Nanostructured Luminescent Micelles: Efficient “Functional Materials” for Sensing Nitroaromatic and Nitramine Explosives

Luminescent micelles are extensively studied molecular scaffolds used in applied supramolecular chemistry. These are particularly important due to their uniquely organized supramolecular structure and chemically responsive physical and optical features. Various luminescent tags can be incorporated with these amphiphilic micelles to create efficient luminescent probes that can be utilized as “chemical noses” (sensors) for toxic and hazardous materials, bioimaging, drug delivery and transport, etc. Due to their amphiphilic nature and well-defined reorganized self-assembled geometry, these nano-constructs are desirable candidates for size and shape complementary guest binding or sensing a specific analyte. A large number of articles describing micellar fluorogenic probes are reported, which are used for cation/anion sensing, amino acid and protein sensing, drug delivery, and chemo-sensing. However, this particular review article critically summarizes the sensing application of nitroaromatic (e.g., trinitrotoluene (TNT), trinitrobenzene (TNB), trinitrophenol (TNP), dinitrobenzene (DNB), etc.) and nitramine explosives (e.g., 1,3,5-trinitro-1,3,5-triazinane, trivially named as “research department explosive” (RDX), 1,3,5,7-tetranitro-1,3,5,7-tetrazocane, commonly known as “high melting explosive” (HMX) etc.). A deeper understanding on these self-assembled luminescent “functional materials” and the physicochemical behavior in the presence of explosive analytes might be helpful to design the next generation of smart nanomaterials for forensic applications. This review article will also provide a “state-of-the-art” coverage of research involving micellar–explosive adducts demonstrating the intermolecular charge/electron transfer (CT/ET) process operating within the host–guest systems.

ChemSpaX: Exploration of chemical space by automated functionalization of molecular scaffold

Exploration of the local chemical space of molecular scaffolds by post-functionalization (PF) is a promising route to discover novel molecules with desired structure and function. PF with rationally chosen substituents...

2.2 CuAAC in Peptidomimetics and Protein Mimics

The tremendous recent developments in click chemistry, including the impressive developments of strain-promoted cycloaddition reagents, all started with the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction conceived by Meldal et al. and Sharpless et al. This led to a revolution of extremely important applications in the chemical, biological, medical, and materials sciences. It is fair to state that, especially in the synthesis of multifunctional and complex small-to-large biomolecular constructs, CuAAC has been indispensable. This has been particularly evident in the area of peptides, peptidomimetics, and protein mimics. These biomolecules play key roles in the various peptide–peptide, peptide–protein, and protein–protein interactions that are involved in many diseases and disorders, and peptide-based therapeutics can be important in this context. However, it is often important to improve the bioactivity and overall stability, and modulate the spatial structure, of peptide-based therapeutics. The incorporation of the 1,4-disubstituted 1,2,3-triazole moiety as a non-native structural element using CuAAC is explored in this chapter. The resulting incorporated triazole moiety can lead to structural surrogates of the amide bond and disulfide bond. As a consequence, CuAAC can be utilized toward introducing conformational constraints and stabilizing secondary structures of α-helices, β-sheets/turns, or loop-like structures. In addition, CuAAC can be used to combine various peptide sequences with molecular scaffolds to develop protein mimics that can find applications as synthetic vaccines and antibodies.

Triptycene Derivatives: From Their Synthesis to Their Unique Properties

Since the first preparation of triptycene, great progress has been made with respect to its synthesis and the understanding of its properties. Interest in triptycene-based systems is intense; in recent years, advances in the synthetic methodology and properties of new triptycenes have been reported by researchers from various fields of science. Here, an account of these new developments is given and placed in reference to earlier pivotal works that underpin the field. First, we discuss new approaches to the synthesis of new triptycenes. Progress in the regioselective synthesis of sterically demanding systems is discussed. The application of triptycenes in catalysis is also presented. Next, progress in the understanding of the relations between triptycene structures and their properties is discussed. The unique properties of triptycenes in the liquid and solid states are elaborated. Unique interactions, which involve triptycene molecular scaffolds, are presented. Molecular interactions within a triptycene unit, as well as between triptycenes or triptycenes and other molecules, are also evaluated. In particular, the summary of the synthesis and useful features will be helpful to researchers who are using triptycenes as building blocks in the chemical and materials sciences.

Boosting annotation in nutrimetabolomics by Feature-Based Molecular Networking: analytical and computational strategies applied to human urine samples from an untargeted LC-MS/MS based bilberry-blueberry intervention study.

Urine represents a challenging metabolite mixture to decipher. Yet, it contains valuable information on dietary intake patterns as typically investigated using randomized, single-blinded, intervention studies. This research demonstrates how the use of Feature-Based Molecular Networking in combination with public spectral libraries, further expanded with an 'In-house' library of metabolite spectra, improved the non-trivial annotation of metabolites occurring in human urine samples following bilberry and blueberry intake. Following this approach, 65 berry-related and human endogenous metabolites were annotated, increasing the annotation coverage by 72% compared to conventional annotation approaches. Furthermore, the structures of 15 additional metabolites were hypothesized by spectral analysis. Then, by leveraging the MzMine quantitative information, several molecular families of phase II (e.g., glucuronidated phenolics) and phase I (e.g., phenylpropionic acid and hydroxybenzoic acid molecular scaffolds) metabolism were identified by correlation analysis of postprandial kinetics, and the dietary impact of endogenous and exogenous metabolites following bilberry-blueberry intake was estimated.

Design SMAP29-LysPA26 as a Highly Efficient Artilysin against Pseudomonas aeruginosa with Bactericidal and Antibiofilm Activity

Antimicrobial resistance (AMR) is a major issue to global health, particularly the multidrug-resistant (MDR) Gram-negative infections, which pose great challenges. Even new antibiotics research is ongoing, antibiotics used to treat Gram-negative bacteria in the clinical are limited in a small set of molecular scaffolds, and biomolecular categories of antibiotics are urgently needed.

ChemSpaX: Exploration of Chemical Space by Automated Functionalization of Molecular Scaffold

Exploration of the local chemical space of molecular scaffolds by post-functionalization (PF) is a promising route to discover novel molecules with desired structure and function. PF with rationally chosen substituents based on known electronic and steric properties is a commonly used experimental and computational strategy in screening, design and optimization of catalytic scaffolds. Automated generation of reasonably accurate geometric representations of post-functionalized molecular scaffolds is highly desirable for data-driven applications. However, automated PF of transition metal (TM) complexes remains challenging. In this work a Python-based workflow, ChemSpaX, that is aimed at automating the PF of a given molecular scaffold with special emphasis on TMcomplexes, is introduced. In three representative applications of ChemSpaX by comparing with DFT and DFT-B calculations, we show that the generated structures have a reasonable quality for use in computational screening applications. Furthermore, we show thatChemSpaXgenerated geometries can be used in machine learning applications to accurately predict DFT computed HOMO-LUMO gaps for transition metal complexes.ChemSpaXis open-source and aims to bolster and democratize the efforts of the scientific community towards data-driven chemical discovery.

Recent advances in Pd-catalyzed oxidative couplings in the synthesis/functionalization of cyclic scaffolds using molecular oxygen as the sole oxidant

Over the past years, Pd(II)-catalyzed oxidative couplings enabled the achievement of molecular scaffolds with high structural diversity via C−C, C-N and C-O bond-formation reactions. In contrast to the use of stoichiometric amounts of more common oxidants, such as metal salts (Cu and Ag) and benzoquinone derivatives, the use of molecular oxygen in the direct or indirect regeneration of Pd(II) species presents itself as a more viable alternative in terms of economy and sustainability. In this review, we describe recent advances on the development Pd-catalyzed oxidative cyclizations/functionalizations, where molecular oxygen plays a pivotal role as the sole stoichiometric oxidant. 1 Introduction 2 Oxidative C-C and C-Nu Coupling 2.1 Intramolecular Oxidative C-Nu Heterocyclization Reactions 2.1.1 C-H Activation 2.1.2 Wacker/aza-Wacker Type Cyclization 2.1.3 Tandem Wacker/aza-Wacker and Cyclization/Cross Coupling Reactions 2.2 Intermolecular Oxidative C-Nu Heterocoupling Reactions 2.3 Intramolecular Oxidative (C-C) Carbocyclization Reactions 2.4 Intermolecular Oxidative C-C Coupling Reactions 2.4.1 Cyclization Reactions 2.4.2 Cross-Coupling Reactions 2.4.3 Homo-Coupling Reactions 3 Aerobic Dehydrogenative Coupling/Functionalization 4 Oxidative C-H Functionalization 5 Summary

The Fellowship of Privileged Scaffolds—One Structure to Inhibit Them All

Over the past few years, the application of privileged structure has emerged as a powerful approach to the discovery of new biologically active molecules. Privileged structures are molecular scaffolds with binding properties to the range of different biological targets. Moreover, privileged structures typically exhibit good drug-like properties, thus assuring more drug-like properties of modified compound. Our main objective is to discuss the privileged structures used for the development of antiviral agents.