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Short-chain amphipathic peptides are promising components in the new generation of engineered biomaterials. The model 14-residue leucine-lysine peptide Ac-LKKLLKLLKKLLKL-N[H.sub.2] (LKα) is one such amphipathic peptide. In dilute aqueous solution ( Key words: biomaterials, amphipathic peptide, NMR spectroscopy, circular dichroism spectroscopy, fluorinated alcohols. Resume : Les peptides amphipathiques a chame courte sont des composes tres prometteurs qui font partie de la nouvelle generation de produits issus du genie des biomateriaux. Le peptide modele contenant 14 residus leucine et lysine AcLKKLLKLLKKLLKL-N[H.sub.2] (LKα) est l'un d'entre eux. On a suggere anterieurement, en s'appuyant sur des donnees de spectroscopie DC, qu'en solution aqueuse diluee ( Mots-cles: biomateriaux, peptide amphipathique, spectroscopie RMN, spectroscopie de dichroisme circulaire, alcools fluores., Introduction Peptides play a wide variety of biochemical roles in multicellular organisms, ranging from weapons for antimicrobial destruction (1) to messengers for intercellular communication. (2) Their biological importance is highlighted [...]

Antibiotic resistance is one of the world's most urgent public health problems. Antimicrobial photodynamic therapy (aPDT) is a promising therapy to combat the growing threat of antibiotic resistance. The aPDT combines a photosensitizer and light to generate reactive oxygen species to induce bacterial inactivation. Ruthenium polypyridyl complexes are significant because they possess unique photophysical properties that allow them to produce reactive oxygen species upon photoirradiation, which leads to cytotoxicity. These antimicrobial agents cause bacterial cell death by DNA and cytoplasmic membrane damage. This article presents a comprehensive review of photoactive antimicrobial properties of kinetically inert and labile ruthenium complexes, nanoparticles coupled photoactive ruthenium complexes, and photoactive ruthenium nanoparticles. Additionally, limitations of current ruthenium‐based photoactive antimicrobial agents and future directions for the development of antibiotic‐resistant photoactive antimicrobial agents are discussed. It is important to raise awareness for the ruthenium‐based aPDT agents in order to develop a new class of photoactive metalloantibiotics capable of combating antibiotic resistance. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is one of the world's most urgent public health problems. Antimicrobial photodynamic therapy (aPDT) is a promising therapy to combat the growing threat of antibiotic resistance. The aPDT combines a photosensitizer and light to generate reactive oxygen species to induce bacterial inactivation. Ruthenium polypyridyl complexes are significant because they possess unique photophysical properties that allow them to produce reactive oxygen species upon photoirradiation, which leads to cytotoxicity. These antimicrobial agents cause bacterial cell death by DNA and cytoplasmic membrane damage. This article presents a comprehensive review of photoactive antimicrobial properties of kinetically inert and labile ruthenium complexes, nanoparticles coupled photoactive ruthenium complexes, and photoactive ruthenium nanoparticles. Additionally, limitations of current ruthenium‐based photoactive antimicrobial agents and future directions for the development of antibiotic‐resistant photoactive antimicrobial agents are discussed. It is important to raise awareness for the ruthenium‐based aPDT agents in order to develop a new class of photoactive metalloantibiotics capable of combating antibiotic resistance. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a type of treatment that uses light along with photoactive compounds to treat cancer. Light-activated metal complexes with reduced side effects and increased efficacy are promising anticancer agents for PDT. In this study, the amplification of a 1228 base pair region of plasmid pUC18 DNA was used to assess the impact of the metal complex, [Ru(biq)2(dpp)]2+ (biq = 2,2'-biquinoline, dpp = 2,3-bis(2-pyridyl)pyrazine), on the DNA replication needed for cancer cell proliferation. The metal complex [Ru(biq)2(dpp)]2+ undergoes ligand exchange and binds with DNA upon light activation (λirr ≥ 550 nm). Herein, we report that the complex [Ru(biq)2(dpp)]2+ inhibits DNA amplification of pUC18 DNA upon activation with light under hypoxic conditions, as evaluated by Polymerase Chain Reaction (PCR). Upon addition of increasing concentration of the complex, increased inhibition of DNA amplification was observed when irradiated for 30 minutes with visible light (λirr ≥ 550 nm). The ability of the complex to inhibit DNA amplification was compared with that of a well-known anticancer drug, cisplatin. This unique property of the complex to bind with DNA under hypoxic conditions and inhibit DNA amplification upon light activation makes this a molecule of interest for PDT. [ABSTRACT FROM AUTHOR]

A new bimetallic complex, [Ru(biq)2(dpp)PtCl2](PF6)2 (where biq = 2,2′-biquinoline and dpp = 2,3-bis(2-pyridyl)pyrazine), containing a cis-PtCl2 moiety coupled to a sterically strained Ru(II)-based chromophore was designed, synthesized, and investigated with respect to its spectroscopic, redox, photo-induced ligand exchange, and DNA-interaction properties. The electrochemistry of the designed complex was found to be consistent with the bridging coordination of the dpp ligand and formation of the bimetallic complex. The complex displays intense ligand-based π → π* transitions in the UV region and metal-to-ligand charge-transfer transitions (MLCT) in the visible region. The loss of bridging coordination of the dpp ligand and formation of complexes, [Ru(biq)2(CH3CN)2]2+ and [Pt(dpp)(CH3CN)2]2+ was observed when an acetonitrile solution of the metal complex was irradiated with visible light (λirr ≥ 550 nm). The designed complex displays covalent binding with DNA in dark through the cis-PtCl2 moiety, as confirmed by agarose gel electrophoresis. Upon photoirradiation, the complex dissociates into two DNA-binding moieties and displays covalent binding through: (i) a cis-PtL2 subunit of [Ptdpp(L)2]2+ and (ii) open coordination sites of the ruthenium of [Ru(biq)2(L)2]2+ (L = solvent). The designed complex represents the first Ru(II)Pt(II) complex that undergoes photo-induced ligand exchange and displays multifunctional interactions with DNA upon photoirradiation. [ABSTRACT FROM AUTHOR]

Short-chain amphipathic peptides are promising components in the new generation of engineered biomaterials. The model 14-residue leucine-lysine peptide Ac-LKKLLKLLKKLLKL-NH2 (LKα) is one such amphipathic peptide. In dilute aqueous solution (<0.05 mmol/L), it was previously proposed, using CD spectroscopic data, that LKα existed in a cooperative monomeric (unstructured) - tetrameric (α-helical) equilibrium that shifted towards the tetramer at high NaCl and peptide concentrations. Here, at similar peptide concentrations, CD spectroscopy shows that LKα readily adopts α-helical structure in the presence of 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) with maximal helical character in 20% TFE and ∼10% HFIP ( v/ v). The helical character in fluorinated alcohols suggested by the CD data at low peptide concentrations (0.06 mmol/L) is corroborated at high peptide concentrations (1.5 mmol/L) by NMR NOE data that also show that 1.5 mmol/L LKα is helical in 100% water. Size exclusion chromatography and estimations of rotational correlation times ( τc) showed that the self-assembled LKα complexes contained three to five peptides. Removing the N-terminal acetyl group prevents LKα from forming helices and self-associating at high NaCl and peptide concentrations. This more detailed characterization of the structural and physical properties of LKα over a greater range of peptide concentrations and in the presence of fluorinated alcohols will assist the design of biomaterials containing amphipathic peptides and guide the ability to control self-assembly. [ABSTRACT FROM AUTHOR]

The outer-coordination sphere of enzymes acts to fine-tune the active site reactivity and control catalytic rates, suggesting that incorporation of analogous structural elements into molecular catalysts may be necessary to achieve rates comparable to those observed in enzyme systems at low overpotentials. In this work, we evaluate the effect of an amino acid and dipeptide outer-coordination sphere on [Ni(PPh2NPh-R2)2]2+ hydrogen production catalysts. A series of 12 new complexes containing non-natural amino acids or dipeptides was prepared to test the effects of positioning, size, polarity and aromaticity on catalytic activity. The non-natural amino acid was either 3-( meta- or para-aminophenyl)propionic acid terminated as an acid, an ester or an amide. Dipeptides consisted of one of the non-natural amino acids coupled to one of four amino acid esters: alanine, serine, phenylalanine or tyrosine. All of the catalysts are active for hydrogen production, with rates averaging ∼1000 s−1, 40 % faster than the unmodified catalyst. Structure and polarity of the aliphatic or aromatic side chains of the C-terminal peptide do not strongly influence rates. However, the presence of an amide bond increases rates, suggesting a role for the amide in assisting catalysis. Overpotentials were lower with substituents at the N-phenyl meta position. This is consistent with slower electron transfer in the less compact, para-substituted complexes, as shown in digital simulations of catalyst cyclic voltammograms and computational modeling of the complexes. Combining the current results with insights from previous results, we propose a mechanism for the role of the amino acid and dipeptide based outer-coordination sphere in molecular hydrogen production catalysts. [ABSTRACT FROM AUTHOR]

A series of dipeptide substituted nickel complexes with the general formula, [Ni- (PPh,2NNNA-amino acid/ester2)2 Synthesized and characterized (P2N2 = 1,5-diaza-3,7-diphosphacyclooctane, and the dipeptide consists of the non-natural amino add, 3-(4-aminophenyl)propionic add (NNA), coupled to amino add/ esters = glutamic add, alanine, lysine, and aspartic add). Each of these complexes is an active electro catalyst for Hj production. The effects of the outer-coordination sphere on the catalytic activity for the production of H2 were investigated; specifically, the impact of sterics, the abihty of the side chain or backbone to protonate and the pK values of the amino add side chains were studied by varying the amino acids in the dipeptide. The catalytic rates of the different dipeptide substituted nickel complexes varied by over an order of magnitude. The amino add derivatives display the fastest rates, while esterification of the terminal carboxyiic adds and side chains resulted in a decrease in the catalytic rate by 50--70%, implicating a significant role of protonated sites in the outer-coordination sphere on catalytic activity. For both the amino add and ester derivatives, the complexes with the largest substituents display the festest rates, indicating that catalytic activity is not hindered by steric bulk. These studies demonstrate the significant contribution tliat the outer-coordination sphere can have in tuning the catalytic activity of small molecule hydrogenase mimics. [ABSTRACT FROM AUTHOR]

Abstract: Supramolecular complexes consisting of ruthenium chromophores and a cisplatin unit represent an emerging class of bioactive molecules of interest as anti-cancer agents. Although the ability of Ru(II)/Pt(II) heteronuclear complexes to bind to DNA has been demonstrated, the in vivo activity of these complexes has not yet been reported. In the present work, we report the anti-bacterial activity of the complex [(tpy)RuCl(dpp)PtCl2](PF6) (where dpp=2,3-bis(2-pyridyl)pyrazine, tpy=2,2′:6′,2′′-terpyridine). The impact on bacterial cell growth of exposure to different concentrations of [(tpy)RuCl(dpp)PtCl2](PF6) and cisplatin was studied. The bioactivity of this complex was found to be due to the presence of the cis-PtCl2 moiety, as the monometallic synthon [(tpy)RuCl(dpp)](PF6) did not inhibit bacterial cell growth. [Copyright &y& Elsevier]

Antibiotic resistance is one of the world's most urgent public health problems. Antimicrobial photodynamic therapy (aPDT) is a promising therapy to combat the growing threat of antibiotic resistance. The aPDT combines a photosensitizer and light to generate reactive oxygen species to induce bacterial inactivation. Ruthenium polypyridyl complexes are significant because they possess unique photophysical properties that allow them to produce reactive oxygen species upon photoirradiation, which leads to cytotoxicity. These antimicrobial agents cause bacterial cell death by DNA and cytoplasmic membrane damage. This article presents a comprehensive review of photoactive antimicrobial properties of kinetically inert and labile ruthenium complexes, nanoparticles coupled photoactive ruthenium complexes, and photoactive ruthenium nanoparticles. Additionally, limitations of current ruthenium-based photoactive antimicrobial agents and future directions for the development of antibiotic-resistant photoactive antimicrobial agents are discussed. It is important to raise awareness for the ruthenium-based aPDT agents in order to develop a new class of photoactive metalloantibiotics capable of combating antibiotic resistance., (© 2021 American Society for Photobiology.)

The outer-coordination sphere of enzymes acts to fine-tune the active site reactivity and control catalytic rates, suggesting that incorporation of analogous structural elements into molecular catalysts may be necessary to achieve rates comparable to those observed in enzyme systems at low overpotentials. In this work, we evaluate the effect of an amino acid and dipeptide outer-coordination sphere on [Ni(P(Ph)(2)N(Ph-R)(2))(2)](2+) hydrogen production catalysts. A series of 12 new complexes containing non-natural amino acids or dipeptides was prepared to test the effects of positioning, size, polarity and aromaticity on catalytic activity. The non-natural amino acid was either 3-(meta- or para-aminophenyl)propionic acid terminated as an acid, an ester or an amide. Dipeptides consisted of one of the non-natural amino acids coupled to one of four amino acid esters: alanine, serine, phenylalanine or tyrosine. All of the catalysts are active for hydrogen production, with rates averaging ∼1000 s(-1), 40 % faster than the unmodified catalyst. Structure and polarity of the aliphatic or aromatic side chains of the C-terminal peptide do not strongly influence rates. However, the presence of an amide bond increases rates, suggesting a role for the amide in assisting catalysis. Overpotentials were lower with substituents at the N-phenyl meta position. This is consistent with slower electron transfer in the less compact, para-substituted complexes, as shown in digital simulations of catalyst cyclic voltammograms and computational modeling of the complexes. Combining the current results with insights from previous results, we propose a mechanism for the role of the amino acid and dipeptide based outer-coordination sphere in molecular hydrogen production catalysts., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)