Enhancing the Electrochemical Activity of 2D Materials Edges through Oriented Electric Fields.

The edges of 2D materials have emerged as promising electrochemical catalyst systems, yet their performance still lags behind that of noble metals. Here, we demonstrate the potential of oriented electric fields (OEFs) to enhance the electrochemical activity of 2D materials edges. By atomically engineering the edge of a fluorographene/graphene/MoS2 heterojunction nanoribbon, strong and localized OEFs were realized as confirmed by simulations and spatially resolved spectroscopy. The observed fringing OEF results in an enhancement of the heterogeneous charge transfer rate between the edge and the electrolyte by 2 orders of magnitude according to impedance spectroscopy. Ab initio calculations indicate a field-induced decrease in the reactant adsorption energy as the origin of this improvement. We apply the OEF-enhanced edge reactivity to hydrogen evolution reactions (HER) and observe a significantly enhanced electrochemical performance, as evidenced by a 30% decrease in Tafel slope and a 3-fold enhanced turnover frequency. Our findings demonstrate the potential of OEFs for tailoring the catalytic properties of 2D material edges toward future complex reactions.

An enantioselective formal synthesis of thienamycin.

Thienamycin is a carbapenem antibiotic with potent activity against gram-negative and gram-positive bacteria. Due to its promising activity but lack of chemical stability, thienamycin serves as inspiration for new synthetic antibiotic scaffolds. In this study, we report a nine-step enantioselective formal synthesis of thienamycin. Our route utilizes an asymmetric reduction, enabled by NaBH4 and D-tartaric acid, followed by a series of diastereoselective reactions to access the key azetidinone precursor to thienamycin. This azetidinone precursor could be used as an intermediate to further develop and expand the scope of next-generation beta-lactam antibiotic scaffolds.

Total Synthesis of Dynobactin A.

The first total synthesis of the potent antimicrobial agent dynobactin A is disclosed. This synthesis enlists a singular aziridine ring opening strategy to access the two disparate ß-aryl-branched amino acids present within this complex decapeptide. Featuring a number of unique maneuvers to navigate inherently sensitive and epimerizable functional groups, this convergent approach proceeds in only 16 steps (LLS) from commercial materials and should facilitate the synthesis of numerous analogues for medicinal chemistry studies.

Atroposelective Total Synthesis of Darobactin A.

A concise, modular synthesis of the novel antibiotic darobactin A is disclosed. The synthesis successfully forges the hallmark strained macrocyclic ring systems in a sequential fashion. Key transformations include two atroposelective Larock-based macrocyclizations, one of which proceeds with exquisite regioselectivity despite bearing an unprotected alkyne. The synthesis is designed with medicinal chemistry considerations in mind, appending key portions of the molecule at a late stage. Requisite unnatural amino acid building blocks are easily prepared in an enantiopure form using C-H activation and decarboxylative cross-coupling tactics.

Stereoselective Synthesis of the Spirocyclic γ-Lactam Core of the Ansalactams.

Ansalactam A is an ansa macrolide natural product that contains a densely functionalized spiro-γ-lactam core containing three contiguous stereocenters. This unusual motif distinguishes it from other members of this family and represents a significant synthetic challenge. Herein, we report the development of a stereoselective formal [3+2] cycloaddition reaction for the construction of this key spiro-γ-lactam motif for the first time, thereby enabling access to the northern domain of ansalactam A.

Gr/3D-ZnO Nanocomposites as Humidity Sensors with Enhanced Sensing Response.

This work introduces a novel humidity sensor based on a nanocomposite material comprising graphene decorated with three-dimensional flower-like structures of zinc oxide (Gr/3D-ZnO) fabricated via a hydrothermal method with various weight percentages of graphene. The surface structure and morphology of the Gr/3D-ZnO nanocomposite were analyzed using XRD, EDS, SEM, TEM, and Raman spectroscopy. The influence of humidity on the electrical properties of the nanocomposite was also investigated. Experiment results revealed that the nanocomposite with 70 wt% of graphene provided high sensitivity (S = 446) with rapid response times (120 s) and recovery times (160 s). These results demonstrate the excellent potential of the proposed Gr/3D-ZnO nanocomposite in monitoring atmospheric humidity. A discussion on the mechanism underlying the effects of humidity on the Gr/3D-ZnO nanocomposite is also provided.

Leveraging Marine Natural Products as a Platform to Tackle Bacterial Resistance and Persistence.

Antimicrobial resistance to existing antibiotics represents one of the greatest threats to human health and is growing at an alarming rate. To further complicate treatment of bacterial infections, many chronic infections are the result of bacterial biofilms that are tolerant to treatment with antibiotics because of the presence of metabolically dormant persister cell populations. Together these threats are creating an increasing burden on the healthcare system, and a "preantibiotic" age is on the horizon if significant action is not taken by the scientific and medical communities. While the golden era of antibiotic discovery (1940s-1960s) produced most of the antibiotic classes in clinical use today, followed by several decades of limited development, there has been a resurgence in antibiotic drug discovery in recent years fueled by the academic and biotech sectors. Historically, great success has been achieved by developing next-generation variants of existing classes of antibiotics, but there remains a dire need for the identification of novel scaffolds and/or antimicrobial targets to drive future efforts to overcome resistance and tolerance. In this regard, there has been no more valuable source for the identification of antibiotics than natural products, with 69-77% of approved antibiotics either being such compounds or being derived from them.Our group has developed a program centered on the chemical synthesis and chemical microbiology of marine natural products with unusual structures and promising levels of activity against multidrug-resistant (MDR) bacterial pathogens. As we are motivated by preparing and studying the biological effects of these molecules, we are not initially pursuing a biological question but instead are allowing the observed phenotypes and activities to guide the ultimate project direction. In this Account, our recent efforts on the synoxazolidinone, lipoxazolidinone, and batzelladine natural products will be discussed and placed in the context of the field's greatest challenges and opportunities. Specifically, the synoxazolidinone family of 4-oxazolidinone-containing natural products has led to the development of several chemical methods to prepare antimicrobial scaffolds and has revealed compounds with potent activity as adjuvants to treat bacterial biofilms. Bearing the same 4-oxazolidinone core, the lipoxazolidinones have proven to be potent single-agent antibiotics. Finally, our synthetic efforts toward the batzelladines revealed analogues with activity against a number of MDR pathogens, highlighted by non-natural stereochemical isomers with superior activity and simplified synthetic access. Taken together, these studies provide several distinct platforms for the development of novel therapeutics that can add to our arsenal of scaffolds for preclinical development and can provide insight into the biochemical processes and pathways that can be targeted by small molecules in the fight against antimicrobial-resistant and -tolerant infections. We hope that this work will serve as inspiration for increased efforts by the scientific community to leverage synthetic chemistry and chemical microbiology toward novel antibiotics that can combat the growing crisis of MDR and tolerant bacterial infections.

Concise Synthesis and Antimicrobial Evaluation of the Guanidinium Alkaloid Batzelladine D: Development of a Stereodivergent Strategy.

Herein, we describe a stereodivergent route to (±)-batzelladine D (2), (+)-batzelladine D (2), (-)-batzelladine D (2), and a series of stereochemical analogues and explore their antimicrobial activity for the first time. The concise synthetic approach enables access to the natural products in a sequence of 8-12 steps from readily available building blocks. Highlights of the synthetic strategy include gram-scale preparation of a late stage intermediate, pinpoint stereocontrol around the tricyclic skeleton, and a modular strategy that enables analogue generation. A key bicyclic ß-lactam intermediate not only serves as the key controlling element for pyrrolidine stereochemistry but also serves as a preactivated coupling partner to install the ester side chain. The stereocontrolled synthesis allowed for the investigation of the antimicrobial activity of batzelladine D, demonstrating promising activity that is more potent for non-natural stereoisomers.

JPEG2000 still image coding quality.

This work demonstrates the image qualities between two popular JPEG2000 programs. Two medical image compression algorithms are both coded using JPEG2000, but they are different regarding the interface, convenience, speed of computation, and their characteristic options influenced by the encoder, quantization, tiling, etc. The differences in image quality and compression ratio are also affected by the modality and compression algorithm implementation. Do they provide the same quality? The qualities of compressed medical images from two image compression programs named Apollo and JJ2000 were evaluated extensively using objective metrics. These algorithms were applied to three medical image modalities at various compression ratios ranging from 10:1 to 100:1. Following that, the quality of the reconstructed images was evaluated using five objective metrics. The Spearman rank correlation coefficients were measured under every metric in the two programs. We found that JJ2000 and Apollo exhibited indistinguishable image quality for all images evaluated using the above five metrics (r > 0.98, p < 0.001). It can be concluded that the image quality of the JJ2000 and Apollo algorithms is statistically equivalent for medical image compression.

A novel medical image quality index.

A novel medical image quality index using grey relational coefficient calculation is proposed in this study. Three medical modalities, DR, CT and MRI, using 30 or 60 images with a total of 120 images used for experimentation. These images were first compressed at ten different compression ratios (10 ∼ 100) using a medical image compression algorithm named JJ2000. Following that, the quality of the reconstructed images was evaluated using the grey relational coefficient calculation. The results were shown consistent with popular objective quality metrics. The impact of different image aspects on four grey relational coefficient methods were further tested. The results showed that these grey relational coefficients have different slopes but very high consistency for various image areas. Nagai's grey relational coefficient was chosen in this study because of higher calculation speed and sensitivity. A comparison was also made between this method and other windows-based objective metrics for various window sizes. Studies found that the grey relational coefficient results are less sensitive to window size changes. The performance of this index is better than some windows-based objective metrics and can be used as an image quality index.