Optical Modulation of Antibiotic Resistance by Photoswitchable Cystobactamids

The rise of antibiotic resistance causes a serious health care problem, and its counterfeit demands novel, innovative concepts. The combination of photopharmacology, enabling a light-controlled reversible modulation of drug activity, with antibiotic drug design has led to first photoswitchable antibiotic compounds derived from established scaffolds. In this study, we converted cystobactamids, gyrase-inhibiting natural products with an oligoaryl scaffold and highly potent antibacterial activities, into photoswitchable agents by inserting azobenzene in the N-terminal part and/or an acylhydrazone moiety near the C-terminus, yielding twenty analogs that contain mono- as well as double-switches. Antibiotic and gyrase inhibition properties could be modulated 3.4-fold and 5-fold by light, respectively. Notably, the sensitivity of photoswitchable cystobactamids towards two known resistance factors, the peptidase AlbD and the scavenger protein AlbA, was light-dependent. While irradiation of an analog with an N-terminal azobenzene with 365 nm light led to less degradation by AlbD, the AlbA-mediated inactivation was induced. This provides a proof-of-principle that resistance towards photoswitchable antibiotics can be optically controlled.     

Revisiting the Rate-Limiting Step of the ANS–Protein Binding at the Protein Surface and Inside the Hydrophobic Cavity

8-Anilino-1-naphthalenesulfonic acid (ANS) is used as a hydrophobic fluorescence probe due to its high intensity in hydrophobic environments, and also as a microenvironment probe because of its unique ability to exhibit peak shift and intensity change depending on the surrounding solvent environment. The difference in fluorescence can not only be caused by the microenvironment but can also be affected by the binding affinity, which is represented by the binding constant (K). However, the overall binding process considering the binding constant is not fully understood, which requires the ANS fluorescence binding mechanism to be examined. In this study, to reveal the rate-limiting step of the ANS–protein binding process, protein concentration-dependent measurements of the ANS fluorescence of lysozyme and bovine serum albumin were performed, and the binding constants were analyzed. The results suggest that the main factor of the binding process is the microenvironment at the binding site, which restricts the attached ANS molecule, rather than the attractive diffusion-limited association. The molecular mechanism of ANS–protein binding will help us to interpret the molecular motions of ANS molecules at the binding site in detail, especially with respect to an equilibrium perspective.     

Deterioration of ancient cellulose paper,Hanji: evaluation of paper permanence

Hanji paper, the paper material traditionally used in Korea, is in the focus of the present aging and mechanistic study. As raw materials and historic recipes for paper making are still available for Hanji today, specimen resembling historical material at the point of production can be prepared. While from that starting point, historical material had taken the path of natural aging, newly prepared samples—prepared according to both historic and current recipes—were artificially aged, and both aging modes can be compared. For the first time, an in-depth chemical and mathematical analysis of the aging processes for Hanji is presented. The aging of Hanji paper, resulting in hydrolysis and oxidation processes, was addressed by means of selective fluorescene labeling of oxidized groups in combination with gel permeation chromatography, providing profiles of carbonyl and carboxyl groups relative to the molar mass distribution. Starting Hanji showed the highest molecular weight (>1,400 kDa) ever reported for paper. We have defined two critical parameters for comparison of the paper samples: half-life DP (the time until every chain is split once on average) and life expectancy (the time until an average DP of failure is reached and no further mechanical stress can be tolerated). The two values were determined to be approximately 500 and 4,000 years, respectively, for the Hanji samples, provided there is no UV radiation. The rate of cellulose chain scission under accelerated aging (80 °C, RH 65 %), was about 600 times faster than under natural conditions. In addition, cellulose degradation of Hanji paper under accelerated aging condition was about 2–3 times slower than that of historical rag paper as those used in medieval Europe.     

Electrochemiluminescence Bioassays with a Water‐Soluble Luminol Derivative Can Outperform Fluorescence Assays

The most efficient and commonly used electrochemiluminescence (ECL) emitters are luminol, [Ru(bpy)₃]²⁺, and derivatives thereof. Luminol stands out due to its low excitation potential, but applications are limited by its insolubility under physiological conditions. The water‐soluble m‐carboxy luminol was synthesized in 15 % yield and exhibited high solubility under physiological conditions and afforded a four‐fold ECL signal increase (vs. luminol). Entrapment in DNA‐tagged liposomes enabled a DNA assay with a detection limit of 3.2 pmol L^?1, which is 150 times lower than the corresponding fluorescence approach. This remarkable sensitivity gain and the low excitation potential establish m‐carboxy luminol as a superior ECL probe with direct relevance to chemiluminescence and enzymatic bioanalytical approaches.     

Stabilization and first direct spectroscopic evidence of the o-quinone methide derived from vitamin E

[reaction: see text] The o-quinone methide (2) derived from vitamin E (1) can be stabilized at low temperatures in a complex with the highly polar N-methylmorpholine-N-oxide (5). The lifetime of 2 can thus be prolonged from less than 10 s to several minutes. In the complex formed, 2 adopts a zwitterionic, aromatic structure with the exocyclic methylene group in perpendicular arrangement to the ring plane, stabilized by the negatively charged oxygen in 5.     

CsMBi(3)Te(6) and CsM(2)Bi(3)Te(7) (M = Pb, Sn): new thermoelectric compounds with low-dimensional structures

The new materials CsPbBi(3)Te(6) and CsPb(2)Bi(3)Te(7) were discovered through reactions of CsBi(4)Te(6) with PbTe, whereas the isostructural materials CsSnBi(3)Te(6) and CsSn(2)Bi(3)Te(7) were discovered through corresponding reactions with SnTe. The compounds can also be prepared from stoichiometric mixtures of Cs(2)Te, Pb (Sn), Bi, and Te. The crystal structures show a layered architecture of NaCl-type slabs alternating with layers of Cs atoms. This group of compounds offers a new quaternary system, Cs-M-Bi-Te (M = Pb and Sn), available for thermoelectric investigations, including fine-tuning of compositions and doping.