Silver Coordination Polymers Driven by Adamantoid Blocks for Advanced Antiviral and Antibacterial Biomaterials.

The development of sustainable biomaterials and surfaces to prevent the accumulation and proliferation of viruses and bacteria is highly demanded in healthcare areas. This study describes the assembly and full characterization of two new bioactive silver(I) coordination polymers (CPs) formulated as [Ag(aca)(µ-PTA)]n·5nH2O (1) and [Ag2(µ-ada)(µ3-PTA)2]n·4nH2O (2). These products were generated by exploiting a heteroleptic approach based on the use of two different adamantoid building blocks, namely 1,3,5-triaza-7-phosphaadamantane (PTA) and 1-adamantanecarboxylic (Haca) or 1,3-adamantanedicarboxylic (H2ada) acids, resulting in the assembly of 1D (1) and 3D (2). Antiviral, antibacterial, and antifungal properties of the obtained compounds were investigated in detail, followed by their incorporation as bioactive dopants (1 wt %) into hybrid biopolymers based on acid-hydrolyzed starch polymer (AHSP). The resulting materials, formulated as 1@AHSP and 2@AHSP, also featured (i) an exceptional antiviral activity against herpes simplex virus type 1 and human adenovirus (HAd-5) and (ii) a remarkable antibacterial activity against Gram-negative bacteria. Docking experiments, interaction with human serum albumin, mass spectrometry, and antioxidation studies provided insights into the mechanism of antimicrobial action. By reporting these new silver CPs driven by adamantoid building blocks and the derived starch-based materials, this study endows a facile approach to access biopolymers and interfaces capable of preventing and reducing the proliferation of a broad spectrum of different microorganisms, including bacteria, fungi, and viruses.

Design, Synthesis, and Anti-Cancer Evaluation of Novel Water-Soluble Copper(I) Complexes Bearing Terpyridine and PTA Ligands.

This study presents a simple and energy-efficient self-assembly LAG synthetic method for novel water-soluble copper(I) complexes [Cu(terpy)(PTA)][PF6] (1) and [Cu(terpy)(PTA)2][PF6] (2). They were characterized by FT-IR, 1H, and 31P{1H} NMR spectroscopy, elemental analysis, and single-crystal/powder X-ray diffraction (for 2). The X-ray analysis of compound 2 indicates a bidentate coordination mode of terpyridine to the metal center. Variable-temperature NMR tests indicate dynamic properties for terpyridine in the case of both compounds, as well as for the PTA ligands in the case of 2. Additionally, compounds 1 and 2 exhibit interesting cytotoxic activity, which was tested on normal human dermal fibroblasts (NHDFs), human lung carcinoma (A549), human breast adenocarcinoma (MCF-7), and human cervix carcinoma (HeLa) established cell lines. In comparison to the other tested compounds, complexes 1 and 2 seem to have significantly lower IC50 values against cancer cells (A549, HeLa, MCF-7), indicating their potential as prospective anticancer agents. Moreover, both compounds show no significant toxicity towards normal skin cells (NHDFs), suggesting a certain selectivity in their action on cancer cells. Cisplatin as a reference compound also exhibited considerable cytotoxicity against cancer cells but with a low level of selectivity, which could lead to unwanted effects on normal cells. Remarkably, compounds 1 and 2 exhibit up to 30 times the cytotoxic activity of cisplatin, with a six-fold lower toxicity to normal cells. They also interact strongly with human serum albumin, suggesting potential therapeutic applications. Overall, these compounds hold significant promise as potential chemotherapeutic agents.

Strategy for an Effective Eco-Optimized Design of Heteroleptic Cu(I) Coordination Polymers Exhibiting Thermally Activated Delayed Fluorescence.

The new series of copper(I) coordination polymers [Cu(N-N)(µ-PTA)]n[PF6]n {N-N = dmbpy (1), bpy (2), ncup (3), and phen (4)} were generated by straightforward reaction in solution or through a mechanochemical route, of [Cu(MeCN)4][PF6] with 1,3,5-triaza-7-phosphaadamantane (PTA) and the corresponding polypyridines, namely, 5,5'-dimethyl-2,2'-bipyridine (dmbpy), 2,2'-bipyridine (bpy), 2,9-dimethyl-1,10-phenanthroline (ncup), and 1,10-phenanthroline (phen). The compounds were obtained as air-stable solids and fully characterized by IR, NMR spectroscopy, and elemental analyses. The molecular structures were confirmed by single-crystal X-ray diffraction analysis (for 1, 2, and 4), revealing infinite one-dimensional (1D) linear chains driven by µ-PTA N,P-linkers. All tested Cu(I) polymeric compounds show emission at room temperature, which was attributed to thermally activated delayed fluorescence (TADF). Evidence of the involvement of the excited singlet state in the emission process is presented. Comparing the photophysical properties of 1 and 2 as well as 3 and 4, of which 1 and 3 have a stiffened structure, by introducing a methyl group to one of the ligands, we demonstrate how TADF properties depend on molecular rigidity. It is shown that stiffening of the structure reduces the flattening distortion around the Cu(I) center in the 3MLCT state. As a result, the ΔE(S1-T1) energy gap becomes smaller and the fluorescence quantum yield increases without significantly extending the emission lifetime. In particular, the ΔE(S1-T1) values for complexes 1 and 3 are among the shortest reported in the scientific literature, 253 and 337 cm-1, and the TADF lifetimes are τ(300 K) = 5.7 and 4.2 µs, respectively. The fluorescence quantum yields for these complexes are measured to be ΦPL(300 K) = 70 and 80%.

Therapeutic Potential of a Water-Soluble Silver-Diclofenac Coordination Polymer on 3D Pancreatic Cancer Spheroids.

This work describes the traditional wet and green synthetic approaches, structural features, and extensive bioactivity study for a new coordination polymer [Ag(µ-PTA)(Df)(H2O)]n·3nH2O (1) that bears a silver(I) center, a 1,3,5-triaza-phosphaadamantane (PTA) linker, and a nonsteroidal anti-inflammatory drug, diclofenac (Df-). Compared to cisplatin, compound 1 exhibits both anti-inflammatory properties and very remarkable cytotoxicity toward various cancer cell lines with a high value of selectivity index. Additionally, the 3D model representing human pancreas/duct carcinoma (PANC-1) and human lung adenocarcinoma (A549) was designed and applied as a clear proof of the remarkable therapeutic potential of 1. The obtained experimental data indicate that 1 induces an apoptotic pathway via reactive oxygen species generation, targeting mitochondria due to their membrane depolarization. This study broadens a group of bioactive metal-organic networks and highlights the significant potential of such compounds in developing advanced therapeutic solutions.

Self-Assembly and Multifaceted Bioactivity of a Silver(I) Quinolinate Coordination Polymer.

Coordination polymers have emerged as a new class of potent biologically active agents due to a variety of important characteristics such as the presence of bioactive metal centers and linkers, low toxicity, stability, tailorable structures, and bioavailability. The research on intermediate metabolites has also been explored with implications toward the development of selective anticancer, antimicrobial, and antiviral therapeutic strategies. In particular, quinolinic acid (H2quin) is a recognized metabolite in kynurenine pathway and potent neurotoxic molecule, which has been selected in this study as a bioactive building block for assembling a new silver(I) coordination polymer, [Ag(Hquin)(µ-PTA)]n·H2O (1). This product has been prepared from silver oxide, H2quin, and 1,3,5-triaza-7-phosphaadamantane (PTA), and fully characterized by standard methods including single-crystal X-ray diffraction. Compound 1 has revealed distinctive bioactive features, namely (i) a remarkable antiviral activity against herpes simplex virus type 1 (HSV-1) and adenovirus 36 (Ad-36), (ii) a significant antibacterial activity against clinically important bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa), and (iii) a selective cytotoxicity against HeLa (human cervix carcinoma) cell line. The present work widens a growing family of bioactive coordination polymers with potent antiviral, antibacterial, and antiproliferative activity.

Antiviral, Antibacterial, Antifungal, and Cytotoxic Silver(I) BioMOF Assembled from 1,3,5-Triaza-7-Phoshaadamantane and Pyromellitic Acid.

The present study reports the synthesis, characterization, and crystal structure of a novel bioactive metal-organic framework, [Ag4(µ-PTA)2(µ3-PTA)2(µ4-pma)(H2O)2]n·6nH2O (bioMOF 1), which was assembled from silver(I) oxide, 1,3,5-triaza-7-phosphaadamantane (PTA), and pyromellitic acid (H4pma). This product was isolated as a stable microcrystalline solid and characterized by standard methods, including elemental analysis, 1H and 31P{1H} NMR and FTIR spectroscopy, and single crystal X-ray diffraction. The crystal structure of 1 disclosed a very complex ribbon-pillared 3D metal-organic framework driven by three different types of bridging ligands (µ-PTA, µ3-PTA, and µ4-pma4-). Various bioactivity characteristics of bioMOF 1 were investigated, revealing that this compound acts as a potent antimicrobial against pathogenic strains of standard Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria, as well as a yeast (Candida albicans). Further, 1 showed significant antiviral activity against human adenovirus 36 (HAdV-36). Finally, bioMOF 1 revealed high cytotoxicity toward an abnormal epithelioid cervix carcinoma (HeLa) cell line with low toxicity toward a normal human dermal fibroblast (NHDF) cell line. This study not only broadens the family of PTA-based coordination polymers but also highlights their promising multifaceted bioactivity.

Synthesis, Structural, and Cytotoxic Properties of New Water-Soluble Copper(II) Complexes based on 2,9-Dimethyl-1,10-Phenanthroline and Their One Derivative Containing 1,3,5-Triaza-7-Phosphaadamantane-7-Oxide.

A series of water-soluble copper(II) complexes based on 2,9-dimethyl-1,10-phenanthroline (dmphen) and mixed-ligands, containing PTA=O (1,3,5-triaza-7-phosphaadamantane-7-oxide) have been synthesized and fully characterized. Two types of complexes have been obtained, monocationic [Cu(NO3)(O-PTA=O)(dmphen)][PF6] (1), [Cu(Cl)(dmphen)2][PF6] (2), and neutral [Cu(NO3)2(dmphen)] (3). The solid-state structures of all complexes have been determined by single-crystal X-ray diffraction. Magnetic studies for the complex 1-3 indicated a very weak antiferromagnetic interaction between copper(II) ions in crystal lattice. Complexes were successfully evaluated for their cytotoxic activities on the normal human dermal fibroblast (NHDF) cell line and the antitumor activity using the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa), colon (LoVo), and breast adenocarcinoma (MCF-7) cell lines. Complexes 1 and 3 revealed lower toxicity to NHDF than A549 and HeLa cells, meanwhile compound 2 appeared to be more toxic to NHDF cell line in comparison to all cancer lines. Additionally, interactions between the complexes and human apo-transferrin (apo-Tf) using fluorescence and circular dichroism (CD) spectroscopy were also investigated. All compounds interacted with apo-transferrin, causing same changes of the protein conformation. Electrostatic interactions dominate in the 1/2 - apo- Tf systems and hydrophobic and ionic interactions in the case of 3.

Pentafluorophenyl Platinum(II) Complexes of PTA and its N-Allyl and N-Benzyl Derivatives: Synthesis, Characterization and Biological Activity.

From the well-known 1,3,5-triaza-phosphaadamantane (PTA, 1a), the novel N-allyl and N-benzyl tetrafuoroborate salts 1-allyl-1-azonia-3,5-diaza-7-phosphaadamantane (APTA(BF4), 1b) and 1-benzyl-1-azonia-3,5-diaza-7-phosphaadamantane (BzPTA(BF4), 1c) were obtained. These phosphines were then allowed to react with (Pt(µ-Cl)(C6F5)(tht))2 (tht = tetrahydrothiophene) affording the water soluble Pt(II) complexes trans-(PtCl(C6F5)(PTA)2) (2a) and its bis-cationic congeners trans-(PtCl(C6F5)(APTA)2)(BF4)2 (2b) and trans-(PtCl(C6F5)(BzPTA)2)(BF4)2 (2c). The compounds were fully characterized by multinuclear NMR, ESI-MS, elemental analysis and (for 2a) also by single crystal X-ray diffraction, which proved the trans configuration of the phosphine ligands. Furthermore, in order to evaluate the cytotoxic activities of all complexes the normal human dermal fibroblast (NHDF) cell culture were used. The antineoplastic activity of the investigated compounds was checked against the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa) and breast adenocarcinoma (MCF-7) cell cultures. Interactions between the complexes and human serum albumin (HSA) using fluorescence spectroscopy and circular dichroism spectroscopy (CD) were also investigated.

Light-stable polypyridine silver(i) complexes of 1,3,5-triaza-7-phosphaadamantane (PTA) and 1,3,5-triaza-7-phosphaadamantane-7-sulfide (PTA[double bond, length as m-dash]S): significant antiproliferative activity of representative examples in aqueous media.

A series of novel silver(i) 2,2':6',2''-terpyridine (tpy), 4'-(4-methylphenyl)-2,2':6':2''-terpyridine (tpy-Ph-Me) and 1,10-phenanthroline-5,6-dione (dione) derivatives containing PTA (1,3,5-triaza-7-phosphaadamantane) or 1,3,5-triaza-7-phosphaadamantane-7-sulfide (PTA[double bond, length as m-dash]S) have been synthesized and fully characterized. Two types of complexes have been obtained, monocationic [Ag(tpy)(PTA)](NO3) (1), [Ag(tpy-Ph-Me)(PTA)](NO3) (2), [Ag(dione)(PTA[double bond, length as m-dash]S)](BF4) (4) and [Ag(dione)2](PF6) (5) and neutral [Ag(dione)(PTA[double bond, length as m-dash]S)(NO3)] (3). The solid-state structures of four complexes have been determined by single-crystal X-ray diffraction. Complexes 1 and 2 are luminescent at room temperature and 77 K while 5 shows emission only at 77 K. Compounds 3 and 4 are not emissive. Furthermore, representative light-stable and water-soluble 1 and 3 were evaluated for their cytotoxic activities on the normal human dermal fibroblast (NHDF) cell line and their antitumor activity using the human lung carcinoma (A549), epithelioid cervix carcinoma (HeLa) and human breast adenocarcinoma (MCF-7) cell lines. Interactions between the complexes and human serum albumin (HSA) using UV-Vis, fluorescence and circular dichroism spectroscopy (CD) were also investigated.

Ru(ii)-(PTA) and -mPTA complexes with N2-donor ligands bipyridyl and phenanthroline and their antiproliferative activities on human multiple myeloma cell lines.

A series of novel ruthenium(ii) 2,2'-bipyridyl (bpy) and 1,10-phenanthroline (phen) derivatives containing PTA (1,3,5-triaza-7-phosphaadamantane) or mPTA (N-methyl-1,3,5-triaza-7-phosphaadamantane cation) have been synthesized and fully characterized. Three types of complexes have been obtained, neutral [Ru(N-N)(PTA)2Cl2] (1, N-N = bpy and 4, N-N = phen), monocationic [Ru(N-N)(PTA)3Cl][Cl] (2, N-N = bpy and 5, N-N = phen) and dicationic [Ru(N-N)(mPTA)Cl2][BF4]2 (3, N-N = bpy and 6, N-N = phen). The solid-state structures of four complexes have been determined by single-crystal X-ray diffraction. The cytotoxicity of the complexes has been evaluated in vitro against U266 and RPMI human multiple myeloma cells.

Syntheses, structures, and antimicrobial activity of new remarkably light-stable and water-soluble tris(pyrazolyl)methanesulfonate silver(I) derivatives of N-methyl-1,3,5-triaza-7-phosphaadamantane salt - [mPTA]BF4.

Two new silver(I) complexes of formula [Ag(mPTA)4](Tpms)4(BF4) (1) and [Ag(Tpms)(mPTA)](BF4) (2) (mPTA = N-methyl-1,3,5-triaza-7-phosphaadamantane cation, Tpms = tris(pyrazol-1-yl)methanesulfonate anion) have been synthesized and fully characterized by elemental analyses, (1)H and (31)P{(1)H} NMR, ESI-MS, and IR spectroscopic techniques. The single-crystal X-ray diffraction study of 1 discloses a noncoordinated nature of the Tpms species, existing as counterions around the highly charged metal center [Ag(mPTA)](5+), 1 being the first reported coordination compound bearing a κ(0)-Tpms. 1 features high solubility and stability in water (S25 °C ≈ 30 mg·mL(-1)). The two complexes interact with calf thymus DNA via intercalation mode, binding to the BSA with decrease of its tryptophan fluorescence with a static quenching mechanism. The two new silver complexes exhibit significant antibacterial and antifungal activities screened in vitro against the standard strains of Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans.

New water-soluble polypyridine silver(I) derivatives of 1,3,5-triaza-7-phosphaadamantane (PTA) with significant antimicrobial and antiproliferative activities.

The new series of silver(I) coordination polymers [Ag(N-N)(µ-PTA)]n(X)n (1, 2, 4-8, 10, 11) and discrete monomers [Ag(N-N)(PTA)2](X) (3, 9) {N-N = bpy (1-3), dtbpy (4), neocup (5, 6), phen (7-9), dione (10, 11); X = NO3 (1, 3, 5, 7, 9, 10), PF6 (2, 4, 6, 8, 11)} were generated by self-assembly reactions, in MeOH at ~25 °C, of AgNO3 or AgPF6 with 1,3,5-triaza-7-phosphaadamantane (PTA) and the corresponding polypyridines, namely 2,2'-bipyridine (bpy), 4,4'-di-tert-butyl-2,2'-bipyridine (dtbpy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neocup) and 1,10-phenanthroline-5,6-dione (dione). The compounds were obtained as air and light stable solids and characterized by IR, (1)H and (31)P{(1)H} NMR spectroscopy, ESI(+)-MS and elemental analyses. The crystal structure of 1 was determined by single crystal X-ray diffraction analysis, revealing infinite one-dimensional (1D) linear chains driven by µ-PTA N,P-linkers. Apart from representing the first examples of the metal-PTA derivatives bearing polypyridine ligands, 1-11 also feature solubility in water (S(25°C) ≈ 4-18 mg mL(-1)). Selected compounds (1, 3, 5, 7, 9 and 10) were thus tested for their biological properties and found to exhibit significant antibacterial and antifungal activities, screened in vitro against the standard strains of Staphylococcus aureus, Staphylococcus pyogenes, Staphylococcus pneumoniae, Staphylococcus sanguinis, Staphylococcus mutans, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. Furthermore, the compounds 5, 7, 9 and 10 show a pronounced antiproliferative activity against human malignant melanoma (A375), and the effects on the inhibition of tumor cells in vitro are in agreement with the DNA-binding studies.

Synthesis, antimicrobial and antiproliferative activity of novel silver(I) tris(pyrazolyl)methanesulfonate and 1,3,5-triaza-7-phosphadamantane complexes.

Five new silver(I) complexes of formulas [Ag(Tpms)] (1), [Ag(Tpms)(PPh(3))] (2), [Ag(Tpms)(PCy(3))] (3), [Ag(PTA)][BF(4)] (4), and [Ag(Tpms)(PTA)] (5) {Tpms = tris(pyrazol-1-yl)methanesulfonate, PPh(3) = triphenylphosphane, PCy(3) = tricyclohexylphosphane, PTA = 1,3,5-triaza-7-phosphaadamantane} have been synthesized and fully characterized by elemental analyses, (1)H, (13)C, and (31)P NMR, electrospray ionization mass spectrometry (ESI-MS), and IR spectroscopic techniques. The single crystal X-ray diffraction study of 3 shows the Tpms ligand acting in the N(3)-facially coordinating mode, while in 2 and 5 a N(2)O-coordination is found, with the SO(3) group bonded to silver and a pendant free pyrazolyl ring. Features of the tilting in the coordinated pyrazolyl rings in these cases suggest that this inequivalence is related with the cone angles of the phosphanes. A detailed study of antimycobacterial and antiproliferative properties of all compounds has been carried out. They were screened for their in vitro antimicrobial activities against the standard strains Enterococcus faecalis (ATCC 29922), Staphylococcus aureus (ATCC 25923), Streptococcus pneumoniae (ATCC 49619), Streptococcus pyogenes (SF37), Streptococcus sanguinis (SK36), Streptococcus mutans (UA159), Escherichia coli (ATCC 25922), and the fungus Candida albicans (ATCC 24443). Complexes 1-5 have been found to display effective antimicrobial activity against the series of bacteria and fungi, and some of them are potential candidates for antiseptic or disinfectant drugs. Interaction of Ag complexes with deoxyribonucleic acid (DNA) has been studied by fluorescence spectroscopic techniques, using ethidium bromide (EB) as a fluorescence probe of DNA. The decrease in the fluorescence of DNA-EB system on addition of Ag complexes shows that the fluorescence quenching of DNA-EB complex occurs and compound 3 is particularly active. Complexes 1-5 exhibit pronounced antiproliferative activity against human malignant melanoma (A375) with an activity often higher than that of AgNO(3), which has been used as a control, following the same order of activity inhibition on DNA, i.e., 3 > 2 > 1 > 5 > AgNO(3)≫ 4.