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Increasingly complex modern gas-monitoring scenarios necessitate advanced sensing capabilities to detect and identify a diverse range of gases under varying conditions. There is a rising demand for individual sensors with multiple responses capable of recognizing gases, identifying components in mixtures, and providing stable responses. Inspired by gas sensors employing multivariable response principles, we develop a nanoporous anodic alumina high-order microcavity (NAA-HOμCV) gas sensor with multiple optical outputs for discriminative gas detection. The NAA-HOμCV architecture, formed by a Fabry–Pérot microcavity with distributed Bragg reflector (DBR) mirrors and an extended-length microcavity layer supporting multiple resonant modes, serves as an effective solid-state fingerprint platform for distinguishing volatile organic compound (VOC) gases. Our research reveals that the coupling strength of light into resonant modes and their evolution depend on the thickness of the DBR mirrors and the dimension of the microcavity layer, which allows us to optimize the discriminative sensing capability of the NAA-HOμCV sensor through structural engineering of the microcavity and photonic crystal mirrors. Gas-sensing experiments conducted on the NAA-HOμCV sensor demonstrate real-time discrimination between physiosorbed VOC gases (isopropanol, ethanol, or acetone) in reversible gas sensing. It also achieves superior ppb-level sensing in irreversible gas sensing of model silane molecules. Our study presents promising avenues for designing compact, cost-effective, and highly efficient gas sensors with tailored properties for discriminative gas detection.

Dendrimers─nanosized macromolecules that can function as hosts for encapsulation of guest molecules─provide new avenues to engineer gain media for lasing systems. In this context, this study investigates the interplay between the geometric features of a model porous scattering medium, nanoporous anodic alumina (NAA), and the chemical features of a model fluorophore–dendrimer encapsulation system to maximize random lasing. The inner surface of the NAA platforms is functionalized with fluorophore molecules encapsulated within dendrimers via an electrostatic interaction. The resulting solid-state composite structures emit well-resolved, intense random lasing when subjected to optical pumping. By engineering fluorophore–dendrimer and geometric features of scattering medium, we can precisely tune the characteristics of random lasing emissions. It is found that lasing structures with low porosity and thickness functionalized with fluorophore molecules encapsulated in second-generation dendrimers provide the best platforms for lasing generation, resulting in a strongly polarized laser at ∼594 nm that has a high quality–gain product of ∼1588 au, a polarization quality of ∼0.86, and a lasing threshold of ∼0.05 mJ pulse–1. Comparative analysis indicates that dendrimers achieve 2.5 times better random lasing than conventional surfactants due to improved encapsulation and minimization of photobleaching. Our results reveal the importance of the fluorophore encapsulation method and design of scattering media in the engineering of random lasing platforms for applications in optical and optoelectrical systems.

The distribution of oxygen and aluminum vacancies across the hemispherical barrier oxide layer (BOL) of nanoporous anodic alumina (NAA) relies intrinsically on the electric field-driven flow of electrolytic species and the incorporation of electrolyte impurities during the growth of anodic oxide through anodization. This phenomenon provides new opportunities to engineer BOL’s inherited ionic current rectification (ICR) fingerprints. NAA’s characteristic ICR signals are associated with the space charge density gradient across BOL and electric field-induced ion migration through hopping from vacancy to vacancy. In this study, we engineer the intrinsic space charge density gradient of the BOL of NAA under a range of anodizing potentials in hard and mild anodization regimes. Real-time characterization of the ICR fingerprints of NAA during selective etching of the BOL makes it possible to unravel the distribution pattern of vacancies through rectification signals as a function of etching direction and time. Our analysis demonstrates that the space charge density gradient varies across the BOL of NAA, where the magnitude and distribution of the space charge density gradient are revealed to be critically determined by anodizing the electrolyte, regime, and potential. This study provides a comprehensive understanding of the engineering of ion transport behavior across blind-hole NAA membranes by tuning the distribution of defects across BOL through anodization conditions. This method has the potential to be harnessed for developing nanofluidic devices with tailored ionic rectification properties for energy generation and storage and sensing applications.

Model light-confining Tamm plasmon cavities based on gold-coated nanoporous anodic alumina photonic crystals (TMM–NAA–PCs) with spectrally tunable resonance bands were engineered. Laplacian and Lorentzian NAA–PCs produced by a modified Gaussian-like pulse anodization approach showed well-resolved, high-quality photonic stopbands, the position of which was precisely controlled across the visible spectrum by the periodicity in the input anodization profile. These PC structures were used as a platform material to develop highly reflective distributed Bragg mirrors, the top sides of which were coated with a thin gold film. The resulting nanoporous hybrid plasmonic–photonic crystals showed strong light-confining properties attributed to Tamm plasmon resonances at three specific positions of the visible spectrum. These structures achieved high sensitivity to changes in refractive index, with a sensitivity of ∼106 nm RIU–1. The optical sensitivity of TMM–NAA–PCs was assessed in real time, using a model chemically selective binding interaction between thiol-containing molecules and gold. The optical sensitivity was found to rely linearly on the spectral position of the Tamm resonance band, for both Laplacian and Lorentzian TMM–NAA–PCs. The density of self-assembled monolayers of thiol-containing analyte molecules formed on the surface of the metallic film directly contributes to the dependence of sensitivity on TMM resonance position in these optical transducers. Our findings provide opportunities to integrate TMM modes in NAA-based photonic crystal structures, with promising potential for optical technologies and applications requiring high-quality surface plasmon resonance bands.

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 fabrication of solid-state single-molecule switches with high on–off conductance ratios has been proposed to advance conventional technology in areas such as molecular electronics. Herein, we employed the scanning tunneling microscope break junction (STM-BJ) technique to modulate conductance in single-molecule junctions using mechanically induced stretching. Compound 1apossesses two dihydrobenzothiophene (DHBT) anchoring groups at the opposite ends linked with rigid alkyne side arms to form a gold–molecule–gold junction, while 1bcontains 4-pyridine-anchoring groups. The incorporation of ferrocene into the backbone of each compound allows rotational freedom to the cyclopentadienyl (Cp) rings to give two distinct conductance states (high and low) for each. Various control experiments and suspended junction compression/retraction measurements indicate that these high- and low-conductance plateaus are the results of conformational changes within the junctions (extended and folded states) brought about by mechanically induced stretching. A high–low switching factor of 42 was achieved for 1a, whereas an exceptional conductance ratio in excess of 2 orders of magnitude (205) was observed for 1b. To the best of our knowledge, this is the highest experimental on–off conductance switching ratio for a single-molecule junction exploiting the mechanically induced STM-BJ method. Computational studies indicated that the two disparate conductance states observed for 1aand 1bresult from mechanically induced conformational changes due to an interplay between conductance and the dihedral angles associated with the electrode–molecule interfaces. Our study reveals the structure–function relationship that determines conductance in such flexible and dynamic systems and promotes the development of a single-molecule variable resistor with high on–off switching factors.

Nanoporous anodic alumina optical microcavities (NAA−μQVs) with spectrally tunable resonance band and surface chemistry are used as model light-confining photonic crystal (PC) platforms to elucidate the combined effect of spectral light confinement features and surface chemistry on optical sensitivity. These model nanoporous PCs show well-resolved, spectrally tunable resonance bands (RBs), the central wavelength of which is engineered from ∼400 to 800 nm by the period of the input anodization profile. The optical sensitivity of the as-produced (hydrophilic) and dichlorodimethylsilane-functionalized (hydrophobic) NAA−μQVs is studied by monitoring dynamic spectral shifts of their RB upon infiltration with organic- and aqueous-based analytical solutions of equally varying refractive index, from 1.333 to 1.345 RIU. Our findings demonstrate that hydrophilic NAA−μQVs show ∼81 and 35% superior sensitivity to their hydrophobic counterparts for organic- and aqueous-based analytical solutions, respectively. Interestingly, the sensitivity of hydrophilic NAA−μQVs per unit of spectral shift is more than 3-fold higher in organic than in aqueous matrices upon equal change of refractive index, with values of 0.347 ± 0.002 and 0.109 ± 0.001 (nm RIU–1) nm–1, respectively. Conversely, hydrophobic NAA−μQVs are found to be slightly more sensitive toward changes of refractive index in aqueous medium, with sensitivities of 0.072 ± 0.002 and 0.066 ± 0.006 (nm RIU–1) nm–1in water- and organic-based analytical solutions, respectively. Our advances provide insights into critical factors determining optical sensitivity in light-confining nanoporous PC structures, with implications across optical sensing applications, and other photonic technologies.

A new class of semiconductor photonic crystals composed of titanium dioxide (TiO2)-functionalized nanoporous anodic alumina (NAA) broadband-distributed Bragg reflectors (BDBRs) for visible-light-driven photocatalysis is presented. NAA–BDBRs produced by double exponential pulse anodization (DEPA) show well-resolved, spectrally tunable, broad photonic stop bands (PSBs), the width of which can be precisely tuned from 70 ± 6 to 153 ± 9 nm (in air) by progressive modification of the anodization period in the input DEPA profile. Photocatalytic efficiency of TiO2–NAA–BDBRs with tunable PSB width upon visible–NIR illumination is studied using three model photodegradation reactions of organics with absorbance bands across the visible spectral regions. Analysis of these reactions allows us to elucidate the interplay of spectral distance between red edge of TiO2–NAA–BDBRs’ PSB, electronic bandgap, and absorbance band of model organics in harnessing visible photons for photocatalysis. Photodegradation reaction efficiency is optimal when the PSB’s red edge is spectrally close to the electronic bandgap of the functional semiconductor coating. Photocatalytic performance decreases dramatically when the red edge of the PSB is shifted toward visible wavelengths. However, a photocatalytic recovery is observed when the PSB’s red edge is judiciously positioned within the proximity of the absorption band of model organics, indicating that TiO2–NAA–BDBRs can harness visible electromagnetic waves to speed up photocatalytic reactions by drastically slowing the group velocity of incident photons at specific spectral regions. Our advances provide new opportunities to better understand and engineer light–matter interactions for photocatalysis, using TiO2–NAA–BDBRs as model nanoporous semiconductor platforms. These high-performing photocatalysts could find broad applicability in visible–NIR light harvesting for environmental remediation, green energy generation, and chemical synthesis.

Understanding and controlling charge transport across multiple parallel molecules are fundamental to the creation of innovative functional electronic components, as future molecular devices will likely be multimolecular. The smallest possible molecular ensemble to address this challenge is a dual-molecule junction device, which has potential to unravel the effects of intermolecular crosstalk on electronic transport at the molecular level that cannot be elucidated using either conventional single-molecule or self-assembled monolayer (SAM) techniques. Herein, we demonstrate the fabrication of a scanning tunneling microscopy (STM) dual-molecule junction device, which utilizes noncovalent interactions and allows for direct comparison to the conventional STM single-molecule device. STM-break junction (BJ) measurements reveal a decrease in conductance of 10% per molecule from the dual-molecule to the single-molecule junction device. Quantum transport simulations indicate that this decrease is attributable to intermolecular crosstalk (i.e., intermolecular π–π interactions), with possible contributions from substrate-mediated coupling (i.e., molecule–electrode). This study provides the first experimental evidence to interpret intermolecular crosstalk in electronic transport at the STM-BJ level and translates the experimental observations into meaningful molecular information to enhance our fundamental knowledge of this subject matter. This approach is pertinent to the design and development of future multimolecular electronic components and also to other dual-molecular systems where such crosstalk is mediated by various noncovalent intermolecular interactions (e.g., electrostatic and hydrogen bonding).

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 1with either Li+, Na+, or Rb+was only slightly greater than that of 1, whereas the conductance of 1with 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.

A platform material composed of 2D gold (Au) nanodot plasmonic single-lattices (Au-nD-PSLs) featuring tailor-engineered geometric features for visible-NIR light-driven enhanced photocatalysis is presented. Au-nD-PSLs efficiently harness incident visible-NIR electromagnetic waves to accelerate photo-chemical reactions by localized surface plasmon resonance (LSPR) effects. Au-nD-PSLs are fabricated by a straightforward, industrially scalable template-assisted approach, using nanopatterned aluminum substrates as templates. The method overcomes the constraints of direct writing lithography and allows Au-nD-PSLs to be transferred to arbitrary functional flexible substrates. Triangular lattice Au-nD-PSLs feature tunable and controllable characteristic LSPR bands across the visible spectrum. Strongly localized electromagnetic fields around Au-nD-PSLs are responsible for the outstanding photocatalytic performance of these plasmonic nanostructures, as demonstrated by finite-difference time-domain simulations and experimental observations. Our approach of rational engineering of LSPR effects in Au-nD-PSLs provides exciting opportunities to develop high-performing and reusable photocatalysts that harvest the visible-NIR spectrum for a broad range of optoelectronic and plasmonic applications.

The primary sequence and secondary structure of a peptide are crucial to charge migration, not only in solution (electron transfer, ET), but also in the solid-state (electron transport, ETp). Hence, understanding the charge migration mechanisms is fundamental to the development of biomolecular devices and sensors. We report studies on four Aib-containing helical peptide analogues: two acyclic linear peptides with one and two electron-rich alkene-based side chains, respectively, and two peptides that are further rigidified into a macrocycle by a side bridge constraint, containing one or no alkene. ETp was investigated across Au/peptide/Au junctions, between 80 and 340 K in combination with the molecular dynamic (MD) simulations. The results reveal that the helical structure of the peptide and electron-rich side chain both facilitate the ETp. As temperature increases, the loss of helical structure, change of monolayer tilt angle, and increase of thermally activated fluctuations affect the conductance of peptides. Specifically, room temperature conductance across the peptide monolayers correlates well with previously observed ET rate constants, where an interplay between backbone rigidity and electron-rich side chains was revealed. Our findings provide new means to manipulate electronic transport across solid-state peptide junctions.

Antibiotic resistance is an urgent threat to global health, with the decreasing efficacy of conventional drugs underscoring the urgency for innovative therapeutic strategies. Antimicrobial peptides present as promising alternatives to conventional antibiotics. Gramicidin S is one such naturally occurring antimicrobial peptide that is effective against Staphylococcus aureus, with a minimum inhibitory concentration (MIC) of 4 μg/mL (3.6 μM). Despite this potent activity, its significant hemolytic toxicity restricts its clinical use to topical applications. Herein, we present rational modifications to the key β-strand and β-turn regions of gramicidin S to concurrently mitigate hemolytic effects, while maintaining potency. Critically, peptide 9displayed negligible hemolytic toxicity, while possessing significant antibacterial potency against a panel of methicillin-sensitive and methicillin-resistant S. aureusclinical isolates (MIC of 8 μg/mL, 7.2 μM). Given the substantial antibacterial activity and near absence of cytotoxicity, 9presents as a potential candidate for systemic administration in the treatment of S. aureusbacteremia/sepsis.

The fields of plasmonics and photonic crystals (PCs) have been combined to generate model light-confining Tamm plasmon (TMM) cavities. This approach effectively overcomes the intrinsic limit of diffraction faced by dielectric cavities and mitigates losses associated with the inherent properties of plasmonic materials. In this study, nanoporous anodic alumina PCs, produced by two-step sinusoidal pulse anodization, are used as a model dielectric platform to establish the methodology for tailoring light confinement through TMM resonances. These model dielectric mirrors feature highly organized nanopores and narrow bandwidth photonic stopbands (PSBs) across different positions of the spectrum. Different types of metallic films (gold, silver, and aluminum) were coated on the top of these model dielectric mirrors. By structuring the features of the plasmonic and photonic components of these hybrid structures, the characteristics of TMM resonances were studied to elucidate effective approaches to optimize the light-confining capability of this hybrid TMM model system. Our findings indicate that the coupling of photonic and plasmonic modes is maximized when the PSB of the model dielectric mirror is broad and located within the midvisible region. It was also found that thicker metal films enhance the quality of the confined light. Gas sensing experiments were performed on optimized TMM systems, and their sensitivity was assessed in real time to demonstrate their applicability. Ag films provide superior performance in achieving the highest sensitivity (S= 0.038 ± 0.001 nm ppm–1) based on specific binding interactions between thiol-containing molecules and metal films.

Here, we report the design, synthesis, and evaluation of a series of inhibitors of Staphylococcus aureusBPL (SaBPL), where the central acyl phosphate of the natural intermediate biotinyl-5′-AMP (1) is replaced by a sulfonamide isostere. Acylsulfamide (6) and amino sulfonylurea (7) showed potent in vitroinhibitory activity (Ki= 0.007 ± 0.003 and 0.065 ± 0.03 μM, respectively) and antibacterial activity against S. aureusATCC49775 with minimum inhibitory concentrations of 0.25 and 4 μg/mL, respectively. Additionally, the bimolecular interactions between the BPL and inhibitors 6and 7were defined by X-ray crystallography and molecular dynamics simulations. The high acidity of the sulfonamide linkers of 6and 7likely contributes to the enhanced in vitroinhibitory activities by promoting interaction with SaBPL Lys187. Analogues with alkylsulfamide (8), β-ketosulfonamide (9), and β-hydroxysulfonamide (10) isosteres were devoid of significant activity. Binding free energy estimation using computational methods suggests deprotonated 6and 7to be the best binders, which is consistent with enzyme assay results. Compound 6was unstable in whole blood, leading to poor pharmacokinetics. Importantly, 7has a vastly improved pharmacokinetic profile compared to that of 6presumably due to the enhanced metabolic stability of the sulfonamide linker moiety.

This is the first work to use a newly designed Li+-selective photoswitchable probe Sabrina Heng Lithium (SHL) in living colon cancer cells to noninvasively monitor cation channel activity in real time by the appearance of lithium hot spots detected by confocal microscopy. Punctate Li+hot spots are clustered in the lamellipodial leading edges of HT29 human colon cancer cells and are colocalized with aquaporin-1 (AQP1) channels. AQP1 is a dual water and cyclic-nucleotide-gated cation channel located in lamellipodia and is essential for rapid cell migration in a subset of aggressive cancers. Both the Li+hot spots and cell migration are blocked in HT29 cells by the AQP1 ion channel antagonist AqB011. In contrast, Li+hot spots are not evident in a poorly migrating colon cancer cell line, SW620, which lacks comparable membrane expression of AQP1. Knockdown of AQP1 by RNA interference in HT29 cells significantly impairs Li+hot spot activity. The SHL probe loaded in living cells shows signature chemical properties of ionic selectivity and reversibility. Dynamic properties of the Li+hot spots, turning on and off, are confirmed by time-lapse imaging. SHL is a powerful tool for evaluating cation channel function in living cells in real time, with particular promise for studies of motile cells or interlinked networks not easily analyzed by electrophysiological methods. The ability to reset SHL by photoswitching allows monitoring of dynamic signals over time. Future applications of the Li+probe could include high-throughput optical screening for discovering new classes of channels, or finding new pharmacological modulators for nonselective cation channels.

This study explores the potential of gold-coated titania-functionalized nanoporous anodic alumina distributed Bragg reflectors (Au-TiO2-NAA-DBRs) as platforms to enhance photocatalytic reactions by integrating “slow photons” and surface plasmon resonance (SPR). The photocatalytic degradation rate of methylene blue – a model organic compound with a well-defined absorption band in the visible spectral region – by these composite photonic crystals (PCs) upon visible-NIR light irradiation is used as an indicator to identify coupling effects between the “slow photon” effect and SPR. Our study demonstrates that the photocatalytic enhancement in Au-TiO2-NAA-DBRs is strongly associated with “slow photon” effect, while the contribution of SPR to the overall photocatalytic enhancement is weak due to the localized generation of surface plasmons on the top surface of the composite PC structure. Photocatalytic enhancement is optimal when the characteristic photonic stopband of these PCs partially overlaps with the absorption band of methylene blue, which results in edges being positioned away from the absorption maximum of the organic dye. The overall photocatalytic degradation for methylene blue is also correlated to the type of noble metal coating and the geometric features of the PC structures. These results establish a rationale for further development of noble metal-coated NAA-based hybrid plasmonic–photonic crystal photocatalyst platforms to optimally integrate “slow photons” and SPR for enhancing the efficiency of photocatalytic reactions and other light harvesting applications.

Many biological processes are driven by the interaction of a host with a guest molecule. We show such interactions can be modulated by carefully defining the local molecular environment to give a specific chemical outcome. Particularly, the selectivity of a host toward two different ions (Ca2+and Al3+) is defined by it being in solution or the physisorbed state. In solution, the host displays greater selectivity toward Ca2+. When physisorbed, the selectivity profile of the host is reversed with enhanced binding of Al3+. This demonstrates a single host molecule can be tailored to selectively bind multiple guests by altering its nanoenvironment.

Molecular electronics is at the forefront of interdisciplinary research, offering a significant extension of the capabilities of conventional silicon-based technology as well as providing a possible stand-alone alternative. Bio-inspired molecular electronics is a particularly intriguing paradigm, as charge transfer in proteins/peptides, for example, plays a critical role in the energy storage and conversion processes for all living organisms. However, the structure and conformation of even the simplest protein is extremely complex, and therefore, synthetic model peptides comprising well-defined geometry and predetermined functionality are ideal platforms to mimic nature for the elucidation of fundamental biological processes while also enhancing the design and development of single-peptide electronic components.

This study reports on the real-time binding assessment between heavy metal ions and blood proteins immobilized onto nanoporous anodic alumina photonic crystals (NAA-PCs) by reflectometric interference spectroscopy (RIfS). The surface of NAA-PCs is chemically functionalized with γ-globulin (GG), transferrin (TFN), and serum albumin (HSA), the major proteins present in human blood plasma. Protein-modified NAA-PC platforms are exposed to analytical solutions of mercury ions of different concentrations. Dynamic changes in the effective optical thickness of protein-modified NAA-PCs in response to heavy metal ions are assessed in real time to evaluate the binding kinetics, affinity, and mechanism. Protein molecules undergo conformational changes upon exposure to mercury ions, with HSA exhibiting the strongest affinity. The combination of protein-modified NAA-PCs with RIfS allows real-time monitoring of protein-heavy metal ions interactions under dynamic flow conditions. This system is capable of detecting dynamic conformational changes in these proteins upon exposure to heavy metal ions. Our results provide new insights into these binding events, which could enable new methodologies to study the toxicity of heavy metal ions and other biomolecular interactions.

In this study, we explore for the first time the capabilities of nanoporous anodic alumina gradient-index filters (NAA-GIFs) functionalized with titanium dioxide (TiO2) photoactive layers to enhance photon-to-electron conversion rates and improve the efficiency of photocatalytic reactions by “slow photon” effect. A set of NAA-GIFs was fabricated by sinusoidal pulse anodization, in which a systematic modification of various anodization parameters (i.e., pore widening time, anodization period, and anodization time) enables the fine-tuning of the photonic stopband (PSB) of these nanoporous photonic crystals (PCs) across the spectral regions. The surface of NAA-GIFs was chemically modified with photoactive layers of TiO2to create a composite photoactive material with precisely engineered optical properties. The photocatalytic performance of TiO2-functionalized NAA-GIFs was assessed by studying the photodegradation of three model organic dyes (i.e., methyl orange, Rhodamine B, and methylene blue) with well-defined absorption bands across different spectral regions under simulated irradiation conditions. Our study demonstrates that when the edges of characteristic PSB of TiO2-modified NAA-GIFs are completely or partially aligned with the absorption band of the organic dyes, the photodegradation rate is enhanced due to “slow photon” effect. A rational design of the photocatalyst material with respect to the organic dye is demonstrated to be optimal to speed up photocatalytic reactions by an efficient management of photons from high-irradiance spectral regions. This provides new opportunities to develop high-performing photocatalytic materials for efficient photocatalysis with broad applicability.

We explore new approaches to engineering the surface chemistry of interferometric sensing platforms based on nanoporous anodic alumina (NAA) and reflectometric interference spectroscopy (RIfS). Two surface engineering strategies are presented, namely (i) selective chemical functionalization of the inner surface of NAA pores with amine-terminated thiol molecules and (ii) selective chemical functionalization of the top surface of NAA with dithiol molecules. The strong molecular interaction of Au3+ions with thiol-containing functional molecules of alkane chain or peptide character provides a model sensing system with which to assess the sensitivity of these NAA platforms by both molecular feature and surface engineering. Changes in the effective optical thickness of the functionalized NAA photonic films (i.e., sensing principle), in response to gold ions, are monitored in real-time by RIfS. 6-Amino-1-hexanethiol (inner surface) and 1,6-hexanedithiol (top surface), the most sensitive functional molecules from approaches i and ii, respectively, were combined into a third sensing strategy whereby the NAA platforms are functionalized on both the top and inner surfaces concurrently. Engineering of the surface according to this approach resulted in an additive enhancement in sensitivity of up to 5-fold compared to previously reported systems. This study advances the rational engineering of surface chemistry for interferometric sensing on nanoporous platforms with potential applications for real-time monitoring of multiple analytes in dynamic environments.

Inverse agonists of peroxisome proliferator activated receptor γ (PPARγ) have emerged as safer alternatives to full agonists for their reduced side effects while still maintaining impressive insulin-sensitizing properties. To shed light on their molecular mechanism, we characterized the interaction of the PPARγ ligand binding domain with SR10221. X-ray crystallography revealed a novel binding mode of SR10221 in the presence of a transcriptionally repressing corepressor peptide, resulting in much greater destabilization of the activation helix, H12, than without corepressor peptide. Electron paramagnetic resonance provided in-solution complementary protein dynamic data, which revealed that for SR10221-bound PPARγ, H12 adopts a plethora of conformations in the presence of corepressor peptide. Together, this provides the first direct evidence for corepressor-driven ligand conformation for PPARγ and will allow the development of safer and more effective insulin sensitizers suitable for clinical use.

Human proliferating cell nuclear antigen (PCNA) is a critical mediator of DNA replication and repair, acting as a docking platform for replication proteins. Disrupting these interactions with a peptidomimetic agent presents as a promising avenue to limit proliferation of cancerous cells. Here, a p21-derived peptide was employed as a starting scaffold to design a modular peptidomimetic that interacts with PCNA and is cellular and nuclear permeable. Ultimately, a peptidomimetic was produced which met these criteria, consisting of a fluorescein tag and SV40 nuclear localization signal conjugated to the N-terminus of a p21 macrocycle derivative. Attachment of the fluorescein tag was found to directly affect cellular uptake of the peptidomimetic, with fluorescein being requisite for nuclear permeability. This work provides an important step forward in the development of PCNA targeting peptidomimetics for use as anti-cancer agents or as cancer diagnostics.

We previously reported potent ligands and inhibitors of Mycobacterium tuberculosisdethiobiotin synthetase (MtDTBS), a promising target for antituberculosis drug development (Schumann et al., ACS Chem Biol. 2021, 16, 2339–2347); here, the unconventional origin of the fragment compound they were derived from is described for the first time. Compound 1(9b-hydroxy-6b,7,8,9,9a,9b-hexahydrocyclopenta[3,4]cyclobuta[1,2-c]chromen-6(6aH)-one), identified by an in silicofragment screen, was subsequently shown by surface plasmon resonance to have dose-responsive binding (KD= 0.6 mM). Clear electron density was revealed in the DAPA substrate binding pocket when 1was soaked into MtDTBS crystals, but the density was inconsistent with the structure of 1. Here, we show that the lactone of 1hydrolyzes to a carboxylic acid (2) under basic conditions, including those of the crystallography soak, with a subsequent ring opening of the component cyclobutane ring forming a cyclopentylacetic acid (3). Crystals soaked directly with authentic 3produced an electron density that matched that of crystals soaked with presumed 1, confirming the identity of the bound ligand. The synthetic utility of fortuitously formed 3enabled the subsequent compound development of nanomolar inhibitors. Our findings represent an example of chemical modification within drug discovery assays and demonstrate the value of high-resolution structural data in the fragment hit validation process.