Antimicrobial Potency of Fmoc-Phe-Phe Dipeptide Hydrogels with Encapsulated Porphyrin Chromophores Is a Promising Alternative in Antimicrobial Resistance.

Antimicrobial resistance (AMR) poses a significant global health risk as a consequence of misuse of antibiotics. Owing to the increasing antimicrobial resistance, it became imperative to develop novel molecules and materials with antimicrobial properties. Porphyrins and metalloporphyrins are compounds which present antimicrobial properties especially after irradiation. As a consequence, porphyrinoids have recently been utilized as antimicrobial agents in antimicrobial photodynamic inactivation in bacteria and other microorganisms. Herein, we report the encapsulation of porphyrins into peptide hydrogels which serve as delivery vehicles. We selected the self-assembling Fmoc-Phe-Phe dipeptide, a potent gelator, as a scaffold due to its previously reported biocompatibility and three different water-soluble porphyrins as photosensitizers. We evaluated the structural, mechanical and in vitro degradation properties of these hydrogels, their interaction with NIH3T3 mouse skin fibroblasts, and we assessed their antimicrobial efficacy against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria. We found out that the hydrogels are cytocompatible and display antimicrobial efficiency against both strains with the zinc porphyrins being more efficient. Therefore, these hydrogels present a promising alternative for combating bacterial infections in the face of growing AMR concerns.

Light-induced hydrogen production from water using nickel(II) catalysts and N-doped carbon-dot photosensitizers: catalytic efficiency enhancement by increase of catalyst nuclearity.

Solar energy conversion to chemical energy via light-induced H2O splitting to O2 and H2 is considered to be a promising solution to meet the growing global energy demands. To make this transformation economically viable, it is necessary to develop sustainable photocatalytic systems. Herein, we present an efficient photocatalytic H2 production system which relies on components comprised of low-cost and high-abundance elements. In particular, a series of mononuclear complexes [Ni(LNS)3]- and [Ni(N^N)(LNS)2] and a hexanuclear complex [Ni(LNS)2]6 (N^N = diimine and LNS- = heterocyclic thioamidate with different group-substituents) were synthesized and utilized as catalysts, in combination with N-doped carbon dots as photosensitizer, for efficient H2 evolution from aqueous protons. Differences in H2 production efficiency were observed among the studied Ni(II) catalysts, with complexes bearing ligands with stronger electron-donating ability exhibiting higher catalytic activity. A remarkable catalytic efficiency enhancement was observed for the hexanuclear complex, with catalyst loadings lower than those of the mononuclear Ni(II) complexes, affording TONs >1550 (among the highest values reported for photocatalytic systems of similar type operating in H2O). These data provide an indication of catalytic cooperativity between the metal centers of the hexanuclear complex, and demonstrate the crucial role of atomically precise polynuclear Ni(II) catalysts in light-induced H2 production, a result that can guide future catalyst design towards the development of highly efficient, low-cost and environmentally benign photocatalytic systems.

Delivery of Porphyrins Through Self-Assembling Peptide Hydrogels for Accelerated Healing of Experimental Skin Defects In Vivo.

INTRODUCTION: The care and healing of skin defects resulting from different causes has been the object of research to achieve rapid and complete skin regeneration. Hydrogels have been used for their ability to maintain hydration during wound healing, absorb wound exudate, and cover the underlying tissue without adherence while being transparent. In this study, we evaluated the efficacy of a hydrogel (H) with encapsulated porphyrin (H+P) on a rat model of surgically-induced skin defects. METHODS: Four round 6 mm diameter skin defects were performed under general anesthesia on the dorsal area of 24 three-month-old "Young" and 24 twelve-month-old "Mature" male rats. Each age group was separated into the Control, H, and H+P groups, n=8 each, where no therapy, H, or H+P was respectively applied daily for 20 days. Digital photographs and skin biopsies were taken on the third, seventh, 10th, and 20th postoperative days and evaluated by planimetry, histology, and immunohistochemistry. RESULTS: Planimetry results demonstrated significantly decreased perimeter, diameter, and area measurements (p<0.005) of group H+P compared to Control and H groups on days 10 and 20 in the young rats, while in the mature rats, the significant differences were evident earlier (perimeter third day p<0.05; diameter and area seventh day p<0.05 and p<0.005, respectively vs. H). Granulation and scar tissue formation were also reduced in the H+P groups although they were not statistically significant. CONCLUSIONS: The application of H+P on the skin defects benefited the healing process in both young and mature animal groups, as evidenced by the statistically significant findings of planimetry. The beneficial healing process was more pronounced in the mature animals, both in the level of statistical significance as well as regarding time (evident already on the third day of healing), probably due to porphyrin assisting the reduced healing rate, which is observed in organisms of advanced age.

Pegylated-polycaprolactone nano-sized drug delivery platforms loaded with biocompatible silver(i) complexes for anticancer therapeutics.

Cytotoxic potential of Ag(i) coordination compounds against cancer cells is widely recognized, but their frequently low water solubility and potential adverse interactions of Ag(i) ions in biological media require their incorporation into suitable platforms to ensure effective transport and delivery at target sites. Herein, we developed and evaluated the in vitro cytotoxic activity of a biodegradable copolymer-based nano-sized drug delivery system for three cytotoxically active and lipophillic Ag(i) compounds. In particular, polymer-based nanoparticles of the newly synthesized amphiphilic methoxy-poly(ethylene glycol)-poly(caprolactone) (mPEG-PCL) copolymer were prepared as carriers for [Ag(dmp2SH)(PPh3)2]NO3 (1), [Ag(dmp2SH)(xantphos)]NO3 (2) and [Ag(dmp2S)(xantphos)] (3) (dmP2SH = 4,6-dimethylpyrimidine-2-thiol, xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) which exhibit high cytotoxicity against HeLa cancer cells, while they maintain low toxicity against HDFa normal cells. Taking advantage of the favorable donor-acceptor Lewis acid-base and electrostatic interactions between functional groups of 1-3 and mPEG-PCL copolymer, the formation of [X]@mPEG-PCL (X = 1,2,3) nanoparticles with nearly spherical shape was achieved. Satisfactory loading capacities and encapsulation efficiencies were obtained (13-15% and 80-88%, respectively). Differences in their mean size diameters were observed, revealing a dependence on the individual structural characteristics of the Ag(i) compounds. In vitro release profiles of the nanoparticles showed an initial burst stage, followed by a prolonged release stage extending over 15 days, with their release rates being determined by the mean size of the nanoparticles, as well as the type and crystallinity of the encapsulated Ag(i) compounds. In vitro cytotoxicity studies revealed an increased cytotoxic activity of compounds 1-3 after their encapsulation in mPEG-PCL copolymer against HeLa cells, with the actual concentrations of the loaded compounds responsible for the inhibition of cell viability being reduced by 8 times compared to the compounds in free form. Therefore, the current drug delivery system improves the pharmacokinetic properties of the three cytotoxic and biocompatible Ag(i) compounds, and may be beneficial for future in vivo anticancer treatment.

Controlling Solar Hydrogen Production by Organizing Porphyrins.

In this study, a highly efficient photocatalytic H2 production system is developed by employing porphyrins as photocatalysts. Palladium and platinum tetracarboxyporphyrins (PdTCP and PtTCP) are adsorbed or coadsorbed onto TiO2 nanoparticles (NPs), which act as the electron transport medium and as a scaffold that promotes the self-organization of the porphyrinoids. The self-organization of PdTCP and PtTCP, forming H- and J-aggregates, respectively, is the key element for H2 evolution, as in the absence of TiO2 NPs no catalytic activity is detected. Notably, J-aggregated PtTCPs are more efficient for H2 production than H-aggregated PdTCPs. In this approach, a single porphyrin, which self-organizes onto TiO2 NPs, acts as the light harvester and simultaneously as the catalyst, whereas TiO2 serves as the electron transport medium. Importantly, the concurrent adsorption of PdTCP and PtTCP onto TiO2 NPs results in the most efficient catalytic system, giving a turnover number of 22,733 and 30.2 mmol(H2 ) g(cat)-1 .

Photosensitizers for H2 Evolution Based on Charged or Neutral Zn and Sn Porphyrins.

We report a comparison between a series of zinc and tin porphyrins as photosensitizers for photochemical hydrogen evolution using cobaloxime complexes as molecular catalysts. Among all the chromophores tested, only the positively charged zinc porphyrin, [ZnTMePyP4+]Cl4, and the neutral tin porphyrin derivatives, Sn(OH)2TPyP, Sn(Cl2)TPP-[COOMe]4, and Sn(Cl2)TPP-[PO(OEt)2]4, were photocatalytically active. Hydrogen evolution was strongly affected by the pH value as well as the different concentrations of both the sensitizer and the catalyst. A comprehensive photophysical and electrochemical investigation was conducted in order to examine the mechanism of photocatalysis. The results derived from this study establish fundamental criteria with respect to the design and synthesis of porphyrin derivatives for their application as photosensitizers in photoinduced hydrogen evolution.

Self-assembly of aliphatic dipeptides coupled with porphyrin and BODIPY chromophores.

In this work, the self assembly ability of chromophores covalently linked to aliphatic dipeptides is described. Altering various parameters such as the protecting group, the solvent mixture, the dipeptide and the chromophore resulted in different nanostructures. Interestingly, a peptide-porphyrin hybrid is capable of forming a hydrogel in HFIP-water solvent mixture.

Efficient Light-Driven Hydrogen Evolution Using a Thiosemicarbazone-Nickel (II) Complex.

In the following work, we carried out a systematic study investigating the behavior of a thiosemicarbazone-nickel (II) complex (NiTSC-OMe) as a molecular catalyst for photo-induced hydrogen production. A comprehensive comparison regarding the combination of three different chromophores with this catalyst has been performed, using [Ir(ppy) 2 (bpy)]PF 6 , [Ru(bpy) 3 ]Cl 2 and [ZnTMePy]PCl 4 as photosensitizers. Thorough evaluation of the parameters affecting the hydrogen evolution experiments (i.e., concentration, pH, solvent nature, and ratio), has been performed in order to probe the most efficient photocatalytic system, which was comprised by NiTSC-OMe and [Ir(ppy) 2 (bpy)]PF 6 as catalyst and chromophore, respectively. The electrochemical together with the photophysical investigation clarified the properties of this photocatalytic system and allowed us to propose a possible reaction mechanism for hydrogen production.