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.

Do Young Consumers Care about Antioxidant Benefits and Resveratrol and Caffeic Acid Consumption?

Resveratrol and caffeic acid are some of the most consumed antioxidants during the day, so their importance as sources and their benefits need to be evaluated and updated. This survey aimed not only to analyze whether young Romanian consumers are informed about the benefits of antioxidants in general, and resveratrol and caffeic acid in particular, but also to observe the degree of nutritional education of these participants. Young consumers know the concept of antioxidants relatively well; they managed to give examples of antioxidants and indicate their effects. The majority of those chosen drink wine and coffee, but many are unaware of their health advantages and antioxidant properties. Students are less familiar with the antioxidant chemicals resveratrol and caffeic acid. It is advised to have a thorough understanding of these significant antioxidants and their nutritional content as they are present in our regular diets, and further studies on different kinds of antioxidants are required to increase the awareness of people concerning their importance in daily life.

In Vivo Biocompatibility Study on Functional Nanostructures Containing Bioactive Glass and Plant Extracts for Implantology.

In this paper, the in vivo behavior of orthopedic implants covered with thin films obtained by matrix-assisted pulsed laser evaporation and containing bioactive glass, a polymer, and natural plant extract was evaluated. In vivo testing was performed by carrying out a study on guinea pigs who had coated metallic screws inserted in them and also controls, following the regulations of European laws regarding the use of animals in scientific studies. After 26 weeks from implantation, the guinea pigs were subjected to X-ray analyses to observe the evolution of osteointegration over time; the guinea pigs' blood was collected for the detection of enzymatic activity and to measure values for urea, creatinine, blood glucose, alkaline phosphatase, pancreatic amylase, total protein, and glutamate pyruvate transaminase to see the extent to which the body was affected by the introduction of the implant. Moreover, a histopathological assessment of the following vital organs was carried out: heart, brain, liver, and spleen. We also assessed implanted bone with adjacent tissue. Our studies did not find significant variations in biochemical and histological results compared to the control group or significant adverse effects caused by the implant coating in terms of tissue compatibility, inflammatory reactions, and systemic effects.

In Vitro Characterization of Hydroxyapatite-Based Coatings Doped with Mg or Zn Electrochemically Deposited on Nanostructured Titanium.

Biomaterials are an important and integrated part of modern medicine, and their development and improvement are essential. The fundamental requirement of a biomaterial is found to be in its interaction with the surrounding environment, with which it must coexist. The aim of this study was to assess the biological characteristics of hydroxyapatite (HAp)-based coatings doped with Mg and Zn ions obtained by the pulsed galvanostatic electrochemical method on the surface of pure titanium (cp-Ti) functionalized with titanium dioxide nanotubes (NTs TiO2) obtained by anodic oxidation. The obtained results highlighted that the addition of Zn or Mg into the HAp structure enhances the in vitro response of the cp-Ti surface functionalized with NT TiO2. The contact angle and surface free energy showed that all the developed surfaces have a hydrophilic character in comparison with the cp-Ti surface. The HAp-based coatings doped with Zn registered superior values than the ones with Mg, in terms of biomineralization, electrochemical behavior, and cell interaction. Overall, it can be said that the addition of Mg or Zn can enhance the in vitro behavior of the HAp-based coatings in accordance with clinical requirements. Antibacterial tests showed that the proposed HAp-Mg coatings had no efficiency against Escherichia coli, while the HAp-Zn coatings registered the highest antibacterial efficiency.

Aptamer-Based Targeting of Cancer: A Powerful Tool for Diagnostic and Therapeutic Aims.

Cancer is known as one of the most significant causes of death worldwide, and, in spite of novel therapeutic methods, continues to cause a considerable number of deaths. Targeted molecular diagnosis and therapy using aptamers with high affinity have become popular techniques for pathological angiogenesis and cancer therapy scientists. In this paper, several aptamer-based diagnostic and therapeutic techniques such as aptamer-nanomaterial conjugation, aptamer-drug conjugation (physically or covalently), and biosensors, which have been successfully designed for biomarkers, were critically reviewed. The results demonstrated that aptamers can potentially be incorporated with targeted delivery systems and biosensors for the detection of biomarkers expressed by cancer cells. Aptamer-based therapeutic and diagnostic methods, representing the main field of medical sciences, possess high potential for use in cancer therapy, pathological angiogenesis, and improvement of community health. The clinical use of aptamers is limited due to target impurities, inaccuracy in the systematic evolution of ligands via exponential enrichment (SELEX)stage process, and in vitro synthesis, making them unreliable and leading to lower selectivity for in vivo targets. Moreover, size, behavior, probable toxicity, low distribution, and the unpredictable behavior of nanomaterials in in vivo media make their usage in clinical assays critical. This review is helpful for the implementation of aptamer-based therapies which are effective and applicable for clinical use and the design of future studies.

Development of biosensors for detection of fibrinogen: a review.

Fibrinogen as a major inflammation marker and blood coagulation factor has a direct impact on the health of humanity. The variations in fibrinogen content lead to risky conditions such as bleeding and cardiovascular diseases. So, accurate methods for monitoring of this glycoprotein are of high importance. The conventional methods, such as the Clauss method, are time consuming and require highly specialized expert analysts. The development of fast, simple, easy to use, and inexpensive methods is highly desired. In this way, biosensors have gained outstanding attention since they offer means for performing analyses at the points-of-care using self-testing devices, which can be applied outside of clinical laboratories or hospital. This review indicates that different electrochemical and optical sensors have been successfully implemented for the detection of fibrinogen under normal levels of fibrinogen in plasma. The biosensors for the detection of fibrinogen have been designed based on the quartz crystal microbalance, field-effect transistor, electrochemical impedance spectroscopy, amperometry, surface plasmon resonance, localized surface plasmon resonance, and colorimetric techniques. Also, this review demonstrates the utility of the application of nanoparticles in different detection techniques.

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%.

Synthesis and Investigation of Antibacterial Activity of Thin Films Based on TiO2-Ag and SiO2-Ag with Potential Applications in Medical Environment.

Multiple antibiotic resistance has now become a major obstacle to the treatment of infectious diseases. In this context, the application of nanotechnology in medicine is a promising alternative for the prevention of infections with multidrug-resistant germs. The use of silver as a powerful antibacterial agent has attracted much interest. TiO2 and SiO2 thin films enhanced with Ag particles have been developed with the aim of maintaining the transparency of the polymer films. Antibacterial activity was evaluated for a Gram-negative species-Escherichia coli-in concentrations of 105 and 104 CFU/mL in different conditions-activation by UV irradiation, single layer and double layer. Increased antibacterial efficacy of TiO2-deposited foil was found for the tests that had been exposed to UV activation. In the case of bilayer tests, the efficiency was higher compared to those in a single layer, as the contact surface between the films and the bacterial suspension increased. Films can be used as a potential method to limit bacterial growth on hospital surfaces, such as telephone screens and medical equipment, given their optimized characteristics and proven antibacterial efficacy.

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.

Aptamer-Based Lateral Flow Assays: Current Trends in Clinical Diagnostic Rapid Tests.

The lateral flow assay (LFA) is an extensively used paper-based platform for the rapid and on-site detection of different analytes. The method is user-friendly with no need for sophisticated operation and only includes adding sample. Generally, antibodies are employed as the biorecognition elements in the LFA. However, antibodies possess several disadvantages including poor stability, high batch-to-batch variation, long development time, high price and need for ethical approval and cold chain. Because of these limitations, aptamers screened by an in vitro process can be a good alternative to antibodies as biorecognition molecules in the LFA. In recent years, aptamer-based LFAs have been investigated for the detection of different analytes in point-of-care diagnostics. In this review, we summarize the applications of aptamer technology in LFAs in clinical diagnostic rapid tests for the detection of biomarkers, microbial analytes, hormones and antibiotics. Performance, advantages and drawbacks of the developed assays are also discussed.

DNA-templated electrodeposition of silver nanoparticles for direct and label-free aptasensing of ochratoxin A.

We present in this work, an aptasensing strategy based on the DNA-templated electrodeposition of silver nanoparticles (AgNPs). The homogeneous electro-deposition of AgNPs on screen printed carbon electrode (SPCE) surface was achieved based on a unique aptamer scaffold. This was constructed by immobilizing a DNA aptamer on SPCE by electrochemical oxidation of its amine groups. The electrodeposition of AgNPs was investigated before and after the addition of the aptamer's specific target; the mycotoxin, ochratoxin A (OTA). Electrochemical characterization by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) showed the effect of the scaffold layer on the electrodeposition of AgNPs. The conformational change induced by aptamer after binding its targeted molecule affects AgNPs electrodeposition and the electron transfer thus allowing OTA detection by cyclic voltammetry. The voltammograms showed a good proportionality between the analyte concentration and the current response. The constructed platform allowed the quantitative aptasensing of OTA within the range of (1.56-400 ng/mL) and the detection limit of 0.6 ng/mL. In term of aptasensor applicability, the proposed strategy showed excellent performance in rice samples.

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.