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Four solution-stable copper(ii) complexes of pyridine and pyridine-based alcohols were investigated by spectroscopic and thermal methods; the magnetic and anticancer properties were discussed as well.

We present the synthesis, physicochemical and biological activity of new Ru(ii) and Ir(iii) complexes ((Ru(η6-p-cymene)Cl2PPh2CH2OH, Ru(η6-p-cymene)Cl2P(p-OCH3Ph)2CH2OH), (Ir(η5-Cp*)Cl2P(p-OCH3Ph)2CH2OH, Ir(η5-Cp*)Cl2PPh2CH2OH).

Novel heteronuclear IrIII–CuII coordination compounds ([Ir(η5-Cp*)Cl2Pcfx-Cu(phen)](NO3)·1.75(CH3OH)·0.75(H2O) (1), [Ir(η5-Cp*)Cl2Pnfx-Cu(phen)](NO3)·1.75(CH3OH)·0.75(H2O) (2), [Ir(η5-Cp*)Cl2Plfx-Cu(phen)](NO3)·1.3(H2O)·1.95(CH3OH) (3), [Ir(η5-Cp*)Cl2Psfx-Cu(phen)] (4)) bearing phosphines derived from fluoroquinolones, namely, sparfloxacin (Hsfx), ciprofloxacin (Hcfx), lomefloxacin (Hlfx), and norfloxacin (Hnfx), have been synthesized and studied as possible anticancer chemotherapeutics. All compounds have been characterized by electrospray ionization mass spectrometry (ESI-MS), a number of spectroscopic methods (i.e., IR, fluorescence, and electron paramagnetic resonance (EPR)), cyclic voltammetry, variable-temperature magnetic susceptibility measurements, and X-ray diffractometry. The coordination geometry of IrIII in all complexes adopts a characteristic piano-stool geometry with the η5-coordinated and three additional sites occupied by two chloride and phosphine ligands, while CuII ions in complexes 1 and 2 form a distorted square-pyramidal coordination geometry, and in complex 3, the coordination geometry around CuII ions is a distorted octahedron. Interestingly, the crystal structure of [Ir(η5-Cp*)Cl2Plfx-Cu(phen)] features the one-dimensional (1D) metal–organic polymer. Liposomes loaded with redox-active and fluorescent [Ir(η5-Cp*)Cl2Pcfx-Cu(phen)] (1L) have been prepared to increase water solubility and minimize serious systemic side effects. It has been proven, by confocal microscopy and an inductively coupled plasma mass spectrometry (ICP-MS) analysis, that the liposomal form of compound 1 can be effectively accumulated inside human lung adenocarcinoma and human prostate carcinoma cells with selective localization in nuclei. A cytometric analysis showed dominance of apoptosis over the other cell death types. Furthermore, the investigated nanoformulations induced changes in the cell cycle, leading to S phase arrest in a dose-dependent manner. Importantly, in vitro anticancer action on three-dimensional (3D) multicellular tumor spheroids has been demonstrated., This research was funded by the Polish National Science Centre (grant number 2020/37/N/ST4/02698). NANBIOSIS ICTS and ELECMI-LMA ICTS are gratefully acknowledged.

This work describes the traditional wet and green synthetic approaches, structural features, and extensive bioactivity study for a new coordination polymer [Ag(

The aim of this work was the evaluation of biological properties of hybrid coatings modified with Ag, Cu, and Zn nanoparticles (NPs) applied on TPLO medical implants by the sol-gel process. The implant coatings enriched with various concentrations of metallic NPs were investigated in the in vitro bactericidal efficacy tests against Gram+ and Gram- bacteria and pathogenic yeast. Next, the designed materials were tested on human osteosarcoma cell lines. The cells adhesion, proliferation, viability, and differentiation were investigated. The cell growth wasevaluated using SEM, and the metallic ion release was measured. The results revealed that the NPs concentration in the hybrid layers decreased with the incubation time. In the last stage, the implants were tested in vivo on six canine patients. Three months after the operation, the radiological evaluation of the performed anastomosis was carried out as well as the histopathological evaluation of tissue regeneration. The strongest bactericidal efficacy was observed for the layers containing AgNPs. Along with an increased concentration of metallic additives, a growing toxic effect was clearly observed. The most pronounced toxic effect was especially evident with the AgNPs concentration exceeding 1 mol %. In all the operated patients, no deviations were found during the follow-up examinations in the postoperative period. The low dose of AgNPs in the hybrid layer facilitated the tissue healing process. It was proven that silver nanoparticles may accelerate the bone healing process. The correct tissue reparation was observed.

The ability of the studied FomA protein fragments of Fusobacterium nucleatum (Fn) with copper(ii) ions (Cu(ii)-Ac-KGHGNGEEGTPTVHNE-NH2 (1Cu) and its cyclic analogue Cu(ii)-cyclo(KGHGNGEEGTPTVHNE) (2Cu)) to induce reactive oxygen species (ROS) generation, as a result of red-ox processes, was determined by UV-Vis, luminescence methods, spin trapping and cyclic voltamperometry. The contribution of 1O2 and ˙OH to DNA degradation was proved using gel electrophoresis. Furthermore, the pronounced generation of ROS by mouse colon carcinoma cells (CT26) stimulated by both copper(ii) complexes was confirmed. A fluorescence method allowed the total amounts of ROS generated inside the CT26 cells to be detected, while the spin trapping technique proved that free radicals mainly attached to the membrane surface. These last results are in agreement with the data obtained from the ICP-MS method, which demonstrates that 1Cu and 2Cu complexes are not efficiently accumulated inside the cell. Furthermore, the role of ROS in lipid peroxidation was established. The above-mentioned factors may clearly indicate the contribution of ROS generated by the studied copper(ii) complexes to colonic cell damage, which can lead to a carcinogenesis process. This study may be an important step to recognize and understand the mechanism of colon cancer initiation.

Implant-associated infections are the major concern for failure of arthroplasty operations. The functionalisation of implant surface can provide solutions to the problem by either inhibiting the adherence of the bacteria or introducing a contact-killing mechanism. This work is focused on Ti6Al7Nb biomedical alloy modification involving chemical and plasma surface activation, followed by the deposition of chitosan layers enhanced with metal nanoparticles. A benign method using chitosan as an efficient reducing and stabilizing agent was applied to produce Au and Ag nanoparticles in situ with the size of ca. 20 nm and 5 nm, respectively. Piranha solution and O2/NH3/Ar plasma were used as a surface activation method, while Au and Ag NPs provide antimicrobial properties, as a viable alternative to the antibiotic-based approach. The surface topography on submicrometre scale of deposited layers was evaluated. Chitosan and chitosan–Ag NPs composite layers showed excellent hydrophilicity, characterised by wetting angles below 13°. Modified alloy showed minimal toxicity towards MG-63 cell line in vitro, acceptable corrosion resistance and release of titanium, aluminium as well as niobium ions from the resulting modified alloys. The chitosan layers were proven to uphold satisfactory Au (over 2.8 mg/dm3) and Ag (over 5.1 mg/dm3) ion dosages up to 96h.

Tailoring surface properties by layer-by-layer (LBL) deposition directed on the construction of complex multilayer coatings with nanoscale precision enables the development of novel structures and devices with desired functional properties (i.e., osseointegration, bactericidal activity, biocorrosion protection). Herein, electrostatic self-assembly was applied to fabricate biopolymer-based coatings involving chitosan (CSM) and alginate (AL) enriched with caffeic acid (CA) on Ti-6Al-7Nb alloyed surfaces. The method of CA grafting onto the chitosan backbone (CA-g-CSM) as well as all used reagents for implant functionalization were chosen as green and sustainable approach. The final procedure of surface modification of the Ti-6Al-7Nb alloy consists of three steps: (i) chemical treatment in Piranha solution, (ii) plasma chemical-activation of the Ti alloy surface in a RF CVD (Radio Frequency Chemical Vapour Deposition) reactor using Ar, O2 and NH3 gaseous precursors, and (iii) a multi-step deposition of bio-functional coatings via dip-coating method. Corrosion tests have revealed that the resulting chitosan-based coatings, also these involving CA, block the specimen surface and hinder corrosion of titanium alloy. Furthermore, the antioxidant layers are characterized by beneficial level of roughness (Ra up ca. 350 nm) and moderate hydrophilicity (59°) with the dispersion part of conducive surface energy ca. 30 mJ/m2. Noteworthy, all coatings are biocompatible as the intact morphology of cultured eukaryotic cells ensured proper growth and proliferation, while exhibit bacteriostatic character, particularly in contact with Gram-(−) bacteria (E. coli). The study indicates that the applied simple sustainable strategy has contributed significantly to obtaining homogeneous, stable, and biocompatible while antibacterial biopolymer-based coatings., This work has been supported by the National Science Centre (NCN) (grant decision no. DEC-2017/01/X/ST8/00886).

After plasmochemical activation, chitosan-based coatings (containing silver or gold nanoparticles) were applied on nitinol (NiTi) alloy surface to study the effect of this functionalization on i) wettability, ii) corrosion resistance, iii) release of metal ions, and iv) cytotoxicity. Surface modification of nitinol based on (1) Ar/O2/NH3 plasma treatment and deposition of chitosan/AgNPs/vit.C coating (CS/AgNPs) or (2) Ar/O2/NH3 plasma treatment and deposition of chitosan/AuNPs coating (CS/AuNPs) resulted in decrease in water contact angle (enhanced hydrophilicity), increase in surface roughness parameters, improvement of corrosion resistance, and good biocompatibility (proved on human osteoblast-like cells in vitro), when compared to both unmodified NiTi and the chitosan layer itself. The proposed surface functionalization can potentially be a powerful and promising strategy for reducing pathogenic microorganism-associated infections without harmful effects towards mammalian cells, thus facilitating proper osseointegration.

Novel half-sandwich iridium(III) complexes with aminomethyl(diphenyl)phosphine derived from fluoroloquinolones (IrPCp, IrPSf, IrPLm, IrPNr) were studied as possible anticancer chemotherapeutics and showed higher potency than other well-known metal-based agents i.e., Pt(II) drugs. All compounds were characterized by elemental analysis, selected spectroscopic methods (i.e., absorption and fluorescence spectroscopy, NMR), ESI-MS spectrometry, X-ray diffraction, and electrochemical techniques. The studied complexes exhibited promising cytotoxicity in vitro with IC50 values significantly lower than that of the reference drug – cisplatin. The insight into the mode of action revealed the uniform distribution of the Ir(III) complexes in both the nucleus and cytoplasm (Pearson's co-localization coefficient of 0.63). Precise cytometric analysis provided clear evidence for the predominance of apoptosis in the induced cell death. The activation of caspase-3/7 along with the decrease of mitochondrial membrane potential also confirmed the apoptotic cell death. The investigated Ir(III) complexes may induce changes in the cell cycle leading to G2/M phase arrest. ROS generation as a plausible pathway responsible for the cytotoxicity was confirmed by determination of redox potentials enabling efficient ROS production. Furthermore, Pluronic P-123 micelles loaded with selected Ir(III) complexes were proposed to overcome low solubility and to minimize serious systemic side effects by administering the complex in a controlled manner. The resulting nanoformulations (IrPCp_M, IrPNr_M) facilitated efficient drug accumulation for human lung adenocarcinoma and human prostate carcinoma (A549 and DU-145 cell lines), as demonstrated by confocal microscopy and ICP-MS analysis. In vitro cytotoxicity assays were also carried out within multicellular tumor spheroids and efficient anticancer action on these 3D assemblies was demonstrated., The UV-Vis and cyclic voltamperometry measurements were carried out with the equipment purchased thanks to the financial support of the Polish National Science Centre (Grant 2016/23/D/ST5/00269).

Novel half-sandwich ruthenium(II) complexes with aminomethyl(diphenyl)phosphine derived from fluoroloquinolones (RuPCp, RuPSf, RuPLm, RuPNr) were being investigated as alternatives to well-established metal-based chemotherapeutics. All compounds were characterized by elemental analysis, selected spectroscopic methods (i.e., absorption and fluorescence spectroscopies, ESI-MS, NMR, circular dichroizm), X-ray diffractometry, ICP-MS, and electrochemical techniques. To overcome low solubility, serious side effects connected with systemic cytotoxicity of ruthenium complexes, and acquiring the resistance of cancer cells, polymeric nanoformulations based on Pluronic P-123 micelles loaded with selected Ru(II) complexes were prepared and characterized. Resulting micelles (RuPCp_M, RuPNr_M) enabled efficient drug accumulation inside human lung adenocarcinoma (A549 tumor cell line), proved by confocal microscopy and ICP-MS analysis, allowing cytotoxic action. Studied complexes exhibited promising cytotoxicity in vitro with IC50 values significantly lower than the reference drug - cisplatin. The fluorescence spectroscopic data (CT-DNA titration, in vitro cell staining) together with analysis of DNA fragmentation (pBR322 plasmid, comet assay) provided clear evidence for the interaction with DNA inducing apoptotic cell death.

In this paper, we present a comparative study on the cytotoxic mode of action of copper(I) and copper(II) complexes with phosphine derivatives of fluoroquinolone antibiotics (ciprofloxacin HCp and norfloxacin HNr). The in vitro cytotoxic activity of four new compounds was tested against two selected cancer cell lines. All complexes exhibited much better cytotoxicity against both cell lines than unmodified fluoroquinolone antibiotics, their phosphines (PCp, PNr), chalcogenide derivatives (oxides: OPCp, OPNr; sulfides: SPCp, SPNr and selenides: SePCp, SePNr) and previously described by us complexes with phosphines derived from different fluoroquinolones: lomefloxacin (HLm) and sparfloxacin (HSf) as well as cisplatin. Apoptosis, observed at a great predominance, was induced by all studied complexes. Importantly, it was concluded that coordination compounds with Cu(I) ion ([CuI-PNr] and [CuI-PCp]) were much more active than those with Cu(II) ion ([OPNr-CuII], [OPCp-CuII]), even though the highest efficacy to produce reactive oxygen species, participating in overall cytotoxicity, was proved for copper(II) complexes among all studied compounds. Herein, we discuss not only results obtained for copper(I)/(II) complexes with phosphines derived from HNr and HCp but we also compare them to previously described data for complexes with HLm and HSf derivatives. This is the first insight into a structure-activity relationship of copper complexes with phosphine derivatives of fluoroquinolone antibiotics.

Reaction of {[Ru(η6-p-cymene)Cl]2(μ-Cl)2} (1) with aminomethylphosphane derived from morpholine (P{CH2N(CH2CH2)2O}3 (A), PPh2{CH2N(CH2CH2)2O} (B)) or piperazine (P{CH2N(CH2CH2)2NCH2CH3}3 (C), PPh2{CH2N(CH2CH2)2NCH2CH3} (D)) results in four new piano stool ruthenium(II) coordination compounds: [Ru(η6-p-cymene)Cl2(A)] (2A), [Ru(η6-p-cymene)Cl2(B)] (2B), [Ru(η6-p-cymene)Cl2(C)] (2C) and [Ru(η6-p-cymene)Cl2(D)] (2D). Every complex was fully characterized using spectroscopic methods (1H, 13C{1H}, 31P{1H} NMR and ESI-MS), elemental analysis, X-ray single crystal diffraction and DFT calculations. Preliminary studies of in vitro cytotoxicity on the A549 (human lung adenocarcinoma) and MCF7 (human breast adenocarcinoma) cell lines revealed 2A-2D activity in the same order of magnitude as in the case of cisplatin. Additionally, the study confirmed the ability of 2A-2D to interact with DNA helix and transferrin.

An explanation of carcinogenesis processes may certainly contribute to the prevention and development of novel methods for cancer treatment. In this paper, we considered the probable relationship between the presence of

Phosphonium salt (p-OCH

An explanation of carcinogenesis processes may certainly contribute to the prevention and development of novel methods for cancer treatment. In this paper, we considered the probable relationship between the presence of Fusobacterium nucleatum in the colon and its possible influence on the development of colorectal cancer. For this purpose, intracellular and/or extracellular generation of reactive oxygen species (ROS) by mouse colon carcinoma cells (CT26) was stimulated by two fragments of FomA adhesin from F. nucleatum and their complexes with copper(II): Cu(II)-Ac-KGHGNG-NH2 (1Cu) and Cu(II)-Ac-PTVHNE-NH2 (2Cu). Incubation of the cells with copper complexes was followed with ICP-MS technique. The overall generation of ROS was shown by means of fluorescence spectroscopy with two proper probes, whereas identification of ROS was achieved by the spin trapping technique and electron paramagnetic resonance measurements. As a result, an abundant production of the hydroxyl radicals, both inside and outside the cells, was observed upon the stimulation of the CT26 cells with the copper complexes. Clearly both compounds induced strong oxidation stress which triggered a radicals' cascade that finally resulted in the pronounced lipid peroxidation. The latter was evidenced with the measured level of malondialdehyde, a biomarker of the peroxidation process. By applying N-acetylcysteine antioxidant to the studied system, the free radical mechanism of the lipid peroxidation process was confirmed. Hypothetically this mechanism can lead to colon cell damage and further cancerogenesis processes.

The photogeneration of reactive oxygen species (ROS) by molecular and nanostructured systems with d- and f-metal compounds is discussed with the emphasis on the mechanisms involved in the process. The effectiveness of ROS photogeneration in various systems from simple metal complexes with non-macrocyclic and macrocyclic ligands, through more complex supramolecular scaffolds, up to nano-platforms and hybrid materials is reviewed considering their biological and medical applications. A particular emphasis is focused on the comparison of mechanisms of ROS photogeneration exploited in d- versus f-metal systems. Perspectives for each type of systems are also outlined.

Poly(lactic acid) (PLA) and its copolymers are widely used in biomedical applications due to their excellent biocompatibility and tunable physicochemical properties. Various delivery systems, such as depot, micelle, implant, injectable suspension, and particles have been explored with these copolymers ranging from nano to micron size. The clinical translation of these systems from preclinical experimental settings is an ever-evolving field with incremental advancements. PLA and its copolymer based particulate system are well-known for controlled delivery of various therapeutic molecules, including drugs, proteins, genes, and vaccines. They have marked their presence in the market for the treatment of various diseases. Despite continuous innovations in particulate formulation technology, these particles face many challenges, such as low encapsulation efficiency, termination sterilization, particle heterogeneity, etc. This chapter describes formulation aspects of poly(lactic acid) and its copolymer based particulate system, ongoing research in this area, and clinical products available on market. Existing challenges associated with formulation and delivery are also covered.

The work presents a detailed study on the diamond-like structures doped with Si atoms and biopolymers-based coatings (chitosan, alginate) enriched with Ag nanoparticles (Ag NPs) deposited on the Ti-6Al-7Nb substrate. Multilayers were obtained by Plasma Enhanced Radio Frequency Chemical Vapour Deposition (PE RF CVD) technique and subsequent deposition of biopolymers by immersion method. The impact of Si atoms and Ag NPs on chemical structure, microstructure, topography, cytotoxicity as well as the hardness and Young modulus of the resulting layers was precisely investigated. The most advantageous conditions of plasma functionalization in RF reactor were the mixture of O2-Ar-NH3 in volume ratio of 10/1/9 in the first stage of functionalization (pre-activation). In the case of Si-DLC coatings (up to ca. 19 at.%) the lower silane flow (4 cm3/min) resulted in significant decrease of surface roughness (up to ca. Ra = 0.71 nm) of modified surfaces and increase of hardness reaching ca. 900 nm depth into surface (up to ca. 16 GPa). The most attractive among biopolymer-based coating on Ti-6Al-7Nb in terms of biological activity was chitosan with Ag NPs (diameter of ca. 25 nm) with additional alginate layer. AFM analysis revealed a uniform distribution of Ag NPs in the chitosan matrix. This contributed to advantageous physicochemical and biological properties assuring proper cell adhesion and proliferation. Noteworthy, the resulting surface functionalization of Ti-6Al-7Nb alloy did not cause significant cytotoxicity in vitro, giving a strong hope for perspective applications in implantology.

Gold(III) complex containing 2-pyridineethanol has been synthesized and characterized structurally by single crystal X-ray diffraction, vibrational spectroscopy, 1H NMR spectroscopy, electrochemical study, and DFT calculations. The Au(III) ion is four coordinated with one N–donor ligand (L) and three Cl anions. The Okuniewski's (τ’4=0.018) has been used to estimate the angular distortion from ideal square planar geometry. The vibrational spectroscopy studies, in the solid state and DMSO solution and cyclic voltammetry, have been performed to determine its stability and redox activity, respectively. A complete assignment of the IR and Raman spectra has been made based on the calculated potential energy distribution (PED). The theoretical calculations have been made for two functionals and several basis sets. The compound has been evaluated for its antiproliferative properties in a human lung adenocarcinoma cell line (A549), mouse colon carcinoma (CT26), human breast adenocarcinoma (MCF-7), human prostate carcinoma derived from the metastatic site in the brain (DU-145), and PANC-1 human pancreas/duct carcinoma cell line and non-tumorigenic cell lines: HaCat (human keratinocyte), and HEK293T (human embryonic kidney). Au(III) complex cytotoxicity is significantly against A549 and MCF-7 cells as in the reference drug: cisplatin. Studies of the interactions of Au(III) complex with DNA, HSA (human serum albumin) have been performed. The results from modeling docking simulations indicate that the title complex exerts anticancer effects in vitro based on different mechanisms of action to compare with cisplatin.

An eco-friendly, efficient, and controlled synthesis of gold nanoparticles with application of the aqueous extract of Rosa damascena (Au@RD NPs) without using any other reducing agents was studied. Au@RD NPs of narrow size distribution were characterized by UV–vis and FT-IR spectroscopies, transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, particle size analysis, and zeta potential measurements. In vitro stability experiments revealed that the Au@RD NPs were stable for over a year (pH ~ 3.5), proving a significant stabilizing potential of the aqueous RD extract. The high total content of polyphenols, flavonoids, and reducing sugars along with the powerful antioxidant activity of the RD extract was determined by spectroscopic and analytical methods. Colloids prepared from the purified and lyophilized Au@RD NPs (electrokinetic potential of ca. -33 mV) were stable for at least 24 h under terms similar to physiological conditions (pH = 7.4, PBS). The in vitro cytotoxicity of Au@RD NPs was investigated against peripheral blood mononuclear lymphocytes (PBML), acute promyelocytic leukemia (HL60), and human lung adenocarcinoma (A549). Selective cytotoxicity of Au@RD NPs towards cancer cells (HL60, A549) over normal cells (PBML) in vitro was explicitly demonstrated by viability assays. Comet assay revealed a higher level of DNA damages in cancer cells when compared with normal ones. Apoptotic death in cancer cells was proved by measuring caspases activity. Thus, the developed Au@RD NPs, obtained by the plant-mediated green synthesis, are attractive hybrid materials for the medical applications combining two active components – metal nanoparticles platform and plant-derived metabolites., This work was partially funded by the Scientific Fund of Andrzej Frycz Modrzewski Krakow University, Poland grant number 26/2018.

The aim of the work was to develop innovative antibacterial hybrid coatings applied on implants that are used for anastomoses of animals' long bones and to assess their physicochemical and biological properties. Plates made of the titanium alloy were covered with composite hybrid layers so as to protect the implant surface against corrosion and to enhance it with antibacterial properties.The hybrid coatings were obtained electrochemical oxidation and sol-gel. First, a layer of titanium nanotubes was applied to the implants surface through anodization. Next, the sol-gel method was used to create the second layer with silver nanoparticles. The microstructure examination of the materials was performed with the SEM. The phase composition analysis was carried out via the X-ray diffraction. The surface parameters (roughness, contact angle and free surface energy) were assessed. Biological studies of implants were conducted, including the analysis of degradation processes, cell response and bactericidal activity. The results confirmed that the hybrid antibacterial layers effectively protected the implant surface against scratches and corrosion and eliminated bacteria, which in turn would promote bone healing. The advantageous physicochemical and biological properties of metallic implants with hybrid composite layers raise hopes for their applicability in the veterinary treatment of bone fractures.

Antimicrobial polymers (APs) are the new type of disinfectants, which can be used in some cases as an alternative to nowadays overused antibiotics. This review presents the most prognostic approaches in tackling infections and drug resistance with application of antimicrobial polymers. We describe membrane-active formulations composed of antimicrobial polymers with attention paid to drug delivery systems and selected methods of visualization of the antimicrobial effect. Importantly, antimicrobial polymers can not only be used independently but as well they can be tethered to surfaces without losing their biological activity. The latter approach enables the design of surfaces that (i) inactivate microbes even without releasing additional biocides or (ii) enhance antimicrobial activity of these biocides acting by additive or synergistic effect. One of the hallmarks of APs is their low susceptibility to the current and/or emerging resistance mechanisms. Simplicity of modulation of the antimicrobial activity by easy changes in their structures and the related optimization of biological potential make the formulations composed of antimicrobial polymers clinically relevant materials.

The copper(II) ion binding of the Ac-KGHGNG-NH2 and Ac-PTVHNE-NH2 fragments of FomA adhesin from Fusobacterium nucleatum was studied using potentiometry, UV-Vis, CD, EPR and DFT techniques. The coordination pattern was described in a wide range of pH values. Ligands begin interactions with metal ions using imidazole nitrogen. At pH 6.8 (a value typical of the large intestine environment), the metal ion was coordinated by the 3N donor atoms {Nim, 2 × N−amide} in both cases. However, the copper(II) ion was bound more effectively by the Ac-PTVHNE-NH2 peptide. The formation of reactive oxygen species (ROS) was studied by UV-Vis and fluorescence spectroscopy, as well as gel electrophoresis in the presence of H2O2 and/or ascorbic acid. The complexes generated ROS in the highest amounts among all compounds. Moreover, they stimulated the CT26 cell line (mouse colon carcinoma) to produce ROS which lead to oxidative stress. It was also determined that such radicals took part in the plasmid degradation mechanism.

Central venous access devices play an important role in patients with prolonged intravenous administration requirements. In the last years, the coating of these devices with bactericidal compounds has emerged as a potential tool to prevent bacterial colonization. Our study describes the modification of 3D-printed reservoirs and silicone-based catheters, mimicking central venous access devices, through different approaches including their coating with the well known biocompatible and bactericidal polymer chitosan, with the anionic polysaccharide alginate; also, plasma treated surfaces were included in the study to promote polymer adhesion. The evaluation of the antimicrobial action of those surface modifications compared to that exerted by a model antibiotic (ciprofloxacin) adsorbed on the surface of the devices was carried out. Surface characterization was developed by different methodologies and the bactericidal effects of the different coatings were assayed in an in vitro model of Staphylococcus aureus infection. Our results showed a significant reduction in the reservoir roughness (≤73%) after coating though no changes were observed for coated catheters which was also confirmed by scanning electron microscopy, pointing to the importance of the surface device topography for the successful attachment of the coating and for the subsequent development of bactericidal effects. Furthermore, the single presence of chitosan on the reservoirs was enough to fully inhibit bacterial growth exerting the same efficiency as that showed by the model antibiotic. Importantly, chitosan coating showed low cytotoxicity against human keratinocytes, human lung adenocarcinoma epithelial cells, and murine colon carcinoma cells displaying viability percentages in the range of the control samples (>95%). Chitosan-based coatings are proposed as an effective and promising solution in the prevention of microbial infections associated to medical devices.

In this paper, the surface properties and selected mechanical and biological properties of various multi-layer systems based on diamond-like carbon structure deposited on low-density polyethylene (LDPE) substrate were studied. Plasma etching and layers deposition (incl. DLC, N-DLC, Si-DLC) were carried out using the RF CVD (radio frequency chemical vapor deposition) method. In particular, polyethylene with deposited N-DLC and DLC layers in one process was characterized by a surface hardness ca. seven times (up to ca. 2.3 GPa) higher than the unmodified substrate. Additionally, its surface roughness was determined to be almost two times higher than the respective plasma-untreated polymer. It is noteworthy that plasma-modified LDPE showed no significant cytotoxicity in vitro. Thus, based on the current research results, it is concluded that a multilayer system (based on DLC coatings) obtained using plasma treatment of the LDPE surface can be proposed as a prospective solution for improving mechanical properties while maintaining biocompatibility.

The main disadvantage of conventional anticancer chemotherapy is the inability to deliver the correct amount of drug directly to cancer. Those molecular delivering systems are very important to destroy cancer cells selectively. Herein we report synthesis of phosphine-peptide conjugate (Ph2PCH2-Sar-Gly-OH, PSG) derived from SarGly (sarcosine-glycine), which can be easily exchanged to other peptide carriers, its oxide (OPh2PCH2-Sar-Gly-OH, OPSG) and the first copper(I) complex ([CuI(dmp)(P(Ph)2CH2-Sar-Gly-OH)], 1-PSG, where dmp stands for 2,9-dimethyl-1,10-phenanthroline). The compounds were characterized by elemental analysis, NMR (1D, 2D), UV-Vis spectroscopy and DFT (Density Functional Theory) methods. PSG and 1-PSG proved to be stable in biological medium in the presence of atmospheric oxygen for several days. The cytotoxicity of the compounds and cisplatin was tested against cancer cell lines: mouse colon carcinoma (CT26; 1-PSGIC50 = 3.12 ± 0.1), human lung adenocarcinoma (A549; 1-PSGIC50 = 2.01 ± 0.2) and human breast adenocarcinoma (MCF7; 1-PSGIC50 = 0.98 ± 0.2) as well as against primary line of human pulmonary fibroblasts (MRC-5; 1-PSGIC50 = 78.56 ± 1.1). Therapeutic index for 1-PSG (MCF7) equals 80. Intracellular accumulation of 1-PSG complex increased with time and was much higher (96%) inside MCF7 cancer cells than in normal MRC5 cells (20%). Attachment of SarGly to cytotoxic copper(I) complex via phosphine motif improved selectivity of copper(I) complex 1-PSG into the cancer cells. Precise mechanistic study revealed that the 1-PSG complex causes apoptotic cells MCF7 death with simultaneous decrease of mitochondrial membrane potential and increase of caspase-9 and -3 activities. Additionally, 1-PSG generated high level of reactive oxygen species that was the reason for oxidative damages to the sugar-phosphate backbone of plasmid DNA.

The cytotoxic effect of iodide or thiocyanate copper(i) complexes (1-PSf, 2-PSf, 3-PSf, 4-PSf) with phosphine derived from sparfloxacin (HSf) and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as diimine auxiliary ligands was proved in vitro on somatic (MRC-5) and neoplastic (MCF7) human cell lines. Differences in mode of action were investigated in-depth for the selected dmp and bq complexes (1-PSf, 3-PSf, respectively) by elucidation of the following: (i) the efficiency to produce reactive oxygen species (ROS) in biological systems (cyclic voltammetry); (ii) their impact on mitochondrial membrane potential; (iii) potency for the activation of caspases 3 and 9; (iv) influence on the degree of DNA degradation (comet assay). It was concluded that the apoptosis of cancer cells is directly connected to the caspase-dependent mitochondrial pathway and supported by ROS production along with irreversible DNA fragmentation. Finally, it was demonstrated that the selected copper(i) complex encapsulated inside liposomes (1-PSf-L) exhibited enhanced accumulation inside cancer cells. This resulted in its higher cytotoxicity against cancer cells with therapeutic index of ca. 60. Increased selective accumulation in active neoplasm with simultaneous enhanced bioavailability and reduced systemic toxicity of liposomal formulation of copper(i) complexes can result in the development of new copper-based therapeutics and their successful implementation in anticancer chemotherapy.

Engineered biomaterials have revolutionized current medicine significantly, expanding the range of tools offered even for theragnosis. Such innovative systems find various practical applications in cancer therapy and diagnosis, bacterial infections treatment, acceleration of wound healing, etc. Basic surface chemistry methods coupled with advanced physiochemical modification produce innovative hybrid coatings for both metallic and polymeric substrates. In particular, plasma-assisted chemical grafting methods enable surface functionalization of biomaterials providing covalent bonds between the substrate and the polymer monomers. These thermodynamically stable layers with high energy bonds offer the possibility to obtain advanced hybrid systems for various medical applications, including drug delivery systems. The current state of the engineered systems based on plasma-induced grafting biopolymers and promising new research directions for orthopedics, implantology, tissue engineering, wound regeneration and infections control, as well as production of medical devices will be identified and reviewed.

We synthesized two derivatives of sparfloxacin (HSf): aminomethyl(diphenyl)phosphine (PSf) and its oxide (OPSf). The compounds were characterized by NMR spectroscopy, MS and elemental analysis. In addition, the molecular structures of the compounds were determined using DFT and X-ray (OPSf) analysis. The antibacterial activity of HSf and both derivatives was tested against four reference and fifteen clinical Gram-positive and Gram-negative strains of bacteria (sensitive or resistant to fluoroquinolones). The results showed that the activity of PSf was similar to or higher than the activity of HSf, while OPSf was found significantly less active. The compounds were also tested in vitro toward the following cancer cell lines: mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). Regardless of the cancer cell line, derivatization of HSf resulted in the gradual increase of cytotoxicity. OPSf exhibited the highest one (4 h – incubation time: IC50(CT26) = 51.0 ± 1.2; IC50(A549) = 74.9 ± 1.4 and 24 h: IC50(CT26) = 109.2 ± 8.8; IC50(A549) = 52.7 ± 9.2).

In this paper we report the reaction of [Ru(η5-C5H5)Cl(PPh3)2] with P{CH2N(CH2CH2)2O}3 in the presence of NaBF4, in which, apart from the Cl− substitution, an unexpected P–C bond cleavage in the tertiary phosphane is observed. It results in the formation of [Ru(η5-C5H5)(PH{CH2N(CH2CH2)2O}2)(PPh3)2]BF4 (1) – the first “piano-stool” ruthenium complex with a secondary aminomethylphosphane ligand.

In this paper, we present a comparative study on the cytotoxic mode of action of copper(I) and copper(II) complexes with phosphine derivatives of fluoroquinolone antibiotics (ciprofloxacin HCp and norfloxacin HNr). The in vitro cytotoxic activity of four new compounds was tested against two selected cancer cell lines. All complexes exhibited much better cytotoxicity against both cell lines than unmodified fluoroquinolone antibiotics, their phosphines (PCp, PNr), chalcogenide derivatives (oxides: OPCp, OPNr; sulfides: SPCp, SPNr and selenides: SePCp, SePNr) and previously described by us complexes with phosphines derived from different fluoroquinolones: lomefloxacin (HLm) and sparfloxacin (HSf) as well as cisplatin. Apoptosis, observed at a great predominance, was induced by all studied complexes. Importantly, it was concluded that coordination compounds with Cu(I) ion ([Cu

Goserelin acetate (Gos) as a synthetic analog of the mammalian gonadotropin-releasing hormone (GnRH) is widely used in the treatment of sex hormone-related conditions. In this paper we present the chemical and biological aspects of its interaction with Cu(II) ions. The mode of Cu(II) binding and the thermodynamic stability of the obtained complexes were characterized by potentiometry, UV-Vis and CD spectroscopic methods. The DFT calculations were applied in order to investigate and confirm the molecular structure of the studied systems. The experimental and theoretical results clearly indicated the involvement of three nitrogens from the peptide and two oxygens from the acetate moieties in the Cu(II) coordination under physiological conditions. The investigated metallopeptide caused single- and/or double cleavage of the sugar-phosphate backbone of the plasmid DNA in the reaction accompanied by endogenous substances such as hydrogen peroxide or ascorbic acid. The degradation of the DNA molecule occurred via the free radical mechanism. Calculations based on measured spectra allowed determining the kinetic parameters of OH formation. The cytotoxic effects of Gos and its metallo-derivative were tested in vitro towards two cancer cell lines (A549 - human lung adenocarcinoma, CT26 - mouse colon carcinoma).

The ability of pathogenic bacteria to develop resistance mechanisms to avoid the antimicrobial potential of antibiotics has become an increasing problem for the healthcare system. The search for more effective and selective antimicrobial materials, though not harmful to mammalian cells, seems imperative. Herein we propose the use of gold-chitosan nanocomposites as effective bactericidal materials avoiding damage to human cells. Nanocomposites were obtained by taking advantage of the reductive and stabilizing action of chitosan solutions on two different gold precursor concentrations. The resulting nanocomposites were added at different final concentrations to a coculture model formed by Gram-positive (Staphylococcus aureus) or Gram-negative (Escherichia coli) bacteria and human macrophages. Gold-chitosan colloids exhibited superior bactericidal ability against both bacterial models without showing cytotoxicity on human cells at the concentrations tested. Morphological and in vitro viability studies supported the feasibility of the infection model here described to test novel bactericidal nanomaterials. Flow cytometry and scanning electron microscopy analyses pointed to the disruption of the bacterial wall as the lethal mechanism. Data obtained in the present study suggest that gold-chitosan nanocomposites are powerful and promising nanomaterials for reducing bacteria-associated infections, respecting the integrity of mammalian cells, and displaying high selectivity against the studied bacteria.

The emergence of Multi-Drug-Resistant (MDR) organisms has become a major worldwide clinical problem. The extensive and routine use of the first-line antibiotics to control infections imposed the development of multiple mechanisms of microbial resistance. Despite the fact that numerous advanced technologies enable the molecular design of new antibiotics, the MDR-associated infections remain a great challenge to modern medicine. Consequently, there is an urgent need to find other methods for reducing the antimicrobial resistance problem. Innovative bioinorganic antimicrobial platforms offer an interesting alternative for combating the microbial resistance. Herein, we describe the bioinorganic strategies with multiple mechanisms of action based on i) small metal complexes, ii) metal modified macromolecules, iii) metal and metal oxides nanoparticles, iv) light-activated bioinorganic platforms, to overcome the pathogen's resistance.

Alginate nanofibers were prepared in the presence of poly(ethylene oxide) (PEO), a surfactant Pluronic F-127, and a model drug (ciprofloxacin hydrochloride, CpHCl), all mixed prior to electrospinning. It was demonstrated that addition of a carrier polymer (PEO) and a small amount of surfactant are necessary to obtain uniform alginate fibers with cylindrical shape and regular morphology. Importantly, PEO was completely removed from the resulting nanofibers during cross-linking and stabilization post-treatment. The stable alginate fibers loaded with CpHCl were examined by scanning electron microscopy and the average diameter of the fibers ranged from 109 nm (unloaded fibers) to 161 nm (loaded fibers). The release of a studied antibiotic from the nanofibers, characterized by a final loading efficiency of 51%, was tested in physiological conditions. It was revealed that ca. 24% of CpHCl is released during first 20 h with combined transport mechanism, however with the predominant contribution of Fickian diffusion.

In this work, alginate beads loaded with ciprofloxacin (AL_CP) and alginate beads loaded with ciprofloxacin and covered by chitosan (AL_CP_CS) were prepared by emulsification technique in combination with internal gelation method. Physicochemical characterization of the resulting formulations revealed the hydrodynamic diameter and Zeta potential ca. 160 nm and ca. −32 mV in the case of AL_CP and ca. 240 nm and ca. +14 mV in the case of AL_CP_CS (pH = 6.0), respectively. Kinetics of ciprofloxacin release from alginate/chitosan formulations was studied in different media (pH = 1.2, 6.8, and 7.4). Covering alginate core with a polycation such as chitosan moderates the drug release, resulting in a pH-sensitive hybrid controlled-release system. Herein, alginate beads with encapsulated ciprofloxacin covered with chitosan are proposed as an effective oral delivery system since the drug release from alginate core is limited in low pH solution (gastric conditions).

Surface modification of two titanium alloys (Ti-6Al-4V and γ-TiAl) was performed by Plasma Assisted Microwave Chemical Vapor Deposition (PA MW CVD) method. The plasma treatment revealed formation of stable surface coatings and significant improvement of mechanical and surface parameters such as: hardness, roughness, surface energy and contact angle, that are crucial in case of application in implantology. Deposition of SiCNH coating on the γ-TiAl alloy surface, without plasma nitriding process application, resulted in the most hydrophobic structure with the largest surface area. The selected deposition parameters aided the excellent attachment of CT26 cells and promoted their growth.

Two cuprous complexes with 1-(2-pyridylazo)-2-naphthol (PAN) or 4-(2-pyridylazo)resorcinol (PAR) and triphenylphosphines, [Cu(PAN(PPh_{3})_{2}]BF_{4}(1) and[Cu(PAR)(PPh_{3})_{2}]BF_{4}(2), are described in this work. The structures of both compounds were characterized by NMR and UV–Vis spectroscopies, mass spectrometry, IR-ATR measurements and DFT calculations. The single crystal diffraction of both complexes confirmed that the coordination polyhedrons around the copper centres are distorted tetrahedrons. Interestingly, the PAR and the PAN ligands are not planar in the synthesized complexes. The ligands coordinate to the central copper(I) ions by only two nitrogen atoms: one from pyridine and one from an azo group. The oxygen atoms from the hydroxyl groups do not form bonds with copper, but take part in strong intramolecular hydrogen bonds, which stabilize the conformations of the ligands. It is noteworthy that these bonds have different characters. In complex 2 we observed a typical O–H⋯N hydrogen bond, whereas in complex 1 proton transfer takes place, resulting in O⋯H–N bond formation. DFT data confirm the different characters of the H-bonds observed in the X-ray structures.

Chitosan scaffolds of different deacetylation degrees, average molecular weights and concentrations reinforced with silica nanoparticles were prepared for bone tissue regeneration. The resulting nanocomposites showed similar pore sizes (

In this paper we present lomefloxacin's (HLm, 2nd generation fluoroquinolone antibiotic agent) organic and inorganic derivatives: aminomethyl(diphenyl)phosphine (PLm), its oxide as well as new copper(I) iodide or copper(I) thiocyanate complexes with PLm and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2′-biquinoline (bq) as the auxiliary ligands. The synthesized compounds were fully characterised by NMR, UV–Vis and luminescence spectroscopies. Selected structures were analysed by theoretical DFT (density functional theory) methods. High stability of the complexes in aqueous solutions in the presence of atmosferic oxygen was proven. Cytotoxic activity of all compounds was tested towards three cancer cell lines (CT26 - mouse colon carcinoma, A549 - human lung adenocarcinoma, and MCF7 - human breast adenocarcinoma). All complexes are characterised by cytotoxic activity higher than the activity of the parent drug and its organic derivatives as well as cisplatin. Studied derivatives as well as parent drug do not intercalate to DNA, except Cu(I) complexes with bq ligand. All studied complexes caused single-stranded cleavage of the sugar–phosphate backbone of plasmid DNA. The addition of H2O2 caused distinct changes in the plasmid structure and led to single- and/or double-strain plasmid cleavage. Studied compounds interact with human serum albumin without affecting its secondary structure.

Applications of metalloporphyrins and related molecules have been extensively pursued in the context of photodynamic therapy of cancer (PDT) and other biomedical applications. This review discusses photophysical and photochemical properties of metalloporphyrins and their analogues, such as metallochlorins, metallobacteriochlorins and metallophthalocyanines that are relevant for photodynamic processes. We specially emphasize the search for sensitizers strongly absorbing in phototherapeutic window (650–850 nm), the most penetrating and least harmful radiation to human tissues. Molecular engineering is guided by the understanding of the influence of the central metal ion and substituents on the electronic structure and photophysical properties of these compounds. The effects of the structural modifications are elucidated via studies of the electronic absorption and emission spectra, fluorescence and triplet state lifetimes and quantum yields, as well as quantum yields of singlet oxygen generation. The interaction between electronically excited (metallo)porphyrin derivatives and molecular oxygen is specially highlighted, because it leads to the generation of reactive oxygen species (ROS), the major players in photomedicine and photocatalysis. The parameters analysed and correlated encompass photophysical and electrochemical properties, cellular uptake and localization of the photosensitizer, as well as the mechanism of photodynamically induced cell death. The factors that determine the efficacy of PDT (drug and light doses, drug to light interval, oxygen concentration and tumour margin) are also emphasized. This review explores the most recent research performed on metalloporphyrin-based materials in photodynamic therapy, photodynamic inactivation of microorganisms, photodiagnosis and drug delivery, demonstrating their perspectives for biomedical applications.

Introduction of tertiary aminomethylphosphane P{CH2N(CH2CH2)2NCH2CH3}3 (B; tris{1-[4-ethyl(tetrahydro-1,4-diazino)]methyl}phosphane) to methanolic solution of [Ru(η5-C5H5)Cl(PPh3)2] (1) and NaBF4, instead of straightforward substitution of the chloride leads to concomitant cleavage of aminomethylphosphane’s P CH2 bond. The obtained complex [Ru(η5-C5H5)PH{CH2N(CH2CH2)2NCH2CH3}2(PPh3)2]BF4 (2B′) was fully characterized by spectroscopic methods ((NMR, IR, ESI-MS) and its solid state structure was determined with single crystal X-ray diffraction method. It was proven that the structure of 2B′ is similar to the previously synthesized morpholine counterpart [Ru(η5-C5H5)PH{CH2N(CH2CH2)2O}2(PPh3)2]BF4 (2A′). DFT calculations (B3LYP with the D95V(d,p) basis set for C, N, H and O and LanL2DZ with Los Alamos ECPs for Ru, P and Cl) revealed that the binding of aminomethylphosphanes to the ruthenium centre leads to the P C bonds elongation, which may finally result in breaking one of them and phosphane’s reduction from tertiary to secondary ones.

A lack of an effective way to eliminate pathogenic bacteria hidden in the biofilm is a major problem in the treatment of chronic bacterial infections. Iminosugar derivatives are potential candidates for inhibitors of enzymes taking part in the biosynthesis of exopolysaccharides, which are forming bacterial biofilm. Investigated iminosugars were studied either at an early stage of biofilm formation or later on when the mature biofilm of Pseudomonas aeruginosa was already formed. A series of diverse iminosugar structures significantly inhibited biofilm formation, whereas they showed no influence on already formed biofilm. This indicates a possible mechanism of their action based on inhibition of exopolysaccharide backbone synthesis in the early stages of biofilm formation. Moreover, iminosugar derivatives did not show significant effect on the viable bacterial numbers in both early and mature biofilm forms. Importantly, they were not cytotoxic against human Caco-2 cells in vitro, which may be to their advantage in case of their medical application in preventing P. aeruginosa biofilm formation.