Reports of NAS RA

Systematic Analysis of the HIV-1 Protease Active-Site Conformational Space Across 690 Crystal Structures

2026-05-08T07:54:02+00:00

Human Immunodeficiency Virus-1 protease (HIV-1 PR) is among the most extensively studied drug targets in the Protein Data Bank (PDB), with more than 600 structural models predominantly derived by X-ray crystallography. This study presents a comprehensive analysis of the binding-site conformational space across the available structural record: 690 crystal structures deposited in the PDB with ≥90% sequence identity and resolution better than or equal to 2.50 Å, of which 684 were successfully featurized by pipeline. The structural dataset covers wild-type enzyme, crystallographic stabilization mutants, drug-resistant variants, and 452 distinct inhibitor binders. Each binding site was featurized as a volume-filling point cloud with six descriptors (electrostatic potential, lipophilicity, and pharmacophoric features) and represented as a geodesic distance matrix with further embedding in spectral distance space. Affinity propagation clustered all pockets into 16 discrete conformational states, with four dominant states accounting for 85% of all structures. The chemical space of the 452 extracted inhibitors is largely continuous, and its partitioning does not correspond to the receptor's conformational landscape; yet the molecular weight of binders correlates with cavity volume: heavier inhibitors disproportionately populate the largest closed-flap state, while lighter molecules favour a distinct, tighter binding envelope. This analysis provides a structural basis and insights for ensemble-based virtual screening, de novo generation of inhibitors, and the systematic interpretation of evidenced structure–ligand data across the HIV-1 PR inhibitor landscape.

Polyiodides of L-ornithine. Discovery of a symmetric (L-Orn(H)-H-L-OrnH) (3+)-cation

2026-06-18T08:48:37+00:00

Two polyiodides of l-ornithine, (l-OrnH₂)(I₃)(I)(I₂) (I) and (l-Orn(H)-H-l-OrnH)(I₃)₃·4H₂O (II) have been synthesized and characterized structurally, by IR, Raman and UV-Vis spectroscopy. Electronic structures of both were determined by quantum chemical calculation based on their structures and bandgaps were measured experimentally as well. Salt (I) is triclinic, space group P1 with two formula units in the unit cell, salt (II) crystallizes in the monoclinic space group C2 with half of formula unit in the asymmetric unit. A symmetric dimeric cation (l-Orn(H)-H-l-OrnH) was observed in the structure of (II) for the first time.

Ni(II)-Mediated Asymmetric Synthesis of a Conjugated Diyne-Containing Non-Proteinogenic Amino Acid via Glaser Heterocoupling

2026-06-24T07:48:44+00:00

Non-proteinogenic amino acids bearing acetylenic motifs are valuable building blocks in medicinal chemistry and chemical biology due to their structural rigidity, synthetic versatility, and biological relevance. Herein, we report an asymmetric synthesis of (S)-2-amino-8-(3,4-dihydroisoquinolin-2(1H)-yl)octa-4,6-diynoic acid using a Belokon Ni(II) square-planar complex as a chiral scaffold. The synthetic route involves the preparation of a propargylglycine-derived Ni(II) complex followed by a Glaser heterocoupling reaction with 2-(prop-2-yn-1-yl)-1,2,3,4-tetrahydroisoquinoline, enabling the stereocontrolled construction of a conjugated diyne side chain. Subsequent acidic hydrolysis of the Ni(II) complex, ion-exchange demineralization, and recrystallization from aqueous ethanol afforded the target non-proteinogenic amino acid in high purity with retention of the (S)-configuration. This work demonstrates the compatibility of oxidative alkyne coupling reactions with Ni(II)-mediated asymmetric amino acid synthesis and expands the synthetic toolbox for accessing structurally complex, acetylenic amino acid derivatives.

Cerium hexaboride catalyst synthesized via microwave-assisted synthesis for aerobic oxidative desulfurization

2026-07-09T14:35:09+00:00

In this study, the catalytic performance of CeB₆, synthesized by a rapid microwave-assisted method, was investigated in the aerobic oxidative desulfurization of dibenzothiophene (DBT), a representative model refractory sulfur compound. Structural characterization confirmed the formation of phase-pure CeB₆ with well-developed crystalline morphology. The CeB₆ catalyst demonstrated high conversion (up to 95%) at a relatively low temperature of 150 °C using only air as an oxidant. These findings provide new insights into the redox functionality of lanthanide hexaborides and their potential as a catalyst for oxidative desulfurization processes.

Overvoltage Elimination of Dual-Branch Series–Parallel Charge Pumps with Thin Oxide Transistors

2026-01-07T09:28:26+00:00

Integrated circuits increasingly rely on on-chip generation of voltage levels beyond the nominal supply. Charge pumps provide this functionality using capacitors and switches, but their boosted internal nodes raise reliability concerns in scaled CMOS technologies, especially in processes offering only thin-oxide devices. Prior studies have shown that aging mechanisms such as bias temperature instability can noticeably alter the output voltage and startup behavior of conventional series-parallel charge pumps. This paper presents an aging-aware series–parallel voltage doubler that mitigates overstress at critical output nodes while preserving the intended voltage-boost operation. The circuit is sized to match the fresh-state characteristics of the reference design, enabling a fair comparison. Simulation results under long-term BTI stress confirm improved stability of the charge-pump behavior with reduced aging-induced drift.

Cancer type specific copy number variants are identical over species borders

2026-04-15T08:51:34+00:00

Over the past two decades, we have studied dozens of murine and a few rat-derived tumor cell lines. While these cell lines are commonly used as models for human cancer, their cytogenetic and genetic properties are not fully understood. Therefore, we characterized approximately 40 rodent cancer cell lines using molecular cytogenetics, including multicolor fluorescence in situ hybridization and array-comparative genomic hybridization. We then in silico translated the observed acquired gains and losses of chromosomal regions into the human genome. During these studies, we found that rodent cancer cell lines carried chromosomal imbalances similar to those observed in human cancer cells. In this review, we discuss the cell lines studied, the percentage of gains and losses that agreed with the corresponding human cancer type, and the human cancer subtypes for which each cell line can serve as a suitable model. Additionally, we discuss the fact that polyploidy can only be reliably accessed by cytogenetics and that male cell lines tend to lose their Y chromosome. Overall, the reviewed findings highlight the need for an in-depth cytogenomic characterization before using a cell line in research. Furthermore, the data support the idea that copy number changes are more important than point mutations, at least in advanced tumors, as they are similar across species boundaries.

Ecology-by-design: process-level toxicity assessment as the compass for a tox-minimized chemical industry

2026-06-04T10:11:01+00:00

Green chemistry has transformed chemical innovation by introducing quantitative metrics. However, favorable values for these metrics do not automatically translate into ecological sustainability. A chemical process comprises a dynamic mixture of reagents, catalysts, solvents, intermediates, byproducts, residual feedstocks, and waste streams, each contributing to its overall toxicological footprint. This review argues that toxicity assessment should shift from a compound-centered perspective to a process-level evaluation that considers how toxicological burden is created, transformed, displaced, concentrated, diluted, or released throughout a process life cycle. We propose an ecology-by-design framework that integrates reaction inventories, toxicological endpoints, new approach methodologies, Life Cycle Assessment, USEtox characterization, safe-and-sustainable-by-design principles, and machine-learning-enabled data infrastructures. The ultimate objective is a chemical industry in which ecological performance is optimized alongside yield, selectivity, productivity, energy use, carbon footprint, and cost.

Green Furanics after the 5-(Hydroxymethyl)furfural Bottleneck: Carbon-Efficient Transformations of Biomass into Molecular Complexity, Functional Materials and Circular Chemical Platforms

2026-06-04T07:39:38+00:00

Furanic molecules obtained by dehydration and upgrading of carbohydrates have become a central chemical language for translating renewable biomass into fuels, polymers, solvents, ionic liquids, pharmaceuticals, adsorbents and aromatic building blocks. Yet the field has reached a stage at which the word 'platform' is no longer sufficient. The current frontier is not simply the preparation of 5-(hydroxymethyl)furfural (HMF), furfural (FF), 2,5-diformylfuran (DFF), 2,5-bis(hydroxymethyl)furan (BHMF) or 2,5-furandicarboxylic acid (FDCA), but the disciplined design of carbon-efficient sequences in which feedstock variability, product instability, separations, toxicity, catalytic durability and end-of-life chemistry are treated as one connected problem. This review develops this unified approach around green furanics after the HMF bottleneck. The literature selected herein is used as a core scaffold for discussion of carbohydrate-to-HMF chemistry, HMF aging and stability, electrochemical and catalytic oxidation, hydrogenation and hydrodeoxygenation, Diels-Alder furan-to-aromatics chemistry, C-H functionalization, materials, antimicrobial and adsorption applications, humins valorization and biodegradation. Placing these studies in a broader contemporary landscape – encompassing HMF electrooxidation, paired electrolysis, PEF scale-up, earth-abundant catalysis, furan-core editing, and circular materials – highlights the next decisive challenges. The review argues that the next decisive advances will come from treating HMF not as a molecule to be isolated at any cost, but as a node in adaptive reaction networks where the best intermediate is selected by stability, reactivity, separation and product function.