Synthetically Tuning the 2‐Position of Halogenated Quinolines: Optimizing Antibacterial and Biofilm Eradication Activities via Alkylation and Reductive Amination Pathways

Agents capable of eradicating bacterial biofilms are of great importance to human health as biofilm‐associated infections are tolerant to our current antibiotic therapies. We have recently discovered that halogenated quinoline (HQ) small molecules are: 1) capable of eradicating methicillin‐resistant Staphylococcus aureus (MRSA), methicillin‐resistant Staphylococcus epidermidis (MRSE) and vancomycin‐resistant Enterococcus faecium (VRE) biofilms, and 2) synthetic tuning of the 2‐position of the HQ scaffold has a significant impact on antibacterial and antibiofilm activities. Here, we report the chemical synthesis and biological evaluation of 39 HQ analogues that have a high degree of structural diversity at the 2‐position. We identified diverse analogues that are alkylated and aminated at the 2‐position of the HQ scaffold and demonstrate potent antibacterial (MIC≤0.39 μm ) and biofilm eradication (MBEC 1.0–93.8 μm ) activities against drug‐resistant Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium strains while demonstrating <5 % haemolysis activity against human red blood cells (RBCs) at 200 μm . In addition, these HQs demonstrated low cytotoxicity against HeLa cells. Halogenated quinolines are a promising class of antibiofilm agents against Gram‐positive pathogens that could lead to useful treatments against persistent bacterial infections.     

A charge iteration-corrected extended-Hückel study of the electronic and spectroscopic properties of conjugated heterocycles

A computationally inexpensive modified extended-Hückel method using coordinates from STO-6G(d,p) geometry optimizations is described and shown to accurately simulate the spectra of conjugated heterocycles. The origins of the natural optical activities of blue indophenines and diheptylindophenines, and several related brown, red, and colorless compounds, were investigated with this method to show how it can be used to examine the changes in spectra and electronic structure that occur with substituent additions and changes. Diheptylindophenines were found to be blue because of absorptions from electronic transitions between spatially congruent π and π* molecular orbitals delocalized across carbon, nitrogen, oxygen, and sulfur atomic orbitals. The effects of conjugated thiophene moieties replacing the isatin moiety β-carbonyls move these absorptions to the blue relative to their locations in n-heptylisatin, and the diheptyl groups move these absorptions slightly to the red relative to indophenines.     

Geometric limits of knot complements, II: graphs determined by their complements

We prove that there are compact submanifolds of the 3-sphere whose interiors are not homeomorphic to any geometric limit of hyperbolic knot complements.     

A New Plethysm Formula for Symmetric Functions

This paper gives a new formula for the plethysm of power-sum symmetric functions and Schur symmetric functions with one part. The form of the main result is that for b,

Use of thin collodion films to prevent recoil-ion contamination of alpha-spectrometry detectors

Recoil ions from alpha-particle emission can contaminate surface-barrier detection systems. This contamination results in increased measurement uncertainty, and may require the replacement of expensive detectors. Disposable thin Collodion films are easily prepared and effectively retard the recoil ions when either directly applied to the surface of alpha-sources or as catcher foils between the source and the detector. The thin films are particularly effective for relatively low-level sources, but can sustain structural damage when exposed to high levels of recoil ions (tens of thousands per second) over extended periods of time.     

HPTLC Determination of Polyaromatic Hydrocarbons in Smokers’ Hair

JPC – Journal of Planar Chromatography – Modern TLC - A method developed for quantitative determination of the total amount of polyaromatic hydrocarbons (PAH) in human hair has been...