Coordinative Compounds Based on Unsaturated Carboxylate with Versatile Biological Applications.

This review presents an overview of the biological applications of coordinative compounds based on unsaturated carboxylates accompanied by other ligands, usually N-based heterocyclic species. The interest in these compounds arises from the valuable antimicrobial and antitumor activities evidenced by some species, as well as from their ability to generate metal-containing polymers suitable for various medical purposes. Therefore, we describe the recently discovered aspects related to the synthesis, structure, and biological activity of a wide range of unsaturated carboxylate-containing species and metal ions, originating mostly from 3d series. The unsaturated carboxylates encountered in coordinative compounds are acrylate, methacrylate, fumarate, maleate, cinnamate, ferulate, coumarate, and itaconate. Regarding the properties of the investigated compounds, it is worth mentioning the good ability of some to inhibit the development of resistant strains or microbial biofilms on inert surfaces or, even more, exert antitumor activity against resistant cells. The ability of some species to intercalate into DNA strands as well as to scavenge ROS species is also addressed.

Decavanadate-Bearing Guanidine Derivatives Developed as Antimicrobial and Antitumor Species.

To obtain biologically active species, a series of decavanadates (Hpbg)4[H2V10O28]·6H2O (1) (Htbg)4[H2V10O28]·6H2O; (2) (Hgnd)2(Hgnu)4[V10O28]; (3) (Hgnu)6[V10O28]·2H2O; and (4) (pbg = 1-phenyl biguanide, tbg = 1-(o-tolyl)biguanide, gnd = guanidine, and gnu = guanylurea) were synthesized and characterized by several spectroscopic techniques (IR, UV-Vis, and EPR) as well as by single crystal X-ray diffraction. Compound (1) crystallizes in space group P-1 while (3) and (4) adopt the same centrosymmetric space group P21/n. The unusual signal identified by EPR spectroscopy was assigned to a charge-transfer π(O)→d(V) process. Both stability in solution and reactivity towards reactive oxygen species (O2- and OH·) were screened through EPR signal modification. All compounds inhibited the development of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis bacterial strains in a planktonic state at a micromolar level, the most active being compound (3). However, the experiments conducted at a minimal inhibitory concentration (MIC) indicated that the compounds do not disrupt the biofilm produced by these bacterial strains. The cytotoxicity assayed against A375 human melanoma cells and BJ human fibroblasts by testing the viability, lactate dehydrogenase, and nitric oxide levels indicated compound (1) as the most active in tumor cells.

An Interesting Conversion Route of Mononuclear Zinc Complex to Zinc Mixed Carboxylate Coordination Polymer.

A complex [Zn(bpy)(acr)2]·H2O (1) was converted in a DMF medium (DMF = N,N'-dimethylformamide) into a coordination polymer [Zn(bpy)(acr)(HCOO)]n (1a) (bpy = 2,2'-bipyridine, and Hacr = acrylic acid), and the species was fully characterized through a single crystal X-ray diffraction. Additional data were obtained by IR and thermogravimetric analysis. Complex (1a) crystalized the coordination polymer in the space group Pca21 of an orthorhombic system. Structural characterization revealed that Zn(II) adopted a square pyramidal stereochemistry generated by bpy molecules, coordinated by chelate, acrylate, and formate ions as unidentate and bridged, respectively. The presence of both the formate and the acrylate with different coordination modes generated two bands in ranges that were characteristic for the carboxylate vibration modes. Thermal decomposition occurs in two complex steps: it first happens via a bpy release, which is followed by an overlapped process that is associated with acrylate and formate decomposition. The obtained complex is of present interest due to the presence of two different carboxylates in its composition and situation, which is rarely reported in the literature.

Copper (II) Species with Improved Anti-Melanoma and Antibacterial Activity by Inclusion in ß-Cyclodextrin.

To improve their biological activity, complexes [Cu(bipy)(dmtp)2(OH2)](ClO4)2·dmtp (1) and [Cu(phen)(dmtp)2(OH2)](ClO4)2·dmtp (2) (bipy 2,2'-bipyridine, phen: 1,10-phenantroline, and dmtp: 5,7-dimethyl-1,2,4-triazolo [1,5-a]pyrimidine) were included in ß-cyclodextrins (ß-CD). During the inclusion, the co-crystalized dmtp molecule was lost, and UV-Vis spectra together with the docking studies indicated the synthesis of new materials with 1:1 and 1:2 molar ratios between complexes and ß-CD. The association between Cu(II) compounds and ß-CD has been proven by the identification of the components' patterns in the IR spectra and powder XRD diffractograms, while solid-state UV-Vis and EPR spectra analysis highlighted a slight modification of the square-pyramidal stereochemistry around Cu(II) in comparison with precursors. The inclusion species are stable in solution and exhibit the ability to scavenge or trap ROS species (O2·- and HO·) as indicated by the EPR experiments. Moreover, the two inclusion species exhibit anti-proliferative activity against murine melanoma B16 cells, which has been more significant for (2)@ß-CD in comparison with (2). This behavior is associated with a cell cycle arrest in the G0/G1 phase. Compared with precursors, (1a)@ß-CD and (2a)@ß-CD exhibit 17 and 26 times more intense activity against planktonic Escherichia coli, respectively, while (2a)@ß-CD is 3 times more active against the Staphylococcus aureus strain.

Zinc(II) Carboxylate Coordination Polymers with Versatile Applications.

This review considers the applications of Zn(II) carboxylate-based coordination polymers (Zn-CBCPs), such as sensors, catalysts, species with potential in infections and cancers treatment, as well as storage and drug-carrier materials. The nature of organic luminophores, especially both the rigid carboxylate and the ancillary N-donor bridging ligand, together with the alignment in Zn-CBCPs and their intermolecular interaction modulate the luminescence properties and allow the sensing of a variety of inorganic and organic pollutants. The ability of Zn(II) to act as a good Lewis acid allowed the involvement of Zn-CBCPs either in dye elimination from wastewater through photocatalysis or in pathogenic microorganism or tumor inhibition. In addition, the pores developed inside of the network provided the possibility for some species to store gaseous or liquid molecules, as well as to deliver some drugs for improved treatment.

A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies.

"Drug repositioning" is a modern strategy used to uncover new applications for out-of-date drugs. In this context, nalidixic acid, the first member of the quinolone class with limited use today, has been selected to obtain nine new metal complexes with lanthanide cations (La3+, Sm3+, Eu3+, Gd3+, Tb3+); the experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms, findings that are supported by DFT calculations. The cytotoxic activity of the complexes has been studied using the tumoral cell lines, MDA-MB-231 and LoVo, and a normal cell line, HUVEC. The most active compounds of the series display selective activity against LoVo. Their affinity for DNA and the manner of binding have been tested using UV-Vis spectroscopy and competitive binding studies; our results indicate that major and minor groove binding play a significant role in these interactions. The affinity towards serum proteins has also been evaluated, the complexes displaying higher affinity towards albumin than apotransferrin.

Antiproliferative Copper(II) Complexes Bearing Mixed Chelating Ligands: Structural Characterization, ROS Scavenging, In Silico Studies, and Anti-Melanoma Activity.

Melanoma is a skin cancer characterized by rapid growth and spread for which current therapies produce both resistance and increased risk of infection. To develop new anti-melanoma biocompatible species, the series of complexes Cu(N-N)(bzac)(X)⋅nH2O (N-N: 1,10-phenanthroline/2,2'-bipyridine, Hbzac: 1-phenyl-1,3-butanedione, X: NO3/ClO4, and n = 0, 1) was studied. Single-crystal X-ray diffraction revealed a mononuclear structure for all complexes. The ability of the complexes to scavenge or trap reactive oxygen species such as O2⋅- and HO⋅ was proved by EPR spectroscopy experiments. All complexes inhibited B16 murine melanoma cells in a dose-dependent and nanomolar range, but the complexes with 1,10-phenanthroline were more active. Moreover, comparative activity on B16 and healthy BJ cells revealed a therapeutic index of 1.27-2.24. Bioinformatic methods were used to calculate the drug-likeness, pharmacokinetic, pharmacogenomic, and pharmacodynamic profiles of the compounds. The results showed that all compounds exhibit drug-likeness features, as well as promising absorption, distribution, metabolism, and excretion (ADME) properties, and no toxicity. The pharmacodynamics results showed that the neutral species appear to be good candidates for antitumor molecular targets (Tyrosyl-DNA phosphodiesterase 1, DNA-(apurinic or apyrimidinic site) lyase or Kruppel-like factor 5). Furthermore, the pharmacogenomic results showed a good affinity of the copper(II) complexes for the human cytochrome. These results recommend complexes bearing 1,10-phenanthroline as good candidates for developing drugs to melanoma alternative treatment.

Synthesis and Characterization of Hematite-Based Nanocomposites as Promising Catalysts for Indigo Carmine Oxidation.

The hematite-based nanomaterials are involved in several catalytic organic and inorganic processes, including water decontamination from organic pollutants. In order to develop such species, a series of bimetallic hematite-based nanocomposites were obtained by some goethite composites-controlled calcination. Their composition consists of various phases such as α-FeOOH, α-Fe2O3 or γ-Fe2O3 combined with amorphous (Mn2O3, Co3O4, NiO, ZnO) or crystalline (CuO) oxides of the second transition ion from the structure. The component dimensions, either in the 10-30 or in the 100-200 nm range, together with the quasi-spherical or nanorod-like shapes, were provided by Mössbauer spectroscopy and powder X-ray diffraction as well as transmission electron microscopy data. The textural characterization showed a decrease in the specific area of the hematite-based nanocomposites compared with corresponding goethites, with the pore volume ranging between 0.219 and 0.278 cm3g-1. The best catalytic activity concerning indigo carmine removal from water in hydrogen peroxide presence was exhibited by a copper-containing hematite-based nanocomposite sample that reached a dye removal extent of over 99%, which correlates with both the base/acid site ratio and pore size. Moreover, Cu-hbnc preserves its catalytic activity even after four recyclings, when it still reached a dye removal extent higher than 90%.

Metal Complexes-A Promising Approach to Target Biofilm Associated Infections.

Microbial biofilms are represented by sessile microbial communities with modified gene expression and phenotype, adhered to a surface and embedded in a matrix of self-produced extracellular polymeric substances (EPS). Microbial biofilms can develop on both prosthetic devices and tissues, generating chronic and persistent infections that cannot be eradicated with classical organic-based antimicrobials, because of their increased tolerance to antimicrobials and the host immune system. Several complexes based mostly on 3D ions have shown promising potential for fighting biofilm-associated infections, due to their large spectrum antimicrobial and anti-biofilm activity. The literature usually reports species containing Mn(II), Ni(II), Co(II), Cu(II) or Zn(II) and a large variety of multidentate ligands with chelating properties such as antibiotics, Schiff bases, biguanides, N-based macrocyclic and fused rings derivatives. This review presents the progress in the development of such species and their anti-biofilm activity, as well as the contribution of biomaterials science to incorporate these complexes in composite platforms for reducing the negative impact of medical biofilms.

Insights into Structure and Biological Activity of Copper(II) and Zinc(II) Complexes with Triazolopyrimidine Ligands.

In an attempt to increase the biological activity of the 1,2,4-triazolo[1,5-a]pyrimidine scaffold through complexation with essential metal ions, the complexes trans-[Cu(mptp)2Cl2] (1), [Zn(mptp)Cl2(DMSO)] (2) (mptp: 5-methyl-7-phenyl-1,2,4-triazolo[1,5-a]pyrimidine), [Cu2(dmtp)4Cl4]·2H2O (3) and [Zn(dmtp)2Cl2] (4) (dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine), were synthesized and characterized as new antiproliferative and antimicrobial species. Both complexes (1) and (2) crystallize in the P21/n monoclinic space group, with the tetrahedral surroundings generating a square-planar stereochemistry in the Cu(II) complex and a tetrahedral stereochemistry in the Zn(II) species. The mononuclear units are interconnected in a supramolecular network through π-π interactions between the pyrimidine moiety and the phenyl ring in (1) while supramolecular chains resulting from C-H∙∙∙π interactions were observed in (2). All complexes exhibit an antiproliferative effect against B16 tumor cells and improved antibacterial and antifungal activities compared to the free ligands. Complex (3) displays the best antimicrobial activity against all four tested strains, both in the planktonic and biofilm-embedded states, which can be correlated to its stronger DNA-binding and nuclease-activity traits.

Biological Activity of Triazolopyrimidine Copper(II) Complexes Modulated by an Auxiliary N-N-Chelating Heterocycle Ligands.

Novel complexes of type [Cu(N-N)(dmtp)2(OH2)](ClO4)2·dmtp ((1) N-N: 2,2'-bipyridine; (2) L: 1,10-phenantroline and dmtp: 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine) were designed in order to obtain biologically active compounds. Complexes were characterized as mononuclear species that crystallized in the space group P-1 of the triclinic system with a square pyramidal geometry around the copper (II). In addition to the antiproliferative effect on murine melanoma B16 cells, complex (1) exhibited low toxicity on normal BJ cells and did not affect membrane integrity. Complex (2) proved to be a more potent antimicrobial in comparison with (1), but both compounds were more active in comparison with dmtp-both against planktonic cells and biofilms. A stronger antimicrobial and antibiofilm effect was noticed against the Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). Both electron paramagnetic resonance (EPR) and Saccharomyces cerevisiae studies indicated that the complexes were scavengers rather than reactive oxygen species promoters. Their DNA intercalating capacity was evidenced by modifications in both absorption and fluorescence spectra. Furthermore, both complexes exhibited nuclease-like activity, which increased in the presence of hydrogen peroxide.

Antiproliferative and antibacterial properties of biocompatible copper(II) complexes bearing chelating N,N-heterocycle ligands and potential mechanisms of action.

In an attempt to propose new applications for the biomedical field, complexes with mixed ligands {[Cu(bpy)2(µ2OClO3)]ClO4}n (1) and [Cu(phen)2(OH2)](ClO4)2 (2) (bpy: 2,2'-biyridine; phen and 1,10-phenantroline) were evaluated for their antibacterial and cytotoxicicity features and for the elucidation of some of the mechanisms involved. Complex (2) proved to be a very potent antibacterial agent, exhibing MIC and MBEC values 2 to 54 times lower than those obtained for complex (1) against both susceptible or resistant Gram-positive and Gram-negative strains, in planktonic or biofilm growth state. In exchange, complex (1) exhibited selective cytotoxicity against melanoma tumor cells (B16), proving a promising potential for developing novel anticancer drugs. The possible mechanisms of both antimicrobial and antitumor activity of the copper(II) complexes is their DNA intercalative ability coupled with ROS generation. The obtained results recommend the two complexes for further development as multipurpose copper-containing drugs.

Soft synthesis and characterization of goethite-based nanocomposites as promising cyclooctene oxidation catalysts.

Goethite based nanocomposites with a different composition such as 6FeO(OH)·MnO(OH)·0.5H2O (Mn-composite), xFeO(OH)·M(OH)2·yH2O (Co-composite (M: Co, x = 12, y = 3), Ni-composite (M: Ni, x = 7, y = 2)) and xFeO(OH)·MO·yH2O (Cu-composite (M: Cu, x = 5.5, y = 3), Zn-composite (M: Zn, x = 6, y = 1.5)) have been prepared by a soft chemical synthesis consisting in acetate hydrolysis. The data provided by Fourier transform infrared (FTIR), ultraviolet-visible-near infrared (UV-Vis-NIR), electron paramagnetic resonance (EPR) and Mössbauer spectra account for a slight modification of all composites' physicochemical properties compared to the starting material. Powder X-ray diffraction and transmission electron microscopy (TEM) investigations revealed the secondary phase nature and presence along with that of goethite. The TEM data are also consistent with a nano rod-like morphology with a 5-10 nm width and an average length of 40 nm. The catalytic oxidation of cyclooctene with O2 using isobutyraldehyde as reductant and acetonitrile as a solvent was performed in batch conditions for 5 h at room temperature. The selectivity for the epoxide was higher than 99% for all tested solids. The conversion of cyclooctene decreased from 55% to 4% following the same order of variance as the base/acid sites ratio: Mn-composite > Fe-composite > Co-composite > Ni-composite > Zn-composite > Cu-composite. The 6FeO(OH)·MnO(OH)·0.5H2O (Mn-composite) exhibited the most promising catalytic activity in cyclooctene oxidation, which can be correlated with the redox ability of Mn(iii) combined with the increased base character of this solid. The catalytic activity of this sample decreases by 10% after several successive reaction cycles.

Improvement in the Pharmacological Profile of Copper Biological Active Complexes by Their Incorporation into Organic or Inorganic Matrix.

Every year, more Cu(II) complexes are proven to be biologically active species, but very few are developed as drugs or entered in clinical trials. This is due to their poor water solubility and lipophilicity, low stability as well as in vivo inactivation. The possibility to improve their pharmacological and/or oral administration profile by incorporation into inorganic or organic matrix was studied. Most of them are either physically encapsulated or conjugated to the matrix via a moiety able to coordinate Cu(II). As a result, a large variety of species were developed as delivery carriers. The organic carriers include liposomes, synthetic or natural polymers or dendrimers, while the inorganic ones are based on carbon nanotubes, hydrotalcite and silica. Some hybrid organic-inorganic materials based on alginate-carbonate, gold-PEG and magnetic mesoporous silica-Schiff base were also developed for this purpose.

New Cobalt (II) Complexes with Imidazole Derivatives: Antimicrobial Efficiency against Planktonic and Adherent Microbes and In Vitro Cytotoxicity Features.

Three novel Co(II) complexes of the type [Co(C4H5O2)2L2] (where C4H5O2 is methacrylate anion; L = C3H4N2 (imidazole; HIm) (1), C4H6N2 (2-methylimidazole; 2-MeIm) (2), C5H8N2 (2-ethylimidazole; 2-EtIm) (3)) have been synthesized and characterized by elemental analysis, IR and UV-Vis spectroscopic techniques, thermal analysis and single crystal X-ray diffraction. X-ray crystallography revealed for complexes (1) and (2) distorted trigonal bipyramid stereochemistry for Co(II), meanwhile for complex (3) evidenced that the unit cell comprises three molecular units with interesting structural features. In each unit, both stereochemistry adopted by metallic ion and coordination modes of carboxylate anions are different. The screening of antimicrobial activity revealed that Candida albicans planktonic cells were the most susceptible, with minimal inhibitory concentration (MIC) values of 7.8 µg/mL for complexes (1) and (2) and 15.6 µg/mL for complex (3). Complexes (1) and (2) proved to be more active than complex (3) against the tested bacterial strains, both in planktonic and biofilm growth state, with MIC and minimal biofilm eradication concentration (MBEC) values ranging from 15.6 to 62.5 µg/mL, the best antibacterial effects being noticed against Staphylococcus aureus and Pseudomonas aeruginosa. Remarkably, the MBEC values obtained for the four tested bacterial strains were either identical or even lower than the MIC ones. The cytotoxicity assay indicated that the tested complexes affected the cellular cycle of HeLa, HCT-8, and MG63 cells, probably by inhibiting the expression of vimentin and transient receptor potential canonical 1 (TRPC1). The obtained biological results recommend these complexes as potential candidates for the development of novel anti-biofilm agents.

Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis, Characterization, DNA/Protein Binding and Cytotoxicity Studies.

"Drug repositioning" is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y3+, La3+, Sm3+, Eu3+, Gd3+, Tb3+) have been synthesized and characterized. The experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms; these findings are supported by DFT (density functional theory) calculations for the Sm3+ complex. The cytotoxic activity of the complexes, as well as the ligand, has been studied on MDA-MB 231 (human breast adenocarcinoma), LoVo (human colon adenocarcinoma) and HUVEC (normal human umbilical vein endothelial cells) cell lines. UV-Vis spectroscopy and competitive binding studies show that the complexes display binding affinities (Kb) towards double stranded DNA in the range of 9.33 × 104 - 10.72 × 105. Major and minor groove-binding most likely play a significant role in the interactions of the complexes with DNA. Moreover, the complexes bind human serum albumin more avidly than apo-transferrin.

Anti-biofilm Fe3O4@C18-[1,3,4]thiadiazolo[3,2-a]pyrimidin-4-ium-2-thiolate Derivative Core-shell Nanocoatings.

The derivatives 5,7-dimethyl[1,3,4]thiadiazolo[3,2-a]pyrimidin-4-ium-2-thiolate (1) and 7-methyl-5-phenyl[1,3,4]thiadiazolo[3,2-a]pyrimidin-4-ium-2-thiolate (2) were fully characterized by single-crystal X-ray diffraction. Their supramolecular structure is built through both π-π stacking and C=S-π interactions for both compounds. The embedment of the tested compounds into Fe3O4@C18 core-shell nanocoatings increased the protection degree against Candida albicans biofilms on the catheter surface, suggesting that these bioactive nanocoatings could be further developed as non-cytotoxic strategies for fighting biofilm-associated fungal infections.

Copper(II) Complexes with Mixed Heterocycle Ligands as Promising Antibacterial and Antitumor Species.

Complexes with mixed ligands [Cu(N-N)2(pmtp)](ClO4)2 ((1) N-N: 2,2'-bipyridine; (2) L: 1,10-phenanthroline and pmpt: 5-phenyl-7-methyl-1,2,4-triazolo[1,5-a]pyrimidine) were synthesized and structurally and biologically characterized. Compound (1) crystallizes into space group Pa and (2) in P-1. Both complexes display an intermediate stereochemistry between the two five-coordinated ones. The biological tests indicated that the two compounds exhibited superoxide scavenging capacity, intercalative DNA properties, and metallonuclease activity. Tests on various cell systems indicated that the two complexes neither interfere with the proliferation of Saccharomyces cerevisiae or BJ healthy skin cells, nor cause hemolysis in the active concentration range. Nevertheless, the compounds showed antibacterial potential, with complex (2) being significantly more active than complex (1) against all tested bacterial strains, both in planktonic and biofilm growth state. Both complexes exhibited a very good activity against B16 melanoma cells, with a higher specificity being displayed by compound (1). Taken together, the results indicate that complexes (1) and (2) have specific biological relevance, with potential for the development of antitumor or antimicrobial drugs.

X-ray Crystal Structure, Geometric Isomerism, and Antimicrobial Activity of New Copper(II) Carboxylate Complexes with Imidazole Derivatives.

Five new copper(II) acrylate complexes (acr is the acrylate anion: C3H3O2) with imidazole derivatives (2-methylimidazole/2-MeIm, 5-methylimidazole/5-MeIm, 2-ethylimidazole/2-EtIm) of type: cis-[Cu(2-RIm)2(acr)2]·xH2O ((1): R = ⁻CH3, x = 2; (4): R = ⁻CH2⁻CH3, x = 0), trans-[Cu(2-RIm)2(acr)2] ((2): R = ⁻CH3; (5): R = ⁻CH2⁻CH3) and trans-[Cu(5-RIm)2(acr)2] ((3): R = ⁻CH3) have been prepared and characterized by elemental analysis, Fourier Transform Infrared spectrometry (FTIR), Electron Paramagnetic Resonance (EPR), electronic reflectance spectroscopy, scanning electron microscopy, and mass spectrometry. The single crystal X-ray diffraction study of complexes (2) and (5) reveals that the copper(II) ion is located on an inversion center and show elongated octahedral geometry completed by two coplanar bidentate acrylates and two unidentate imidazole derivatives displayed in trans positions. For complex (4) the single crystal X-ray diffraction shows that the copper(II) ion is in a distorted octahedral environment which can be easily confused with a trigonal prism completed by two bidentate acrylates and two unidentate imidazole derivatives displayed in cis positions. These results indicate the fact that complexes (4) and (5) are the geometric isomers of the same compound bis(acrylate)-bis(2-ethylimidazole)-copper(II). Complexes (1) and (2), as well as (4) and (5), were produced simultaneously in the reaction of the corresponding copper(II) acrylate with imidazole derivatives in methanol solution. Furthermore, in order to be able to formulate potential applications of the obtained compounds, our next goal was to investigate the in vitro antimicrobial activity of the synthesized complexes against Gram-positive and Gram-negative bacteria, as well as fungal strains, of both clinical and ecological importance (biodeterioration of historical buildings). The trans isomers (2) and (5), followed by (4) have shown the broadest range of antimicrobial activity. In case of (1) and (2) isomers, the trans isomer (2) was significantly more active than cis (1), while the cis isomer (4) proved to be more active than trans (5). Taken together, the biological evaluation results indicate that the trans (2) was the most active complex, demonstrating its potential for the development of novel antimicrobial agents, with potential applications in the biomedical and restoration of architectural monuments fields.

Synthesis, Structural Characterization, Antimicrobial Activity, and In Vitro Biocompatibility of New Unsaturated Carboxylate Complexes with 2,2'-Bipyridine.

The synthesis, structural characterization, cytotoxicity, and antimicrobial properties of four new complexes formed by employing acrylate anion and 2,2'-bipyridine are reported herein. X-ray crystallography revealed the trinuclear nature of [Mn3(2,2'-bipy)2(C3H3O2)6] (1), meanwhile complexes with general formula [M(2,2'-bipy)(C3H3O2)2(H2O)x]∙yH2O ((2) M: Ni, x = 1, y = 0; (3) M: Cu, x = 1, y = 0; (4) M: Zn, x = 0, y = 1; 2,2'-bipy: 2,2'-bipyridine; C3H3O2: acrylate anion) were shown to be mononuclear. The lowest minimum inhibitory concentration (MIC) of 128 µg mL-1 was recorded for all four tested complexes against Candida albicans, for complex (3) against Escherichia coli, and for complex (4) against Staphylocococcus aureus. Compounds (3) and (4) were also potent efflux pumps activity inhibitors (EPI), proving their potential for use in synergistic combinations with antibiotics. Complexes (1)-(4) revealed that they were not cytotoxic to HCT-8 cells. They also proved to interfere with the cellular cycle of tumour HCT-8 cells by increasing the number of cells found in the S and G2/M phases. Taken together, these results demonstrate the potential of zinc and copper complexes for use in the development of novel antimicrobial and anti-proliferative agents.