The hemispherical barrier oxide layer (BOL) closing the bottom tips of hexagonally distributed arrays of cylindrical nanochannels in nanoporous anodic alumina (NAA) membranes is structurally engineered by anodizing aluminum substrates in three distinct acid electrolytes at their corresponding self-ordering anodizing potentials. These nanochannels display a characteristic ionic current rectification (ICR) signal between high and low ionic conduction states, which is determined by the thickness and chemical composition of the BOL and the pH of the ionic electrolyte solution. The rectification efficiency of the ionic current associated with the flow of ions across the anodic BOL increases with its thickness, under optimal pH conditions. The inner surface of the nanopores in NAA membranes was chemically modified with thiol-terminated functional molecules. The resultant NAA-based iontronic system provides a model platform to selectively detect gold metal ions (Au3+) by harnessing dynamic ICR signal shifts as the core sensing principle. The sensitivity of the system is proportional to the thickness of the barrier oxide layer, where NAA membranes produced in phosphoric acid at 195 V with a BOL thickness of 232 ± 6 nm achieve the highest sensitivity and low limit of detection in the sub-picomolar range. This study provides exciting opportunities to engineer NAA structures with tailorable ICR signals for specific applications across iontronic sensing and other nanofluidic disciplines.

The formation of a 2:1 sandwich-type complex of 15-crown-5 with K+ has been previously used for the development of various smart materials and devices through detecting K+-induced changes in absorbance, electrochemical impedance, or fluorescence. However, K+-induced changes in the junction conductance of crown ethers have not been fully addressed at the molecular level. An understanding of such properties would not only advance our fundamental knowledge of electronic transport in crown ethers but also lead to practical conductance-based sensing applications. Here, we synthesized a rigid and structurally well-defined oligo­(phenyleneethynylene) (OPE) molecular wire functionalized with a 15-crown-5 ether moiety (1), to measure conductance in the presence of various metal cations using the STM-BJ technique. The conductance of 1 with either Li+, Na+, or Rb+ was only slightly greater than that of 1, whereas the conductance of 1 with K+ exhibited a significant 4-fold increase over that of 1. Quantum transport calculations confirmed that the K+-induced increase in conductance was due to the formation of a 2:1 sandwich-type supramolecular junction, with a “4-anchor” binding mode, which is the optimal configuration to harness these unique recognition capabilities. Our findings provide a solid foundation for the design of practical molecular electronic components that can be incorporated into novel sensing devices.

Staphylococcus aureus, a key ESKAPE bacteria, is responsible for most blood-based infections and, as a result, is a major economic healthcare burden requiring urgent attention. Here, we report in silico docking, synthesis, and assay of N1-diphenylmethyl triazole-based analogues (7–13) designed to interact with the entire binding site of S. aureus biotin protein ligase (SaBPL), an enzyme critical for the regulation of gluconeogenesis and fatty acid biosynthesis. The second aryl ring of these compounds enhances both SaBPL potency and whole cell activity against S. aureus relative to previously reported mono-benzyl triazoles. Analogues 12 and 13, with added substituents to better interact with the adenine binding site, are particularly potent, with K i values of 6.01 ± 1.01 and 8.43 ± 0.73 nM, respectively. These analogues are the most active triazole-based inhibitors reported to date and, importantly, inhibit the growth of a clinical isolate strain of S. aureus ATCC 49775, with minimum inhibitory concentrations of 1 and 8 μg/mL, respectively.

The penultimate step in the biosynthesis of biotin is the closure of the ureido heterocycle in a reaction requiring a nucleoside triphosphate (NTP). In Mycobacterium tuberculosis this reaction is catalyzed by dethiobiotin synthetase (MtDTBS). MtDTBS is unusual as it can employ multiple (NTPs), with a >100-fold preference for cytidine triphosphate (CTP). Here the molecular basis of NTP binding was investigated using a surface plasmon resonancebased ligand binding assay and X-ray crystallography. The biophysical and structural data revealed two discrete mechanisms by which MtDTBS binds NTPs: (i) A high affinity binding mode employed by CTP (K D 160 nM) that is characterized by a slow dissociation rate between enzyme and ligand (k d 5.3 × 10 −2 s −1 ) and that is defined by an extended network of specific ligand−protein interactions involving both the cytidine and triphosphate moieties and (ii) a low affinity mode employed by the remaining NTPs (K D > 16.5 μM), that is characterized by weak interactions between protein and ligand. Previously intractable structures of MtDTBS in complex with ATP, GTP, UTP, and ITP were obtained to define the molecular basis of the low affinity ligand binding. Anchoring of the triphosphate moiety into the phosphate binding loop of MtDTBS allows the promiscuous utilization of multiple NTPs. Both high and low binding mechanisms showed conserved hydrogen bonding interactions involving the β-phosphate of NTPs and a high-affinity anion binding site within the phosphate binding loop. This study provides insights into enzymes that can likewise utilize multiple NTPs.