AB569, a nontoxic chemical tandem that kills major human pathogenic bacteria.

Antibiotic-resistant superbug bacteria represent a global health problem with no imminent solutions. Here we demonstrate that the combination (termed AB569) of acidified nitrite (A-NO2-) and Na2-EDTA (disodium ethylenediaminetetraacetic acid) inhibited all Gram-negative and Gram-positive bacteria tested. AB569 was also efficacious at killing the model organism Pseudomonas aeruginosa in biofilms and in a murine chronic lung infection model. AB569 was not toxic to human cell lines at bactericidal concentrations using a basic viability assay. RNA-Seq analyses upon treatment of P. aeruginosa with AB569 revealed a catastrophic loss of the ability to support core pathways encompassing DNA, RNA, protein, ATP biosynthesis, and iron metabolism. Electrochemical analyses elucidated that AB569 produced more stable SNO proteins, potentially explaining one mechanism of bacterial killing. Our data implicate that AB569 is a safe and effective means to kill pathogenic bacteria, suggesting that simple strategies could be applied with highly advantageous therapeutic/toxicity index ratios to pathogens associated with a myriad of periepithelial infections and related disease scenarios.

Oxidation of alkyl benzenes by a flavin photooxidation catalyst on nanostructured metal-oxide films.

We describe here a surface-bound, oxide-based procedure for the photooxidation of a family of aromatic hydrocarbons by a phosphate-bearing flavin mononucleotide (FMN) photocatalyst on high surface area metal-oxide films.

Direct observation of light-driven, concerted electron-proton transfer.

The phenols 4-methylphenol, 4-methoxyphenol, and N-acetyl-tyrosine form hydrogen-bonded adducts with N-methyl-4, 4'-bipyridinium cation (MQ+) in aqueous solution as evidenced by the appearance of low-energy, low-absorptivity features in UV-visible spectra. They are assigned to the known examples of optically induced, concerted electron-proton transfer, photoEPT. The results of ultrafast transient absorption measurements on the assembly MeOPhO-H---MQ+ are consistent with concerted EPT by the instantaneous appearance of spectral features for MeOPhO·---H-MQ+ in the transient spectra at the first observation time of 0.1 ps. The transient decays to MeOPhO-H---MQ+ in 2.5 ps, accompanied by the appearance of oscillations in the decay traces with a period of ∼1 ps, consistent with a vibrational coherence and relaxation from a higher υ(N-H) vibrational level or levels on the timescale for back EPT.

Direct Evidence of a Tryptophan Analogue Radical Formed in a Concerted Electron-Proton Transfer Reaction in Water.

Proton-coupled electron transfer (PCET) is a fundamental reaction step of many chemical and biological processes. Well-defined biomimetic systems are promising tools for investigating the PCET mechanisms relevant to natural proteins. Of particular interest is the possibility to distinguish between stepwise and concerted transfer of the electron and proton, and how PCET is controlled by a proton acceptor such as water. Thus, many tyrosine and phenolic derivatives have been shown to undergo either stepwise or concerted PCET, where the latter process is defined by simultaneous tunneling of the electron and proton from the same transition state. For tryptophan instead, it is theoretically predicted that a concerted pathway can never compete with the stepwise electron-first mechanism (ETPT) when neat water is the primary proton acceptor. The argument is based on the radical pK(a) (∼4.5) that is much higher than that for water (pK(a)(H3O(+)) = 0), which thermodynamically disfavors a concerted proton transfer to H2O. This is in contrast to the very acidic radical cation of tyrosine (pK(a) ∼ -2). However, in this study we show, by direct time-resolved absorption spectroscopy on two [Ru(bpy)3](2+)-tryptophan (bpy = 2,2'-bipyridine) analogue complexes, that also tryptophan oxidation with water as a proton acceptor can occur via a concerted pathway, provided that the oxidant has weak enough driving force. This rivals the theoretical predictions and suggests that our current understanding of PCET reactions in water is incomplete.

Click synthesized dianthryl-TTFV: an efficient fluorescent turn-on probe for transition metal ions.

Tetrathiafulvalene vinylogue (TTFV) was functionalized with two anthryl fluorophores via Cu(I)-catalyzed alkyne-azide [3 + 2] cycloaddition, forming a dianthryl-TTFV hybrid to show fluorescent turn-on sensing behaviour for Cu(2+), Fe(2+), and Cd(2+) ions in THF with remarkably low detection limit down to the sub-ppm level.

Highly sensitive detection of saccharides under physiological conditions with click synthesized boronic acid-oligomer fluorophores.

Two phenylboronic acid based saccharide sensors bearing conjugated oligomer fluorophores with linear and cruciform π-frameworks were synthesized in a modular approach utilizing a Cu-catalyzed alkyne azide cycloaddition (click) reaction. The cruciform fluorophore showed excellent saccharide sensing function under physiological conditions in the mM range, whereas the linear fluorophore gave very limited sensing functions. The different fluorescent sensing behaviours highlight the important role of oligomer fluorophore in the development of effective saccharide sensors.

Marcus-type driving force correlations reveal the mechanism of proton-coupled electron transfer for phenols and [Ru(bpy)3]3+ in water at low pH.

Proton-coupled electron transfer (PCET) from tyrosine and other phenol derivatives in water is an important elementary reaction in chemistry and biology. We examined PCET between a series of phenol derivatives and photogenerated [Ru(bpy)3]3+ in low pH (≤4) water using the laser flash-quench technique. From an analysis of the kinetic data using a Marcus-type free energy relationship, we propose that our model system follows a stepwise electron transfer-proton transfer (ETPT) pathway with a pH independent rate constant at low pH in water. This is in contrast to the concerted or proton-first (PTET) mechanisms that often dominate at higher pH and/or with buffers as primary proton acceptors. The stepwise mechanism remains competitive despite a significant change in the pKa and redox potential of the phenols which leads to a span of rate constants from 1 × 105 to 2 × 109 M-1 s-1. These results support our previous studies which revealed separate mechanistic regions for PCET reactions and also assigned phenol oxidation by [Ru(bpy)3]3+ at low pH to a stepwise PCET mechanism.

Concise, aromatization-based approach to an elaborate C2-symmetric pyrenophane.

A very short synthesis (5 steps), the crystal structure and resolution of an elaborate, inherently chiral [n](1,6)pyrenophane is reported. The synthesis hinges upon two very productive events: a multicomponent reaction and an unprecedented double-McMurry/valence isomerization/dehydrogenation step. Aromatization reactions are involved in the formation of all four of the rings of the pyrene system.

Click functionalized poly(p-phenylene ethynylene)s as highly selective and sensitive fluorescence turn-on chemosensors for Zn2+ and Cd2+ ions.

Side-chain functionalized poly(p-phenylene ethynylene)s (PPEs) carrying triazole linkers, amino donors/receptors, and solubilizing groups have been found to yield remarkably high efficiency of fluorescence turn-on sensing for Zn(2+) and Cd(2+) ions in THF, and for H(+) and Cd(2+) ions in water.

1,8-Pyrenylene-ethynylene macrocycles.

A concise, highly regioselective synthesis of 1,8-dibromo-4,5-dialkoxypyrenes has been developed and exploited in the synthesis of some 1,8-pyrenylene-ethynylene macrocycles. The (1)H NMR data and NICS calculations indicate that there is little or no macrocyclic ring current. Concentration-dependent UV-visible studies indicate no aggregation at low concentration, but 8b forms dimers with voids suitable for intercalation of small molecules in the solid state.

Biscrown-annulated TTFAQ-dianthracene hybrid: synthesis, structure, and metal ion sensing.

A new fluorescence chemosensor (3) made up of a biscrown-annulated TTFAQ receptor and two anthracene fluorophores was designed and synthesized. Its solid-state structure was disclosed by X-ray crystallographic analysis, while fluorescence titrations indicated a high sensitivity for large hard metal cations such as Ba(2+).