compounds significantly induce concentration dependent cell cytotoxicity and apoptosis in DL cells with negligible cytotoxicity in normal (PBMC) cells. A molecular docking study also reveals a strong interaction of the compounds with the active site of anti-apoptotic BCL proteins. Pharmacophore features of the structures of the compounds responsible for the biological activities were also generated to establish a structure activity relationship (SAR).

Three new coordination compounds of types [Co(py)(2,6-PDC)(H2O)2].H2O (1), [Ni(py)(2,6-PDC)(H2O)2].H2O (2) and [Cu(py)(2,6-PDC)(H2O)].2H2O (3) (py = pyridine, 2,6-PDC = Pyridine-2,6-dicarboxylate) have been synthesized from purely aqueous media and characterized using elemental analysis, spectroscopic (IR and electronic) and single crystal X-ray diffraction techniques. Several supramolecular contacts of types O H⋯O, C H⋯O, C H⋯π, C H⋯C and π–π stacking stabilize the crystal structures. The layers in the crystal structures stack in perpendicular direction resulting in 1D channel with enclathrated water molecules. The strength of the antiparallel π-stacking interactions involving the pyridine rings in the supramolecular dimer of the compounds have been evaluated using DFT calculations and the influence of the pyridine coordination to the strength of the stacking assembly have been confirmed. The anti-proliferative potential of the compounds has been studied in Dalton’s lymphoma (DL) cell line by using MTT cell viability assay and apoptosis assay. All the three complexes exhibit short term (24 h) cytotoxicity (∼20–30%) through apoptotic cell death with negligible cytotoxicity (∼5–10%) in normal cells. In silico docking simulation has been performed with apoptosis regulator protein BCL-2 for the identification of possible molecular mode of action of the synthesized complexes. The pharmacophore features based on structure activity relationship (SAR) of the complexes have been identified. The SAR results reveal that the molecular features such as, hydrophobic, aromatic, positive ionizable, negative ionizable, H-bond donor and acceptor and halogen bond donor associated with the structures of the compounds play important role in the biological activities. The ADMET features, viz., physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness of the synthesized complexes have been investigated.

A new coordination polymer of nickel(II) involving bridging fumarato viz. catena[μ-fumarato(1,10-phenanthroline monohydrate(diaqua))nickel(II)trihydrate], {[Ni(μ-fum)(phen)(H2O)2].3H2O}n (1) (where, fum = fumarate, phen = 1,10-phenanthroline monohydrate) has been synthesized in purely aqueous medium at room temperature. The crystal structure of the polymer has been determined by single crystal X-ray Diffraction analysis. The polymer has been characterised by FT-IR, electronic spectroscopy, thermal and elemental analysis. The zig-zag polymeric chain of 1 self assembles into 2D supramolecular network architecture via reciprocal π-π stacking interactions. The lattice water molecules are involved in the formation of unique supramolecular octameric linear water clusters involving alternate trimeric rings that stabilizes the 2D network architecture. The crystal structure of the polymer also reveals the self-assembled enclathration of (H2O)8 cluster into polymeric Ni(II) host involving fum ligands that brings rigidity to the structure. Theoretical calculations have been performed to analyse the non-covalent interactions observed in the solid-state structure of 1. In particular, we have analysed the π–π stacking interactions between the phen ligands and also the energetically significant unconventional O H⋯π interaction involving the π-system of fum. For the latter, we have investigated the ability of the double bond of fum (coordinated to Ni) to establish O H⋯π interaction with water in comparison to fum acid and simple ethene. Finally, the polymer has been investigated for potential anticancer activities considering cell cytotoxicity, apoptosis and molecular docking as a major parameters against Dalton’s lymphoma (DL) malignant cancer cell line and the results were compared with cisplatin (reference drug) under the same experimental conditions. DNA interaction and fragmentations have been investigated for compound 1 and pharmacophore features establish structure activity relationship (SAR).

Three new isostructural coordination solids viz. [Co(3-CNpy)2(2-ClBz)2(H2O)2] (1), [Mn(3-CNpy)2(2-ClBz)2(H2O)2] (2) and [Zn(3-CNpy)2(2-ClBz)2(H2O)2] (3) (3-CNpy = 3-cyanopyridine, 2-ClBz = 2-chlorobenzoate) have been synthesized from purely aqueous media and characterized by X-ray crystal structure analysis, FT-IR, electronic spectra and TGA. Several non-covalent hydrogen bonding interactions of the types O H⋯O, C H⋯O, C H⋯N, C H⋯Cl and π-π stacking contacts build up the supramolecular networks in the crystal structures. Electrostatically enhanced π-π interactions are observed in 1–3 between the phenyl rings of 2-ClBz and pyridine ring of 3-CNpy of the monomeric units of the complexes. We have used the molecular DFT calculations to evaluate energetically the strength of these contacts and also to analyze the effect of the metal on the interaction energies. The energetic features of the H-bonding and π-stacking interactions for 1–3 reveal that the H-bonded assembly is more favorable than the π-stacked contacts. The electrostatically enhanced energy of the π-stacking interactions is stronger than that usually observed for π-stacking interactions involving arenes. The cytostatic potential of all complexes have been studied in Dalton’s lymphoma (DL) cell line by MTT assay, apoptosis assay and further corroborated with molecular docking simulation. The complexes exhibit cytotoxicity (∼25–30%) through apoptotic cell death with negligible cytotoxicity (∼5–10%) in normal PBMC cells. In silico-docking techniques have been performed with apoptosis regulator protein BCL-2 for the identification of critical amino acids and their possible binding affinity with the synthesized complexes. The pharmacophore features based on structure activity relationship (SAR) of the complexes have been identified and the study reveal that the features viz., hydrophobic, aromatic, positive ionizable, negative ionizable, H-bond donor and acceptor and halogen bond donor properties play important role for the biological activities of the complexes.

Two new coordination complexes viz. [Mn2(μ‑O,O′‑4‑Mebz)2(bpy)2(μ2‑H2O)(4‑Mebz)2] (1) and [Zn(bpy)(pdc)(H2O)]·3.5H2O (2) (where bpy = 2,2′‑bipyridine, 4‑Mebz = 4‑methyl benzoate and pdc = 2,6‑pyridine dicarboxylate) were synthesized and structurally characterized by single crystal X-ray diffraction, FT-IR, electronic spectroscopy, Thermogravimetric Analysis (TGA) and Powder X-ray diffraction (PXRD) techniques. Complex 1 consists of a dinuclear Mn(II) unit bridged by a solvent water molecule while 2 is a mononuclear complex. The supramolecular assemblies found in the solid state of both complexes have been described. In 2, several π-stacking interactions modes have been further studied using Density Functional Theory (DFT) calculations. Furthermore, the activity of the complexes against a few pathogenic bacteria has been studied and confirmed. Finally, the antiproliferative activities of both complexes have been studied in T-cell lymphoma cell line by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis assay and molecular docking simulation. Both the complexes exhibit gratifying cytotoxicity through apoptotic cell death with negligible cytotoxicity (~5–10%) in normal cells. It is worth mentioning that Mn(II) and Zn(II) complexes exhibit interaction modes with highly expressed cancer target proteins under study with higher binding affinity and the results are comparable with reference inhibitors.