Metal-free Ligand Research Articles

Computationally Guided Ligand Discovery from Compound Libraries and Discovery of a New Class of Ligands for Ni-Catalyzed Cross-Electrophile Coupling of Challenging Quinoline Halides.

Although screening technology has heavily impacted the fields of metal catalysis and drug discovery, its application to the discovery of new catalyst classes has been limited. The diversity of on- and off-cycle pathways, combined with incomplete mechanistic understanding, means that screens of potential new ligands have thus far been guided by intuitive analysis of the metal binding potential. This has resulted in the discovery of new classes of ligands, but the low hit rates have limited the use of this strategy because large screens require considerable cost and effort. Here, we demonstrate a method to identify promising screening directions via simple and scalable computational and linear regression tools that leads to a substantial improvement in hit rate, enabling the use of smaller screens to find new ligands. The application of this approach to a particular example of Ni-catalyzed cross-electrophile coupling of aryl halides with alkyl halides revealed a previously overlooked trend: reactions with more electron-poor amidine ligands result in a higher yield. Focused screens utilizing this trend were more successful than serendipity-based screening and led to the discovery of two new types of ligands, pyridyl oxadiazoles and pyridyl oximes. These ligands are especially effective for couplings of bromo- and chloroquinolines and isoquinolines, where they are now the state of the art. The simplicity of these models with parameters derived from metal-free ligand structures should make this approach scalable and widely accessible.

Synthesis, characterisation, and solution behaviour of Ag(I) bis(phenanthroline-oxazine) complexes and the evaluation of their biological activity against the pathogenic yeast Candida albicans

Three Ag(I) bis(phenanthroline-oxazine) complexes with varying lipophilicity were synthesised and characterised. The solution stoichiometry of 1:2 Ag(I):ligand was determined for each complex by the continuous variation Job’s plot method using NMR spectroscopy. NMR studies were also carried out to investigate the fluxional behaviour of the Ag(I) complexes in solution. The biological activity of the silver(I) complexes and the corresponding ligands towards a clinical strain of Candida albicans MEN was studied using broth microdilution assays. Testing showed the choice of media and the duration of incubation were key determinants of the inhibitory behaviour towards Candida albicans, however, the difference between freshly prepared and pre-prepared solutions was insignificant in minimal media. The activity of the metal-free ligands correlated with the length of the alkyl chain. In minimal media, the methyl ester phenanthroline-oxazine ligand was effective only at 60 μM, limiting growth to 67% of the control, while a 60 μM dose of the propyl ester analogue limited fungal growth at < 20% of the control. MIC50 and MIC80 values for the propyl and hexyl ester analogues were calculated to be 45 and 59 µM (propyl), and 18 and 45 µM (hexyl). Moreover, in a study of activity as a function of time it was observed that the hexyl ester ligand maintained its activity for longer than the methyl and propyl analogues; after 48 h a 60 μM dose held fungal growth at 24% of that of the control. Complexation to Ag(I) was much more effective in enhancing biological activity of the ligands than was increasing the ester chain length. Significantly no difference in activity between the three silver(I) complexes was observed under the experimental conditions. All three complexes were substantially more active than their parent ligands against Candida albicans and AgClO4 and the three silver(I) bis(phen-oxazine) complexes have MIC80 values of < 15 μM. The ability of the silver(I) complexes to hold fungal growth at about 20% of the control even after 48 h incubation at low dosages (15 μM) showcases their superiority over the simple silver(I) perchlorate salt, which ceased to be effective at dosages below 60 μM at the extended time point.

Hydrogenobinamide and nibinamide - Metal-free ligand and Ni(II)-analogue of the vitamin B12 precursor cobinamide

The replacement of cobalt in vitamin B[Formula: see text] derivatives by other transition metals is a formal path to non-natural corrins. Here, we describe nibinamide (Nibi), the novel Ni(II)-analogue of the natural B[Formula: see text]-derivative cobinamide (Cbi), and its synthesis from the metal-free ligand of Cbi, hydrogenobinamide (Hbi), both isolated as tetrafluoroborate salts. Aqueous solutions of the metal-free corrin Hbi are strongly fluorescent, whereas its Ni(II)-complex Nibi is non-luminescent. The solution structures of Hbi and of Nibi were characterized by hetero-nuclear NMR-spectroscopy. The Ni(II)-corrin Nibi was deduced to be roughly iso-structural to cob(I)inamide (Cbi[Formula: see text] and to house a diamagnetic d8-metal-ioniso-electronic to Co[Formula: see text] in Cbi[Formula: see text]. The chemically robust Nibi is, thus, a structural mimic of enzyme-activated and reduced biosynthetic precursors of vitamin B[Formula: see text] and a B[Formula: see text]-antimetabolite potentially functioning as a specific inhibitor of B[Formula: see text]-biosynthesis.

Dynamic Intramolecular Cap for Preserving Metallodrug Integrity─A Case of Catalytic Fluoroquinolones.

A library of eight new fluoroquinolone-nuclease conjugates containing a guanidinoethyl or aminoethyl auxiliary pendant on the cyclen moiety was designed and synthesized to investigate their potential for overcoming the general issue of "metallodrug vulnerability" under physiological conditions. The Cu(II) and Co(III) complexes of the new designer compounds were synthesized, and their potential to operate a dynamic, intramolecular cap with DNase activity was explored. The lead Co(III)-cyclen-ciprofloxacin conjugate showed excellent in vitro hydrolytic DNase activity, which was retained in the presence of strong endogenous chelators and exhibited enhanced antibacterial activity relative to the metal-free ligand (in the absence of any adjuvants), thereby demonstrating a "proof of concept" in vitro and ex vivo, respectively, for the dynamic cap hypothesis. The lead conjugate nicked supercoiled plasmid DNA within the fluoroquinolone-gyrase-DNA ternary complex and thereby disabled the function of gyrase, a new mode of action not previously reported for any fluoroquinolone.

Template Synthesis, Spectroscopic Characterization and Antimicrobial Studies of Oxovanadium(IV) Tetraazamacrocyclic Complexes Derived from 1, 8-Diaminonaphthalene and Substituted β-Diketones

A new series of oxovanadium (IV) tetraazamacrocyclic complexes of type [VO(mac)]SO4, have been synthesized via in situ reaction of 1,8-diaminonaphthalene and substituted β-diketones (1-phenyl-3-(phenyl/4-chlorophenyl/4-hydroxyphenyl/4- methoxyphenyl/4-nitrophenyl)-diketone) in the presence of oxovanadium(IV) sulphate in methanol. Attempts to synthesize the corresponding metal free macrocyclic ligands did not prove successful. Complexes were characterized on the basis of elemental analyses, conductance measurements, magnetic properties and spectral (electronic, IR, and EPR) data. The magnetic moments of the complexes lie in the range 1.70-1.78BM suitable for complexes with one unpaired electron and paramagnetic nature. The infrared spectra indicates that the ligands coordinate through four aza nitrogen atoms to vanadium(IV). The fluid solution EPR spectra show an eight-line pattern typical for a mononuclear VO(IV) complexes. The spectral studies support a square pyramidal geometry for the oxovanadium(IV) complexes. The oxovanadium complexes were tested for their antibacterial activity against bacteria Bacillus subtilis, Staphylococcus aureus, Escherichia coli and antifungal activity against fungi Aspergillus niger and Candida albicans. The complexes show moderate to good activity as compared to standard antibiotic tetracycline and the antifungal drug fluconazole.

New Homo and Heterobinuclear Macrocyclic Complexes Bearing Isatine Structural Characterization, Thermal Study and DFT Calculations

A new metal-free macrocyclic Schiff base ligand bearing two metal cavities incorporated with two sets of N3O2 donor atoms derived from 2, 6-diaminopyridine and isatine was synthesized. The new ligand was used to prepare homo and hetero binuclear macrocyclic Schiff base complexes with Ni (II), Cu (II), ZrO (II) and Ba (II) metal ions. The ligand and metal complexes were characterized using Fourier transform infrared (FT-IR), UV–vis, mass spectroscopy, elemental analysis (CHN), thermo gravimetric analysis (TGA), magnetic susceptibility, and molar conductivity measurements. The DFT calculations using the B3LYP functional method have been applied to obtain the geometry and electronic properties of the ligand and its metal complexes to support the experimental data. To describe the reactivity of the title molecules, the HOMO and LUMO levels and Mulliken atomic charges were determined.

Magnesium Phthalocyanines and Tetrapyrazinoporphyrazines: The Influence of a Solvent and a Delivery System on a Dissociation of Central Metal in Acidic Media.

Magnesium complexes of phthalocyanines (Pcs) and their aza-analogues have a great potential in medical applications or fluorescence detection. They are known to demetallate to metal-free ligands in acidic environments, however, detailed investigation of this process and its possible prevention is lacking. In this work, a conversion of lipophilic and water-soluble magnesium complexes of Pcs and tetrapyrazinoporphyrazines (TPyzPzs) to metal-free ligands was studied in relation to the acidity of the environment (organic solvent, water) including the investigation of the role of delivery systems (microemulsion or liposomes) in improvement in their acido-stability. The mechanism of the demetallation in organic solvents was based on an acidoprotolytic mechanism with the protonation of the azomethine nitrogen as the first step and a subsequent conversion to non-protonated metal-free ligands. In water, the mechanism seemed to be solvoprotolytic without any protonated intermediate. The water-soluble magnesium complexes were stable in a buffer with a physiological pH 7.4 while a time-dependent demetallation was observed in acidic pH. The demetallation was immediate at pH < 2 while the full conversion to metal-free ligand was done within 10 min and 45 min for TPyzPzs at pH 3 and pH 4, respectively. Incorporation of lipophilic magnesium complexes into microemulsion or liposomes substantially decreased the rate of the demetallation with the latter delivery system being much more efficient in the protection from the acidic environment. A comparison of two different macrocyclic cores revealed significantly higher kinetic inertness of magnesium TPyzPz complexes than their Pc analogues.

Highly Antiproliferative Latonduine and Indolo[2,3-c]quinoline Derivatives: Complex Formation with Copper(II) Markedly Changes the Kinase Inhibitory Profile.

A series of latonduine and indoloquinoline derivatives HL1–HL8 and their copper(II) complexes (1–8) were synthesized and comprehensively characterized. The structures of five compounds (HL6, [CuCl(L1)(DMF)]·DMF, [CuCl(L2)(CH3OH)], [CuCl(L3)]·0.5H2O, and [CuCl2(H2L5)]Cl·2DMF) were elucidated by single crystal X-ray diffraction. The copper(II) complexes revealed low micro- to sub-micromolar IC50 values with promising selectivity toward human colon adenocarcinoma multidrug-resistant Colo320 cancer cells as compared to the doxorubicin-sensitive Colo205 cell line. The lead compounds HL4 and 4 as well as HL8 and 8 induced apoptosis efficiently in Colo320 cells. In addition, the copper(II) complexes had higher affinity to DNA than their metal-free ligands. HL8 showed selective inhibition for the PIM-1 enzyme, while 8 revealed strong inhibition of five other enzymes, i.e., SGK-1, PKA, CaMK-1, GSK3β, and MSK1, from a panel of 50 kinases. Furthermore, molecular modeling of the ligands and complexes showed a good fit to the binding pockets of these targets.

Synthesis, molecular docking, molecular dynamic, quantum calculation, and antibacterial activity of new Schiff base-metal complexes

The transition metals Co(II) and Cu(II) metal containing Schiff base-metal complexes are highly biological significance molecule for antimicrobial activity, as a result this study has been designed for investigation the synthesis, characterization, in vitro evaluation and in sillico study with molecular dynamic. To kick off, the new Schiff base free ligands, such as L1 and L2, were synthesized from the condensation of nicotinic acid carbohydrazide with vanillin or 2-chloroquinoline-3-carbaldehyde, respectively. The chemical structure of the synthesized Schiff base ligands, and their metal complexes have confirmed their structural geometry by spectroscopic analysis, such as 1H NMR, FTIR and UV-visible spectra, as well as confirming their chemical conversion (4-7) by metalation with the transition metals Co(II) and Cu(II). For evaluation the In vitro study, the antibacterial activity has screened against four human pathogenic bacteria. In addition, for developing the theoretical evaluation of the quantum calculation and biological activity, computational tools were used through the Density Functional Theory (DFT), molecular docking, molecular dynamics and ADMET study. It has revealed that the metal complexes (4-7) illustrate the higher antibacterial activity than the metal free ligands (1-2). The highest antibacterial activity conveys against P. vulgaris among E. coli, S. aureus and B. subtilis through disc diffusion method, and it is near to the standard (Gentamycin) for P. vulgaris. Next, the binding affinity of molecular docking study is more than −6.0 kcal/mol, while the L1-Co (4) shows the highest binding affinity among all bacterial pathogens. The molecular dynamics confirms their ligand-protein complex stability with high range of time (50 ns). Moreover, the Lipinski rule and ADMET properties were evaluated. Finally, the Cobalt complex {L1-Co (4)} shows the higher biological activity in views of both in vitro and computational study.

Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition.

Three new thiosemicarbazones (TSCs) HL1–HL3 as triapine analogues bearing a redox-active phenolic moiety at the terminal nitrogen atom were prepared. Reactions of HL1–HL3 with CuCl2·2H2O in anoxic methanol afforded three copper(II) complexes, namely, Cu(HL1)Cl2 (1), [Cu(L2)Cl] (2′), and Cu(HL3)Cl2 (3), in good yields. Solution speciation studies revealed that the metal-free ligands are stable as HL1–HL3 at pH 7.4, while being air-sensitive in the basic pH range. In dimethyl sulfoxide they exist as a mixture of E and Z isomers. A mechanism of the E/Z isomerization with an inversion at the nitrogen atom of the Schiff base imine bond is proposed. The monocationic complexes [Cu(L1–3)]+ are the most abundant species in aqueous solutions at pH 7.4. Electrochemical and spectroelectrochemical studies of 1, 2′, and 3 confirmed their redox activity in both the cathodic and the anodic region of potentials. The one-electron reduction was identified as metal-centered by electron paramagnetic resonance spectroelectrochemistry. An electrochemical oxidation pointed out the ligand-centered oxidation, while chemical oxidations of HL1 and HL2 as well as 1 and 2′ afforded several two-electron and four-electron oxidation products, which were isolated and comprehensively characterized. Complexes 1 and 2′ showed an antiproliferative activity in Colo205 and Colo320 cancer cell lines with half-maximal inhibitory concentration values in the low micromolar concentration range, while 3 with the most closely related ligand to triapine displayed the best selectivity for cancer cells versus normal fibroblast cells (MRC-5). HL1 and 1 in the presence of 1,4-dithiothreitol are as potent inhibitors of mR2 ribonucleotide reductase as triapine.

Coumarin-Based Triapine Derivatives and Their Copper(II) Complexes: Synthesis, Cytotoxicity and mR2 RNR Inhibition Activity.

A series of thiosemicarbazone-coumarin hybrids (HL1-HL3 and H2L4) has been synthesised in 12 steps and used for the preparation of mono- and dinuclear copper(II) complexes, namely Cu(HL1)Cl2 (1), Cu(HL2)Cl2 (2), Cu(HL3)Cl2 (3) and Cu2(H2L4)Cl4 (4), isolated in hydrated or solvated forms. Both the organic hybrids and their copper(II) and dicopper(II) complexes were comprehensively characterised by analytical and spectroscopic techniques, i.e., elemental analysis, ESI mass spectrometry, 1D and 2D NMR, IR and UV–vis spectroscopies, cyclic voltammetry (CV) and spectroelectrochemistry (SEC). Re-crystallisation of 1 from methanol afforded single crystals of copper(II) complex with monoanionic ligand Cu(L1)Cl, which could be studied by single crystal X-ray diffraction (SC-XRD). The prepared copper(II) complexes and their metal-free ligands revealed antiproliferative activity against highly resistant cancer cell lines, including triple negative breast cancer cells MDA-MB-231, sensitive COLO-205 and multidrug resistant COLO-320 colorectal adenocarcinoma cell lines, as well as in healthy human lung fibroblasts MRC-5 and compared to those for triapine and doxorubicin. In addition, their ability to reduce the tyrosyl radical in mouse R2 protein of ribonucleotide reductase has been ascertained by EPR spectroscopy and the results were compared with those for triapine.

Aggregation of water soluble octaanionic phthalocyanines and their photoinactivation antimicrobial effect in vitro

Aggregation of sulfophenylsulfanyl-substituted phthalocyanine and its aluminum complex has been investigated in aqueous solutions of DMF or nonionic surfactant Tween 80 by UV-VIS spectroscopy and DLS. Aluminum complex is less aggregated and 4.5 orders of magnitude stronger bound to the micelles of Tween 80 compared to a metal-free ligand. Under irradiation the phthalocyanine derivatives reveal a pronounced antimicrobial activity towards both Gram(+) and Gram(−) archive microflora in vitro.

Abstract 1939: Improved activity and paraptosis-induction of anticancer thiosemicarbazones requires high copper(II) complex stability and slow reduction kinetics

Abstract Triapine, which is currently tested in a clinical phase III trial, is the best-studied thiosemicarbazone (TSC) for anticancer therapy. With regard to the mode of action, anticancer activity of TSCs is frequently linked to their ability to chelate essential metal ions such as copper and iron. As Triapine monotherapy showed promising results mainly against hematological diseases, novel TSC derivatives have been developed and clinically investigated for their activity against solid tumors. These novel TSCs belong to a subclass with enhanced anticancer activity in vitro and in vivo which were recently discovered to induce paraptosis, a form of programmed but caspase-independent cell death. As these TSCs are characterized by a up to 1000-fold higher activity in cell culture compared to Triapine, the aim of this study was to elucidate the mechanism of action as well as the underlying structural and chemical requirements of these effects. For this purpose, a panel of structurally related Triapine derivatives was examined for anticancer activity (as metal-free ligand and copper(II) complex), paraptosis-inducing potential as well as solution stability and redox properties of their copper(II) complexes. Correlation studies between these chemical and biological properties revealed that the increased anticancer activity and paraptosis-inducing potential of the nanomolar active TSCs is related to a higher copper(II) complex solution stability and slower reduction rate. Unexpectedly, the TSCs with lower activity produced higher superoxide levels in a cell-free setting. This paradox could be explained by their lower copper(II) complex stability and increased readiness to be reduced, which resulted in a fast reduction of intracellular complexes and release of the metal-free ligand. Although this process resulted in the generation of superoxide, cell damage seemed to be prevented by rapid upregulation of the superoxide dismutase (in vitro and in vivo). In contrast, the copper complexes of the highly active TSCs are stable enough to reach intracellular targets such as the ER-resident protein disulfide isomerase, whose inhibition is crucial for paraptosis induction by TSCs. In conclusion, copper complex stability is a crucial parameter of TSC activity, influencing the (intracellular) formation or dissociation of copper complexes. This intracellular stability of complexes, affects their mechanism of action as well as cell death induction. Overall, this study points out the importance of the redox parameters in order to understand and predict the TSC anticancer activity as well as their mechanism of action and, thereby, will pave the way for the development of improved anticancer agents. Citation Format: Sonja Hager, Veronika F. Pape, Vivien Pósa, Bianca Montsch, Lukas Uhlik, Gergely Szakàcs, Szilárd Tóth, Nikolett Jabronka, Bernhard K. Keppler, Walter Berger, Christian R. Kowol, Éva A. Enyedy, Petra Heffeter. Improved activity and paraptosis-induction of anticancer thiosemicarbazones requires high copper(II) complex stability and slow reduction kinetics [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1939.

Metal-Salen-based Probes for the Selective Detection of Phosphates via a Disassembly Approach.

Polyoxophosphates are ubiquitous in nature and play important roles in biological systems and in the environment. Pyrophosphate (PPi), an important member of this family, is produced in over 200 biochemical reactions and is a marker in clinical diagnosis. In addition to its endogenous role, PPi alias E450 is currently used as preservative, emulsifier or taste intensifier in foodstuff. Despite this widespread occurrence and biological importance, it is rather surprising that robust chemical systems that detect selectively and sensitively PPi in challenging matrices are still lacking. This mini review focuses on metal-salen complexes as reaction-based fluorescent sensors for the selective detection of PPi and other phosphates. The mode of detection is based on a novel disassembly approach in which the metal ion is sequestered by the target analyte from the complex and the metal-free ligand hydrolyses spontaneously into its fluorescent subunits. Optimizations of the probe and applications for PPi detection in cells and foodstuff are described.

Light-driven coordination anions-directed regulation of chromism in three metal complexes assembled by cyano-equipped dithienylethene ligand

Three coordination compounds were self-assembled successfully with Ag(I) ions and photo-responsive ligands featuring a cyano-equipped dithienylethene unit. Anions with different coordinating abilities were selected to construct distinct topologies, which are evidenced by X-ray crystallographic analysis. CF3 COO− and CF3 SO3− are involved into coordination in 1 and 3, respectively, whereas in 2 BF4− present merel y as ionic guests counterbalancing the framework charge. Anions also show their subtle effects on coordinated atoms, interactions, and ligand configurations. The quite different structures of 1–3 indicate an interesting anion-directed structural self-assembly.Followed examinations on photochromism illustrated that the reversible photo-isomerizations of three complexes are all retained after complexzation with Ag(I) center. Various degrees of bathochromic shifts in absorptions were observed as compared with that of the metal-free ligand. Therefore, the photo-switching of these compounds could be modulated conveniently and finely by varying simply the coordination anions and then triggering by light irradiation. The discussions of structure-properties relationship concluded that anions exert their effects on coordination structure through adjusting the configurations of ligands in complexes. Strong coordinating anions facilitate a pronounced conformational change of ligand whereas un-coordinating anion leads to smaller variation. The distinct structural changes of ligand result finally the different perturbation of photochromic behavior.

Synthesis, antiproliferative activity and mechanism of copper(II)-thiosemicarbazone complexes as potential anticancer and antimicrobial agents

Malignant tumors have become one of the challenges to global human health today, and the development of new drugs has become a research hotspot for tumor treatment. In order to prove that copper(II)-thiosemicarbazone complexes can be used as antibacterial and antitumor agents, we have synthesized and characterized three copper(II) complexes (C1-C3). These Cu(II) complexes exhibited excellent anticancer and antimicrobial activity, and greatly exceed the corresponding metal-free ligands. C3 has the highest anti-proliferative activity (0.20 ± 0.04 µM) against A549 (human lung carcinoma cell lines) and the best inhibitory zone diameter (25.78 ± 0.18 mm) against E. coli. The lipophilicity of the ligand is closely related to the anti-proliferative and antibacterial activities of these Cu(II) complexes. The study of the cellular mechanism demonstrates that these Cu(II) complexes promoted cell apoptosis by catalyzing hydrogen peroxide to produce intracellular reactive oxygen species (ROS). Antibacterial experiments showed that these Cu(II) complexes exhibited potent antibacterial activities, especially against gram-negative bacteria. These Cu(II) complexes may initially cause outer membrane/lipopolysaccharide (LPS) instability, disrupt cell membranes, and ultimately lead to bacterial cell lysis.

Two novel bipyridine-based cobalt (II) complexes: synthesis, characterization, molecular docking, DNA-binding and biological evaluation

Bipyridine derivatives have shown different applications in chemistry such as electron transfer, catalysis, biological systems and artificial photosynthesis. Two cobalt(II) complexes with formula [Co(5,5′-dmbipy)2(NCS)2]1 and [Co(5,5′-dmbipy)3] [Co(NCS)4]2 were prepared. The metal complexes 1 and 2 were characterized through FT-IR, electronic absorption, elemental analysis and 1H-NMR. The interaction of complexes 1 and 2 with FS-DNA was investigated by fluorescence, UV–Vis and gel electrophoresis. The antibacterial properties have been studied in vitro against two gram-negative and two gram-positive standard bacterial strains. The synthesized complexes were further investigated against MCF-7 cells at 25, 50, 100 and 200 µM. The results revealed that the metal complexes can bind effectively to FS-DNA. The measured thermodynamic factors (ΔH°, ΔS° and ΔG°) displayed that hydrogen bonding, van der Waals forces (for DNA-compound 1) and electrostatic binding (for DNA-compound 2) are the most important interactions. The binding forces in metal complexes 1 and 2 are spontaneous as suggested by the negative ΔG°. Specific viscosity of FS-DNA remained without significant changes while the concentration of complexes 1 and 2 increased. The results of molecular docking with FS-DNA illustrate the binding sites and binding modes that are in acceptable agreement with experimental results. The biological results determined that complexes 1 and 2 exhibit antibacterial activities that are better than those shown for their corresponding metal salt and free ligand. The target compounds showed low-to-moderate cytotoxicity activities. The obtained results revealed that the synthesized complexes are stronger antibacterial agents against the gram-positive than gram-negative bacteria. In the present study, for the first time we reported two Co(II) complexes bearing 5,5′-dimethyl-2,2′-bipyridine ligands.Communicated by Ramaswamy H. Sarma

Synthesis, Structure, and Biological Assays of Novel Trifluoromethyldiazepine–Metal Complexes

A new series of CuII, NiII, CoII, and MnIII complexes have been synthesised from the (6Z)-6-(7-trifluoromethyl-1,2,3,4-tetrahydro-5H-1,4-diazepin-5-ylidene)cyclohexa-2,4-dien-1-one (HDZP) ligand. These complexes were characterised by elemental, spectroscopic (IR and UV-vis), and thermal analysis. The crystal structure of Cu-DZP was solved by X-ray diffraction methods. The complex crystallises in the monoclinic P21/c space group, with two molecules per unit cell. The crystal lattice is stabilised by different intra and intermolecular interactions. Hirshfeld surface analysis was employed to obtain additional information about interactions that are responsible for the crystal packing. Quantitative examination of the fingerprint plots indicated the dominant contribution of H⋯H and H⋯X (X=O, F) interactions in the crystal packing. In addition, C–H⋯chelate ring (CR) and C–H⋯π interactions are described in detail and evaluated using DFT calculations. The antibacterial properties and the mechanism of inhibition of the main bacterial resistant mechanism, the biofilm, of the metal complexes and free ligand were investigated. [Mn(DZP)3]·2H2O was the most active complex against the Pseudomonas aeruginosa biofilm formation with an inhibition of 40%. However, none of the complexes inhibit more than 25% of the Gram negative bacteria microbial development. The most meaningful result was the bactericidal effect of [Co(DZP)2(H2O)2]·2H2O against the Gram positive bacteria, Staphylococcus aureus, which inhibits the bacterial development and significantly reduces the biofilm formation at low concentration.

Transition metal complexes of α-aminophosphonates part II: Synthesis, spectroscopic characterization, and in vitro anticancer activity of copper(II) complexes of α-aminophosphonates

A one pot procedure was used to synthesize two new derivatives of α-aminophosphonates. Novel copper(II) complexes of α-aminophosphonates were synthesized by coordinating different copper salts with the newly synthesized α-aminophosphonates. Their structures were characterized by different spectral and analytical techniques. Evaluation of the metal-free ligands HL1, HL2, and their Cu(II) complexes against human colon carcinoma HT-29 cell lines was performed, using cisplatin as a reference drug. The results indicated that the complexes of the ligand HL1 exhibited enhanced anticancer activity, while ligand HL2 complexes showed decreased anticancer activity.

Synthesis and spectroscopic properties of axial phenoxide and para amino phenoxide incorporated indium (III) porphyrins

Tetrakis-4-methoxyphenyl indium(III) porphyrins containing phenolic and para amino phenolic moieties in the apical sites have been successfully prepared and characterized spectroscopically. The phases and structure evolutions of prepared porphyrins were deduced from powder X-ray diffraction (PXRD). The axial coordination of phenolic moieties induces slight shift of the 1H NMR signals of indium porphyrin macrocycles. The measurements of UV–Visible absorptions of porphyrins in CH2Cl2 and CH3COOC2H5 reflects that axially ligated metal chelates at neutral pH display hyperchromicity of absorption bands compared to unligated metal porphyrin. The most striking feature was the structural stability of indium porphyrins under basic (pH = 10) as well as acidic media (pH = 4). On the other hand, the metal free ligand 5, 10, 15, 20-Tetrakis-(4-methoxyphenyl) porphyrin, H2TMP (I) undergoes J type aggregation in acidic media (pH = 4). The robustness of indium porphyrins especially in acidic media are in strong contrary to other sitting atop (SAT) or out of plane (OOP) complexes which are usually demetallized under acidic pH. All the prepared macro rings exhibit negative solvatochromism reflected by the blue shift of absorption bands in CH3COOC2H5 (more polar) than in CH2Cl2 (less polar). The photoluminescence emissions in indium(III) species are significantly quenched relative to metal free ligand (I) due to internal heavy atom effect and distortion of ligand plane. The quenching of fluorescence bands are more pronounced in axially ligated metal porphyrins. The lesser excited state lifetimes of indium(III) porphyrins relative to free base analog (I) may be ascribed to spin orbit coupling induced by indium(III) ion in the respective metal chelates.