Three multicomponent crystals of metformin were investigated to elucidate factors governing crystal architecture. Structures were determined by X-ray diffraction and analyzed using the Atoms-in-Molecules (AIM) approach, focusing on critical points and electron density topology. Three types of crystals were obtained: salt, cocrystal salt solvate and mixed salt with both organic and inorganic anions. Protonation of nitrogen atoms in metformin alters bond lengths and electron density, while strong intramolecular hydrogen bonds in hydrogenmaleate anions stabilize the structures and define the preferred anion geometry. Comparison with monoprotonated metformin revealed similar topological features despite differing protonation states. Mechanochemical synthesis via liquid-assisted grinding (LAG) enabled selective formation of specific crystalline forms, with the solvent type and acid polymorph influencing product distribution. These results highlight the critical roles of protonation, hydrogen bonding, and synthetic methodology in designing and controlling multicomponent metformin crystal structures.

The title compound, bis[mu-3-ethyl-5-(pyridin-2-yl)-1H-1,2,4-triazol-1-ido]bis[acetato(dimethylformamide)copper(II)], [Cu-2(C9H9N4)(2)(C2H3O2)(2)(C3H7NO)(2)] or [Cu-2(L (Et))(2)(OAc)(2)(dmf)(2)], is a triazolate complex, which contains two 3-(2-pyridyl)-5-ethyl-triazolates (L (Et))(-) in bidentate-bridged coordination modes. Both copper atoms are involved in the formation of a planar six-membered metallocycle Cu-[N-N](2)-Cu. The inversion center of the complex is located at the mid-point of the Cu & ctdot;Cu vector. Each Cu-II atom has a distorted trigonal-bipyramidal environment formed by the three nitrogen atoms of the deprotonated bridging 3-(2-pyridyl)-5-ethyl-triazolate unit, oxygen atoms of the OAc- group and dmf molecule. In the crystal, C-H & ctdot;O hydrogen bonds link the molecules into chains running along the c-axis direction.

A series of Cu(II) complexes was synthesized from the reaction of various copper(II) salts with 2-(3-pyridyl)-1,3-benzothiazole N-oxide (3PBTO), resulting in the following complexes: [Cu(3PBTO)4(BF4)2] (1), [Cu (3PBTO)4(CF3SO3)2] (2), [Cu(3PBTO)4(ClO4)2] (3), [(3PBTO)Cu-mu-(CH3COO)2)2-Cu(3PBTO)] (4), and [Cu (3PBTO)3(CH3CN)](NO3)2 (5). All complexes were characterized using elemental analysis and IR spectroscopy. Single-crystal X-ray diffraction analysis revealed that complexes 1-3 exist as mononuclear CuL4(anion)2 species in the solid state, with the central Cu ion in a six-coordinate environment. In these complexes, the four Cu-O bonds with the ligand molecules are relatively short, forming the square base of a tetragonal bipyramid, with ions molecules occupying the axial positions at relatively long distances from the central ion. These observations are further supported by the EPR spectrum of complex 5, which suggests a distorted square-planar coordination. Calculations performed for complex 3 using density functional theory (DFT) at the B3LYP/6-31G(d) level and reoptimized using the aug-cc-pVDZ basis set confirmed its experimentally observed geometry. Electronic analyses revealed a HOMO-LUMO energy gap of 3.7 eV, indicating high kinetic stability and low polarizability of this molecule. The structure of complex 4, Cu2L2(acetate)4, differs, with each Cu atom in a six-coordinate environment, bonded to four oxygen atoms from acetate anions, one N-O oxygen atom from the ligand, and the other Cu cation. The 2-(3-pyridyl)-1,3-benzothiazole N-oxide ligand acts as a monodentate ligand in all the complexes. FT-IR spectroscopy indicates that in complex 5, the acetonitrile molecule is coordinated to the central metal ion, and the nitrate anion exists in its ionic form.

Two new Schiff base complexes, [Cu₆(L)₆] (1) and [Co (HL)₂]OAc (2), were synthesized by condensation of the ligand (E)-5-bromo-2-[2-(hydroxymethyl)phenyliminomethyl] phenol (H₂L) with metal elements)copper/cobalt) in methanol. The H₂L ligand formed a bidentate hexanuclear structure with Cu(II) ion and a mononuclear complex with Co(III). The compounds were identified by conventional spectroscopic methods (elemental analysis, UV–Vis, and FT-IR), and their structures were determined by X-ray diffraction. The results showed that complex)1(has a Cu₆O₈ symmetric scaffold with Ci symmetry and complex)2(has C₂ symmetry with an octahedral coordination environment for the Co ion. Analysis of intermolecular interactions using Hirshfeld surface revealed the presence of prominent H…H, H…Br/Br…H and C…Br/Br…C interactions in complex)1(and H…O/O…H in complex)2(. Also, enrichment ratio showed that H…Br/Br…H, H…O/O…H, and C…C interactions are more favorable in both complexes. DFT calculations using the B3LYP/6-311G method and FMO analysis were performed to investigate the electronic structure and the agreement between theoretical and experimental UV–Vis data. Molecular dynamics (MD) simulations were performed to investigate the interactions between inhibitor molecules and bronze metal surfaces in corrosive environments. The results showed that complexes (1) and (2) are strongly adsorbed on the bronze (1 0 0) surface, which is facilitated by non-covalent interactions. These interactions help to form a stable protective layer and are essential for corrosion inhibition. The results of these simulations can be useful in understanding and developing effective strategies for corrosion inhibition. In conclusion, the molecular docking results against 6Y2F (coronavirus) and 1BG1 (colon cancer) proteins show appropriate affinity and stable energies, indicating the possibility of using these complexes as potential inhibitor candidates for coronavirus and colon cancer. In addition, the copper complex showed a more favorable total system energy and higher affinity for receptor interaction compared to the cobalt complex and the reference drug favipiravir. The molecular docking results of the studied complexes, compared to niclosamide (as the reference drug), indicated better performance of both complexes and their complete localization in the active site of the receptor.

Phosphonate analogues of alpha-amino acids are increasingly valued for their significant potential in medicinal chemistry. Fluorine is a "magic" element that plays a huge role in modulating the properties of organic compounds. In this work, we combined the two pharmacophores in the synthesis of three series of new alpha-aminophosphonates. These compounds were obtained by diastereoselective hydrophosphonylation of imines prepared by an environmentally friendly mechanochemical approach. Results of computational SwissADME analysis suggested favorable drug-like properties of the alpha-aminophosphonates and indicated their potential for interaction with diverse biological targets including proteases, showing promising pharmacokinetic profiles compared to 5-fluoro-2 '-deoxyuridine (FdU) used as a standard anticancer drug. Screening against ten cancer cell lines from seven types of cancer showed that five of the twenty compounds tested (1c, 2a, 2h, 3e, and 3f) exhibited superior activity against the HeLa cell line and lower cytotoxicity against normal MRC-5 cells than FdU. Compound 3e showed notable inhibitory effect on the MDA-MB-231 cell line, while 3a, 3h, and 3g demonstrated significant cytotoxic activity against U-87 MG and U-251 MG lines. Molecular docking highlighted the strong binding of compound 2a to the urokinase-type plasminogen activator (uPA) protein, with a binding affinity of -6.41 kcal/mol, suggesting the anti-metastatic potential of the compound. These findings enable to position the newly synthesized alpha-aminophosphonates as promising scaffolds for developing targeted anticancer therapies for metastatic cancers characterized by elevated uPA expression.

The antiproliferative and antibacterial activities of thiosemicarbazones increase markedly with the presence of metal ions. One of the factors determining the activity of metal thiosemicarbazone complexes is the coordination structure. In this study, the biological effects of new antimony (III) and bismuth (III) thiosemicarbazone complexes with different binding modes and geometrical structures were demonstrated. Three new complexes, with the formulae {[SbCl3(µ2-S-Hacptsc)(η1-S-Hacptsc)], 2/3H2O,1/3CH2Cl2}, {[SbCl3(κ2-S,N-Hacpmtsc)(η1-S-Hacpmtsc)2CH2Cl2]}, and{[BiCl3(η1-S-Hbzmtsc)3]·C2H5OH}, where Hacptsc: acetophenone thiosemicarbazone, Hacpmtsc: acetophenone-N-methyl thiosemicarbazone, Hbzmtsc: benzaldehyde-N-methyl thiosemicarbazone) were elucidated by different methods and deeply analyzed in accordance with their structure by X-ray structure analysis and Atoms-In-Molecules topological analysis. This analysis provided a deeper understanding of the coordination spheres of the Sb/Bi complexes. For instance, the first reported two binding modes of the same ligand are observed in a single crystal structure of antimony (III) halide complexes. Additionally, in one of the complexes, a solid-to-solid phase transition was detected and analyzed in detail. Those complexes, very unique in terms of their geometry, have also been tested for their in vitro cytotoxic activity against human adenocarcinoma cervical cancer (HeLa) cells, whereas antimony (III) complex 1is the most active complex of this study. Further, the antibacterial activity of the complexes has been screened against two Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and two Gram-positive (Staphylococcus epidermidis and Staphylococcus aureus) pathogenic bacteria. From the results, it is found that all the complexes exhibited significant activity against the Gram-negative pathogenic bacteria.

New bismuth (III) complexes with acetophenone-4-methyl-3-thiosemicarbazone (L) and halogens (Cl and Br) in both bridging and terminal positions have been synthesized and structurally characterized using single-crystal X-ray diffraction. The pure complexes (Cl or Br) were found to be highly isostructural, which motivated our attempts to create solid solutions of these complexes. A series of such compounds was prepared using various procedures and stoichiometries. A method for determining the mutual concentrations of different halogens, based on the positions of selected peaks in powder diffraction patterns, was tested and compared with other methods.

The advancement of ultra-sensitive optical manometers is crucial for exploring the behavior of materials under extreme conditions. Herein, we introduce a novel rare-earth complex Eu(bpyO(2))(4)(PF6)(3) as a promising candidate for high-precision pressure sensing, addressing the gap in sensitivity of existing luminescence manometers below 1 GPa. Through comprehensive high-pressure spectroscopic and single-crystal X-ray diffraction studies, we have found a phase transition in Eu(bpyO(2))(4)(PF6)(3) at 1.25 GPa, where the ambient pressure phase alpha (space group Pbcn) transforms to the high-pressure phase beta (space group P2(1)/n). This process reduces the contribution of intramolecular anagostic bonds complementing the coordination sphere modifying the observed emission spectra, underpinning the role of crystal engineering in the development of dual-mode (ratiometric and lifetime-based) luminescence manometers. The ratiometric mode, measuring the intensity ratio between two emission bands of Eu3+ ions, demonstrates a remarkable relative sensitivity, exceeding 120.7% GPa(-1) at approximately 1.6 GPa. The lifetime-based mode utilizes pressure-influenced luminescence kinetics and shows a maximal relative sensitivity of 55.1% GPa(-1), classifying it as the most sensitive optical manometer operating in this mode. The unique bimodal readouts and unparalleled sensitivity of Eu(bpyO(2))(4)(PF6)(3) across both modes represent a significant advancement in pressure sensing technologies.

Two isostructural (in room temperature) complexes of Bi(III) with halogens and sulfur ligands have been investigated in terms of the solid-to-solid phase transitions indicated by temperature. Both chloride and bromide (X) complexes of the general formula (µ 2 -X)-(BiX 2 L 2 ) 2 exhibit some phase transitions between 100 and 333 K, which, apart from the numerous similarities, show significant differences, which have been noted and analyzed in detail in this paper by using different techniques, i.e., powder and single crystal diffraction or DSC. The obtained results have also been collated with those obtained for solid solutions of both complexes.

Deoxyfluorinating reagents such as DAST and PyFluor can be successfully employed as tools for selective modification of γ-amino-α-hydroxyphosphonates.

Generation of well-defined potential metallotherapeutics for cancer treatment, one of the most population-threatening diseases, is challenging and an active area of modern research in view of their unique properties and thus multiple possible pathways of action in cells. Specifically, Schiff base ligands were recognized as very promising building blocks for the construction of stable and active complexes of numerous geometries and topologies. Incorporation of Ag(I) ions allows for the formation of flat complexes with potential unoccupied coordination sites, thus giving rise to specific interactions between the metallotherapeutic and biomolecule of interest. Herein, we present the design, synthesis and characterization of new Schiff base ligand L and its Ag(I) bimetallic complex [Ag2L2]2+ with two planar moieties formed around the metal ions and connected through cyclohexane rings, confirmed by X-ray measurements. The compounds were described in context of their potential use as anticancer drugs through DNA and BSA binding pathways by several spectroscopic methods (CD, UV-Vis, fluorescence). We revealed that both, L and [Ag2L2]2+, interact with similar affinity with CT-DNA (Kb~106 M−1), while they differ in the type and strength of interactions with the model albumin–BSA. [Ag2L2]2+ binds BSA in both a dynamic and static manner with the Ksv = 8.8 × 104 M−1 in the Trp-134 and Trp-213 sites, whereas L interacts with BSA only dynamically (KSV = 2.4 × 104 M−1). This found further confirmation in the CD studies which revealed a reduction in α-helix content in the albumin of 16% in presence of [Ag2L2]2+.

The benzimidazole-based ligand containing polymerizable styrene group has been prepared via condensation of picolinaldehyde derivative containing styrene moiety and benzimidazole-based hydrazine. The ligand reacted with iron(II) tetrafluoroborate and iron(II) trifluoromethanesulfonate giving red-brown complexes of Fe(II) ions of formula [FeL2]X2, where X = CF3SO3− (1) or BF4− (2). Reductive electropolymerization was used to obtain a thin layer of the polymeric complex, poly-1. Further investigation of electrochemical properties of the compound by cyclic voltammetry showed two quasi-reversible redox processes assigned to electrooxidation and electroreduction of the polymer. Spectroelectrochemical measurements confirmed that the polymer undergoes the color changes during oxidation and reduction process. The polymer in its neutral state (Fe(II)) is yellow and it exhibits absorption band at 370 nm, after oxidation to Fe(III) state absorption band shifts to 350 nm and the polymer is almost colorless. While the metal ions are reduced to Fe(I) absorption band at around 410 nm has been observed and the polymer changed its color to intense yellow. The stability of the polymer during multiple oxidation/reduction cycles has also been investigated.

The aim of the reported research is to evaluate the significance and potential role of the thiophene moiety in potential DNA and BSA targeting drugs. For this purpose a Thiophene-BenzoThiazole tandem molecule (TBT) and its mononuclear silver(I) complex [Ag(TBT)(2)](+) was synthesized. The research was carried out using spectroscopic techniques such as circular dichroism (CD), UV-Vis and fluorescence. Based on the presented results the intercalating type of binding to DNA by complex [Ag(TBT)(2)](+) and ligand TBT was observed. The binding is spontaneous in both cases and the Kb values of both compounds are similar (K-b = 6. 40 x 10(5) and K-b = 5.83 x 10(5) for ligand TBT and complex [Ag(TBT)(2)](+), respectively). Yet, this type of interaction was confirmed in ethidium bromide competitive binding experiments and a special emphasis should be put on the higher Ksv value for complex [Ag(TBT)(2)](+) (5.1 x 10(4)) than ligand TBT (3.4 x 10(4)), since it may be the result of the bisintercalation of the complex. It has found confirmation in the increase of the melting temperature (T-m) of DNA treated with complex [Ag(TBT)(2)](+) of similar to 5 degrees C, while in analogues experiment with ligand TBT T-m was only similar to 1 degrees C higher. The bisintercalation of the complex is possible since two TBT ligands are bound to the metallic center with planar thiophene moieties placed on the same site. Furthermore, the complex [Ag(TBT)(2)](+) caused more significant changes in the secondary structures of the model protein BSA than the ligand TBT as determined by CD (reduction of alpha-helix content by 95 times in presence of the complex vs. stabilization of BSA structure with TBT). It needs to be emphasized, that both compounds bind to BSA via static quenching mechanism, however [Ag(TBT)(2)](+) has a higher affinity to it than the ligand itself (as evidenced by the extent of hyperchromism). Both compounds interact in hydrophobic site of the protein, however [Ag(TBT)(2)](+) exhibits higher Stem-Volmer constant K-sv 1.66 x 10(5) in comparison to TBT K-sv = 1.24 x 10(5). The Scatchard equation allowed one to estimate the compound:BSA binding ratio as 1:1 and 2:3 for ligand and complex, respectively. Moreover, the binding constant Kb is higher for complex (K-b = 4.05 x 10(7)) than ligand (K-b = 3.70 x 10(5)). It confirms that, indeed, both compounds may be distributed by albumins in the body, however the {(BSA)(3) - [Ag(TBT)(2)](2)(+)} adduct is more stable. The synchronous fluorescence spectra indicated that both compounds bind better in Trp than Tyr residues, therefore they may serve as potential molecular targets. (C) 2020 Elsevier B.V. All rights reserved.

The intermolecular interactions in the structures of a series of Schiff base ligands have been thoroughly studied. These ligands can be obtained in different forms, namely, as the free base 2-[(2E)-2-(1H-imidazol-4-ylmethylidene)-1-methylhydrazinyl]pyridine, C10H11N5, 1, the hydrates 2-[(2E)-2-(1H-imidazol-2-ylmethylidene)-1-methylhydrazinyl]-1H-benzimidazole monohydrate, C12H12N6·H2O, 2, and 2-{(2E)-1-methyl-2-[(1-methyl-1H-imidazol-2-yl)methylidene]hydrazinyl}-1H-benzimidazole 1.25-hydrate, C13H14N6·1.25H2O, 3, the monocationic hydrate 5-{(1E)-[2-(1H-1,3-benzodiazol-2-yl)-2-methylhydrazinylidene]methyl}-1H-imidazol-3-ium trifluoromethanesulfonate monohydrate, C12H13N6+·CF3O3S-·H2O, 5, and the dicationic 2-{(2E)-1-methyl-2-[(1H-imidazol-3-ium-2-yl)methylidene]hydrazinyl}pyridinium bis(trifluoromethanesulfonate), C10H13N52+·2CF3O3S-, 6. The connection between the forms and the preferred intermolecular interactions is described and further studied by means of the calculation of the interaction energies between the neutral and charged components of the crystal structures. These studies show that, in general, the most important contribution to the stabilization energy of the crystal is provided by π-π interactions, especially between charged ligands, while the details of the crystal architecture are influenced by directional interactions, especially relatively strong hydrogen bonds. In one of the structures, a very interesting example of the nontypical F...O interaction was found and its length, 2.859 (2) Å, is one of the shortest ever reported.

Herein, we present application of α-amino-β-fluorophosphonates for the construction of their dipeptide analogues. α-Amino-β-fluorophosphonates were prepared in a XtalFluor-E mediated deoxyfluorination of α-hydroxy-β-aminophosphonates. The reaction proceeds through an aziridinium ion formation, which was confirmed by the formation­ of a hexacoordinate phosphorus compound. Moreover, the absolute configuration of the obtained compounds was determined by X-ray analysis, which proved the stereochemistry.

Nucleophilic additionHydride reduction

The charge density distribution in N-n-butyltetrachlorophthalimide was experimentally determined using high-resolution X-ray diffraction data and the Hansen–Coppens multipole formalism.

Synthesis of two homoleptic and five heteroleptic zinc (II) carboxylate complexes with two different ligands: HL1 = 3-chlorobenzoic acid and HL2 = 2-(4-chlorophenyl) acetic acid have been reported in this paper. The general formulae of the two homoleptic complexes are: Zn(L1)2(1), and Zn(L2)2(2). Similarly, the general formulae for two different types of heteroleptic complexes are: (Type-I): [(Zn)2(L1)4(bipy)2(H2O)] (3), [Zn(L2)2(bipy)(H2O)] (4) and (Type-II): [ZnL1L2] (5), [ZnL1L2(py)] (6) and [ZnL1L2(bipy)] (7). The synthesized complexes were characterized in the solid state by FT-IR, CHN analyses and in solution state by NMR (1H, 13C) spectroscopy. Complexes 3 and 4 were also characterized by single crystal analysis where data revealed that the geometry around each Zn atom is distorted trigonal bipyramidal and octahedral, respectively. The synthesized complexes were interacted with SS-DNA and CTAB (surfactant). Interaction of the synthesized compounds with SS-DNA was studied by UV–visible spectroscopy and viscometry and intercalative mode of interaction was exhibited. Moreover, the interaction of the synthesized complexes with CTAB was studied by conductometry showing a strong binding that is evident from higher CMC and negative Gibbs free energy of micellization (ΔGm) values. The tested compounds were further screened for in vitro antibacterial and antifungal activities and were found active against the studied strains of bacteria and fungus.