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Two 1D coordination polymers were synthesized by reaction of two ligands, 2-amino-4-picoline (2A4Pic) and quinoline-6-carboxylic acid (Qu-6-COOH) with two metal (II) nitrate (M = Cd and Cu) in the presence of azide as a linker. The synthesized metal complexes [Cd(2A4Pic)2(N3)2]n; (1) and [Cu(Qu-6-COO)(N3)(H2O)]n; (2) were isolated in single crystals and their X-ray structures revealed a 1D polymeric structure. Due to symmetry considerations, the asymmetric formula is half a [Cd(2A4Pic)2(N3)2] unit for 1 and one [Cu(Qu-6-COO)(N3)(H2O)] unit for 2. In complex 1, the Cd(II) is hexa-coordinated with two 2A4Pic molecules and four μ(1,1) azide units. Hence, the CdN6 coordination environment has a slightly distorted octahedral geometry. In 2, the Cu(II) is hexa-coordinated with three different ligands (Qu-6-COO¯, H2O and μ(1,1) N3¯) where all are connectors between the crystallographically related Cu(II) sites. Additionally, complex 2 distorted CuN2O4 octahedral geometry. In both complexes, the polymer arrays are connected by N…H hydrogen bonds and π–π stacking interactions. Based on Hirshfeld analysis, the percentages of N…H contacts are 43.1 and 27.4% for 1 and 2, respectively, while %C...C are 5.6 and 9.3%, respectively. Analysis of Cu-N, Cu-O, and Cd-N bonds using DFT calculations showed predominantly closed-shell coordination interactions with little covalent characters. Additionally, the negatively charged ligand groups were found to compensate the positive charge of the central metal ion to a larger extent than the electrically neutral ligands.

Two new Co(II) and Cu(II) azido complexes with 4-picoline (4-Pic) and pyridine-2-carboxaldoxime (HAld) were synthesized by self-assembly of the organic ligand and the M(II) nitrate in the presence of azide as a co-ligand. Their structures were determined to be [Co(4-Pic)4(H2O)(N3)]NO3*H2O*4-Pic (1) and [Cu(HAld)(Ald)(N3)] (2) using X-ray single crystal diffraction. In complex 1, the coordination geometry is a slightly distorted octahedron with a water molecule and azide ion located trans to one another. On the other hand, complex 2 has a distorted square pyramid CuN5 coordination sphere with N-atoms of the organic ligand as a basal plane and azide ion as apical. All types of intermolecular contacts and their contributions in the molecular packing were analyzed using Hirshfeld analysis. The intermolecular contacts, H…H (53.9%), O…H (14.1%), N…H (11.0%) and H…C (18.8%) in 1, and H…H (27.4%), N…H (27.7%), O…H (14.7%) and H…C (13.6%) in 2 have the largest contributions. Of all the contacts, the O…H, N…H and C…C interactions in 2 and the O…H, N…H and H…C in 1 are apparently shorter than the van der Waals radii sum of the interacting atoms. Atoms in molecules (AIM) topological parameters explained the lower symmetry of the coordinated azide in 1 than 2.

In the present work, a novel heterocyclic hybrid of a spirooxindole system was synthesized via the attachment of ferrocene and triazole motifs into an azomethine ylide by [3 + 2] cycloaddition reaction protocol. The X-ray structure of the heterocyclic hybrid (1″R,2″S,3R)-2″-(1-(3-chloro-4-fluorophenyl)-5-methyl-1H-1,2,3-triazole-4-carbonyl)-5-methyl-1″-(ferrocin-2-yl)-1″,2″,5″,6″,7″,7a″-hexahydrospiro[indoline-3,3″-pyrrolizin]-2-one revealed very well the expected structure, by using different analytical tools (FTIR and NMR spectroscopy). It crystallized in the triclinic-crystal system and the P-1-space group. The unit cell parameters are a = 9.1442(2) Å, b = 12.0872(3) Å, c = 14.1223(4) Å, α = 102.1700(10)°, β = 97.4190(10)°, γ = 99.1600(10)°, and V = 1484.81(7) Å3. There are two molecules per unit cell and one formula unit per asymmetric unit. Hirshfeld analysis was used to study the molecular packing of the heterocyclic hybrid. H···H (50.8%), H···C (14.2%), Cl···H (8.9%), O···H (7.3%), and N···H (5.1%) are the most dominant intermolecular contacts in the crystal structure. O···H, N···H, H···C, F···H, F···C, and O···O are the only contacts that have the characteristic features of short and significant interactions. AIM study indicated predominant covalent characters for the Fe–C interactions. Also, the electron density (ρ(r)) at the bond critical point correlated inversely with the Fe–C distances.

The synthesis and crystal structures of three heteroleptic complexes of Zn(II) and Cd(II) with pyridine ligands (ethyl nicotinate (EtNic), N,N-diethylnicotinamide (DiEtNA), and 2-amino-5-picoline (2Ampic) are presented. The complex [Zn(EtNic)2Cl2] (1) showed a distorted tetrahedral coordination geometry with two EtNic ligand units and two chloride ions as monodentate ligands. Complexes [Zn(DiEtNA)(H2O)4(SO4)]·H2O (2) and [Cd(OAc)2(2Ampic)2] (3) had hexa-coordinated Zn(II) and Cd(II) centers. In the former, the Zn(II) was coordinated with three different monodentate ligands, which were DiEtNA, H2O, and SO42−. In 3, the Cd(II) ion was coordinated with two bidentate acetate ions and two monodentate 2Ampic ligand units. The supramolecular structures of the three complexes were elucidated using Hirshfeld analysis. In 1, the most important interactions that governed the molecular packing were O···H (15.5–15.6%), Cl···H (13.6–13.8%), Cl···C (6.3%), and C···H (10.3–10.6%) contacts. For complexes 2 and 3, the H···H, O···H, and C···H contacts dominated. Their percentages were 50.2%, 41.2%, and 7.1%, respectively, for 2 and 57.1%, 19.6%, and 15.2%, respectively, for 3. Only in complex 3, weak π-π stacking interactions between the stacked pyridines were found. The Zn(II) natural charges were calculated using the DFT method to be 0.8775, 1.0559, and 1.2193 for complexes 1–3, respectively. A predominant closed-shell character for the Zn–Cl, Zn–N, Zn–O, Cd–O, and Cd–N bonds was also concluded from an atoms in molecules (AIM) study.

The role of metalloenzymes in tumor progression had broadened their application in cancer therapy. Of these, MMPs and CAs are validated druggable targets that share some pivotal signaling pathways. The majority of MMPs or CAs inhibitors are designed as single-target agents. Despite their transient efficacy, these agents are often susceptible to resistance. This set the stage to introduce dual inhibitors of correlated MMPs and CAs. The next step is expected to target the common vital signaling nodes as well. In this regard, VEGFR-2 is central to various tumorigenesis events involving both families, especially MMP-2 and CA II. Herein, we report simultaneous inhibition of MMP-2, CA II, and VEGFR-2 via rationally designed hybrid 1,2,4-triazolo[4,3-a]pyrimidinone acyclo C-nucleosides. The promising derivatives were nanomolar inhibitors of VEGFR-2 (8; IC50 = 5.89 nM, 9; IC50 = 10.52 nM) and MMP-2 (8; IC50 = 17.44 nM, 9; IC50 = 30.93 nM) and submicromolar inhibitors of CA II (8; IC50 = 0.21 µM, 9; IC50 = 0.36 µM). Docking studies predicted their binding modes into the enzyme active sites and the structural determinants of activity regarding substitution and regioselectivity. MTT assay demonstrated that both compounds were 12 folds safer than doxorubicin with superior anticancer activities against three human cancers recording single-digit nanomolar IC50, thus echoing their enzymatic activities. Up to our knowledge, this study introduces the first in class triazolopyrimidinone acyclo C-nucleosides VEGFR-2/MMP-2/CA II inhibitors that deserve further investigation.