Search Results (236)

The design of multitargeted drug candidates has recently emerged as a highly attractive area of research. Numerous heterometallic compounds have been developed to enhance both the biological efficacy and physicochemical properties of monometallic metallodrugs. Combining classical transition metals with established antitumor activity, such as Pt, Ru, and Au, with other metal-based fragments offers the potential to generate complex compounds with improved pharmacokinetic and pharmacodynamic profiles. Incorporating different bioactive metal cations within a single molecular framework may enhance anticancer activity through metal-specific interactions with distinct biological targets or through improved physicochemical characteristics of the resulting heteronuclear complexes. Recent studies have underscored the significant progress and promising impact of this multitargeted strategy, particularly in systems that combine ruthenium with other biologically active metal centers. This approach may enable selective biological targeting and help overcome drug resistance. This review compiles and analyzes reported ruthenium-based heteronuclear complexes, offering a comprehensive and critical assessment of recent advances in the rational design and synthesis of novel multinuclear compounds as potential chemotherapeutic agents. Particular emphasis is placed on understanding structure–activity relationships, mechanistic pathways, and the role of metal–metal and metal–ligand interactions in modulating biological responses. The findings summarized herein highlight the remarkable efficacy of a wide range of multinuclear ruthenium anticancer complexes and support the hypothesis that synergistic and/or cooperative interactions between distinct metal-based fragments can significantly enhance pharmacological performance, including improved selectivity, stability, and cellular uptake. Furthermore, emerging insights into their modes of action, resistance profiles, and potential for targeted delivery underscore their promise as viable alternatives to conventional therapies. Overall, this dynamic and rapidly evolving field is poised to inspire continued interdisciplinary research and drive the development of next-generation metallodrugs with improved therapeutic indices and clinical potential. Full article

Achieving selective cleavage of specific chemical bonds using ultrafast laser pulses remains a central challenge in ultrafast strong-field molecular physics. Here, we theoretically investigate the coherent control of strong-field dissociation of the heteronuclear molecular ion HD⁺ initially prepared in vibrationally excited states driven by an ultrashort pulse with a quadratic spectral phase. Our results reveal a pronounced sensitivity of both the total dissociation probability and the branching ratio (H⁺ + D vs. H + D⁺) to the chirp rate of the laser pulse. To uncover the underlying physical mechanism, we analyze the population dynamics in the coupled $1s\sigma$ and $2p\sigma$ electronic states and identify pronounced Rabi oscillations arising from the coherent interplay between multiphoton excitation and field-induced stimulated emission. By tuning the laser chirp rate, these oscillations can be suppressed via quantum interference, thereby reshaping the dissociation dynamics and significantly enhancing the dissociation probability of the H + D⁺ channel. These findings demonstrate that spectral-phase engineering provides a robust and versatile strategy for selective control of branching ratios in strong-field molecular dissociation. Full article

Developing sensitive and reversible CO sensors requires precise control of material–analyte interactions. Using DFT, we investigate CO sensing on bimetallic (Fe, Pt) anchored on N-doped graphene (TM₂–N₄–C), focusing on active-site density effects. Three densities are considered: low (12.7 Å), medium (8.5 Å), and high (4.2 Å). FePt–N₄–C band gaps exhibit non-monotonic tuning, approaching metallicity at high density. CO chemisorbs on Fe sites, but physisorbs on Pt sites. FePt exhibits stronger synergistic adsorption than homonuclear counterparts. While adsorption generally strengthens with density, spin-polarized calculations qualitatively reorder this trend via spin delocalization. High temperatures drastically improve recovery; low-density FePt–N₄–C reaches 65 s at 498 K. Three design principles emerge: low-density heteronuclear systems for reversible sensing, medium-density high-spin states for ultra-sensitive capture, and high-density configurations for work function sensors. This work establishes active site density as a key electronic and kinetic knob for graphene-based CO sensors. Full article

In this report, we describe the synthesis and full spectroscopic characterization of a previously unreported podophyllotoxin (PTOX) analogue bearing a second 3,4,5-trimethoxyphenyl (TMP) unit at the C-4 position through an ester linkage. This dual-TMP PTOX derivative is obtained from a brominated PTOX intermediate. In this precursor, the bromine atom is located on the TMP aromatic ring at the 2′-position. The new compound was fully characterized by proton (¹H), carbon-13 (¹³C), heteronuclear single-quantum coherence (HSQC), and distortionless enhancement by polarization transfer (DEPT) NMR spectroscopy. Ultraviolet–visible (UV-Vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, mass spectrometry and elemental analysis were also performed to confirm the structure and purity of the synthesized ester derivative. Full article

The mechanism of charge partitioning during Coulomb explosion, especially via charge-asymmetric dissociation (CAD) pathways, remains a key question in strong-field molecular dynamics. We present an experimental and theoretical study of CAD in the heteronuclear diatomic molecule iodine bromide (IBr) driven by 800 nm femtosecond laser pulses. Using dc-sliced ion velocity map imaging, we measured the kinetic energy releases of fragment ions I^p+ (p = 1–4) and Br^q+ (q = 1–3), observing both charge-symmetric (CSD) and charge-asymmetric (CAD) dissociation channels. A unified model combining charge-resonance-enhanced ionization (CREI) with a classical over-the-barrier (COB) picture is introduced, which accounts quantitatively for the observed channels. The findings reveal the correlated electron–nuclear dynamics in IBr during Coulomb explosion, advance the understanding of strong-field dissociation in heteronuclear systems, and contribute to the analysis of ultrafast charge transfer in molecules. Full article

The cyclic adamantane framework possesses unique properties such as bulkiness, symmetry, and high lipophilicity. Research aimed at discovering new pharmaceutical agents within the adamantane series continues. In the present work, a targeted modification was carried out to combine two pharmacophore fragments—adamantane and piperidine—within a single molecule. Based on a series of N-substituted piperidin-4-ones, the corresponding secondary alcohols were obtained by reduction with sodium borohydride in isopropanol and subsequent acylation of these alcohols with adamantane carbonyl chloride yielded the corresponding adamantane-carboxylate esters. The structure of the synthesized compounds was studied by NMR methods, including COSY (¹H-¹H), HMQC (¹H-¹³C) and HMBC (¹H-¹³C) techniques. The values of chemical shifts, multiplicities, and integrated intensities of ¹H and ¹³C signals in one-dimensional NMR spectra were determined. The results of COSY (¹H-¹H), HMQC (¹H-¹³C), and HMBC (¹H-¹³C) revealed homo- and heteronuclear interactions, confirming the structure of the studied compounds. The cytotoxic activities of the synthesized compounds were studied. It was found that the synthesized substituted piperidines bearing an adamantane fragment exhibit in vitro antimicrobial and antifungal activity against museum microbial strains (Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538-P, Candida albicans ATCC 10231, Cryptococcus neoformans) and demonstrate significant advantages over the reference drugs used in clinical practice, such as fluconazole and ampicillin. These compounds are therefore recommended for further in-depth studies. Full article

A novel steviol glycoside, Rebaudioside D17, was identified from the leaf extract of Stevia rebaudiana Bertoni. This compound features a rare β-1→4 glycosidic linkage between two glucose units at the C19 position, distinguishing it from its structural isomer, Rebaudioside D. The aim of this study was to isolate and characterize Rebaudioside D17 and investigate its biosynthetic origin. The compound was isolated and structurally characterized using comprehensive NMR spectroscopy including ¹H, ¹³C, COSY, NOESY, Heteronuclear Single Quantum Coherence–Distortionless Enhancement by Polarization Transfer (HSQC-DEPT), Heteronuclear Multiple Bond Correlation (HMBC), Heteronuclear Single Quantum Coherence–Total Correlated Spectroscopy (HSQC-TOCSY), along with mass spectrometry analysis. A tentative biosynthetic pathway is proposed, involving Rebaudioside E19, a putative intermediate bearing the same β-1→4 glycosidic linkage at C19. Rebaudioside E19 may serve as a common precursor to both Rebaudioside D17 and Rebaudioside U3, a minor steviol glycoside previously reported in Stevia rebaudiana leaf extract, which also contains the same β-1→4 glycosidic linkage. The discovery of Rebaudioside D17 expands the known diversity of steviol glycosides and provides new insights into glycosylation patterns in Stevia rebaudiana, which may support the development and production of novel sweeteners with improved sensory and physicochemical properties. Full article

Procyanidins, a class of substances widely distributed in nature, have attracted the attention of the scientific community due to their bioactive properties, especially with regard to human health. This review is based on an extensive examination of peer-reviewed literature, patents, and clinical trial reports published between 2005 and 2025. From an initial pool of more than 300 documents, 283 studies were selected according to criteria of scientific rigor, methodological clarity, and relevance to the research objectives. A literature search was performed using PubMed, PubChem, Google Scholar, Scopus and ResearchGate employing keywords such as Procyanidins, chemical structure, extraction, and health effects. This article provides a comprehensive overview of current methods for obtaining these compounds, which include both natural sources and synthetic approaches. It provides a concise summary of the molecular structure of procyanidins and emphasizes the importance of understanding their conformational features for predicting biological activity. The challenges of establishing correlations between the structural features of procyanidins and their properties are described. In addition, this article explores the many potential applications of these compounds, spanning both biochemistry and the field of design and synthesis of novel materials. This review provides a comprehensive evaluation of Procyanidins, focusing on their geometrical conformation analysis through advanced NMR spectroscopy techniques including homonuclear correlation (COSY, TOCSY), heteronuclear one-bond (HSQC, HMQC), multiple-bond (HMBC) experiments, and through-space correlation (NOESY) in conjunction with various extraction methodologies. Full article

Metal nanoparticles (NP) are increasingly used in biomedical applications. Among them, silver NPs (AgNPs) are used as active components in antibacterial coatings for wound dressings, medical devices, implants, cosmetics, textiles, and food packaging. On the other hand, AgNPs can be toxic to humans, depending on the dose and route of exposure, as agents delivering silver to cells. The cysteine residues are the primary molecular targets in such exposures, due to the high affinity of Ag⁺ ions to thiol groups. The Endothelial monocyte-activating polypeptide II (EMAP II), a cleaved C-terminal peptide of the intracellular aminoacyl-tRNA synthetase multifunctional protein AIMP1, contains five cysteines exposed at its surface. This prompted the question of whether they can be targeted by Ag⁺ ions present at the AgNPs surface or released from AgNPs in the course of oxidative metabolism of the cell. We explored the interactions between recombinant EMAP II, tRNA, and AgNPs using UV-Vis and fluorescence spectroscopy, providing insight into the effects of AgNPs dissolution kinetics on interaction EMAP II with tRNA. In addition, the EMAP II fragments binding to intact AgNPs were established by heteronuclear ¹H-¹⁵N HSQC spectra utilizing a paramagnetic probe. Structural analysis of the EMAP II reveal that the 3D structure of protein was destabilized (partially denatured) by the binding of Ag⁺ ions released from AgNPs at the most exposed cysteines. Surprisingly, this effect enhanced tRNA affinity to EMAP II, lowering its $K_d$. The course of the EMAP II/tRNA/AgNP reaction was also modulated by other factors, such as the presence of Mg²⁺ ions and TCEP, a thiol-group protector used to mimic the reducing conditions of the cell. Full article

The pH of fruit and vegetable juices is usually around 4.0. To adapt to the pH of fruit and vegetable juices, we developed a highly branched pectin as a natural stabiliser, whose polarity is well suited to conditions under weakly acidic conditions. The pectin content of jujube is high (about 2.0%), in which the polysaccharide content of Muzao (2.0–4.8%) is generally higher than the average value of the jujube. To separate the weak polar pectin in jujube, we extracted the crude polysaccharide (ZMP) with 4 times the volume of alcohol. Then we used Diethylaminoethyl (DEAE) cellulose (DEAE-52) ion-exchange chromatography to separate ZMP, and selected the fraction eluted with 0.2 M NaCl for gel purification to obtain ZMP2. After the hydrolysis of ZMP2 with TFA, four fractions, namely ZMP2n5, ZMP2y5, ZMP2n1, and ZMP2y1, were obtained. The purity, molecular weight, and monosaccharide composition of the above four fractions were determined. It was found that each fraction of ZMP2 contained large amounts of galacturonic acid (GalA) and glucuronic acid (GlcA), indicating that ZMP2 was most likely pectin, making it the natural, polar stabiliser we sought. To further determine the primary structure of ZMP2, we also performed FT-IR spectroscopy; methylation; one-dimensional mapping, including Proton Nuclear Magnetic Resonance (¹H NMR), Carbon-13 Nuclear Magnetic Resonance (¹³C NMR) and Distortionless Enhancement by Polarization Transfer 135 (DEPT 135); and two-dimensional mapping, including Correlation Spectroscopy (1H-1H COSY), Heteronuclear Single Quantum Coherence (HSQC), Heteronuclear Multiple-Bond Correlation (HMBC), and Nuclear Overhauser Effect Spectroscopy (NOESY). In summary, the primary structure of ZMP2 should be as follows: the main chain is connected as →4)-α-D-GalAp-(1→3)-β-D-Galp-(1→, while the end glycosidic bonds of α-D-Galp-(1→ and α-L-Araf-(1→5)-α-L-Araf-(1→ are attached to the main chain by O-3 and O-6 bonds from →3,4)-α-D-GalAp-(1→ and →3,6)-β-D-GalAp-(1→, respectively. Full article

Heterobimetallic iron–group 9 carbonyl cations, FeM(CO)_n⁺ (M = Rh, Ir; n = 9–11), were generated in the gas phase via pulsed laser vaporization within a supersonic expansion and characterized by infrared photodissociation spectroscopy in the carbonyl stretching region. By combining experimental spectra with density functional theory simulations, the geometric and electronic structures of these clusters were unambiguously assigned. Mass spectrometry and photodissociation results identified FeM(CO)₉⁺ as the saturated species for M = Rh and Ir, in contrast to the lighter cobalt analog FeCo(CO)₈⁺. The FeM(CO)₉⁺ cations adopt a C_4v-symmetric singlet ground-state structure with all carbonyl ligands terminally bound, corresponding to a (OC)₅Fe–M(CO)₄ configuration. These complexes can be formally described as combination products of the stable neutral Fe(CO)₅ and cationic M(CO)₄⁺ fragments. Analyses based on canonical molecular orbitals, Mayer bond orders, and fragment-based correlation diagrams reveal the presence of a dative Fe→M interaction in FeM(CO)₉⁺, which formally enables the heavier Rh/Ir metal center to attain an 18-electron configuration. However, this bond is weaker than a typical covalent single bond, as the key molecular orbitals involved possess antibonding character. This study provides important insights into the structure and bonding of heteronuclear transition metal carbonyl clusters, highlighting distinctive coordination behavior between late 3d and heavier 4d/5d congeners. Full article

Parahydrogen-induced hyperpolarization (PHIP), introduced nearly four decades ago, provides an elegant solution to one of the fundamental limitations of nuclear magnetic resonance (NMR)—its notoriously low sensitivity. By converting the spin order of parahydrogen into nuclear spin polarization, NMR signals can be boosted by several orders of magnitude. Here we present a portable, compact, and cost-effective setup that brings PHIP and Signal Amplification by Reversible Exchange (SABRE) experiments within easy reach, operating seamlessly across ultra-low-field (0–10 μT) and high-field (>1 T) conditions at 50% parahydrogen enrichment. The system provides precise control over bubbling pressure, temperature, and gas flow, enabling systematic studies of how these parameters shape hyperpolarization performance. Using the benchmark Chloro(1,5-cyclooctadiene)[1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene]iridium(I) (Ir–IMes) catalyst, we explore the catalyst activation time and response to parahydrogen flow and pressure. Polarization transfer experiments from hydrides to [1-¹³C]pyruvate leading to the estimation of heteronuclear J-couplings are also presented. We further demonstrate the use of Chloro(1,5-cyclooctadiene)[1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene]iridium(I) (Ir–SIPr), a recently introduced catalyst that can also be used for pyruvate hyperpolarization. The proposed design is robust, reproducible, and easy to implement in any laboratory, widening the route to explore and expand the capabilities of parahydrogen-based hyperpolarization. Full article

Diols represent a structurally diverse class of compounds with considerable biological and functional significance. Herein, we describe the synthesis of 1,1-bis(4-ethylphenyl)propan-1,2-diol (BEPP) via a Grignard reaction. The structure of BEPP was unambiguously elucidated by ¹H and ¹³C nuclear magnetic resonance (NMR), heteronuclear multiple-bond correlation (HMBC), high-resolution mass spectrometry (HRMS), and infrared (IR) spectroscopy. Full article

Antimicrobial peptides (AMPs), also referred to as host defense peptides, are promising molecules in the development of the next generation of antibiotics against drug-resistant bacterial pathogens. Thanatin comprises a family of naturally occurring cationic AMPs derived from several species of insects. The first thanatin, 21 residues long, was identified from the spined soldier bug, and more thanatin peptides have been discovered in recent studies. The 16-residue thanatin from Anasa tristis, or Ana-thanatin, represents the shortest sequence in the family. However, the antimicrobial activity and mechanistic process underpinning bacterial cell killing have yet to be reported for Ana-thanatin peptide. In this work, we examined the antibacterial activity, structures, and target interactions of Ana-thanatin. Our results demonstrated that Ana-thanatin exerts potent antibiotic activity against strains of Gram-negative and Gram-positive bacteria. Biophysical studies demonstrated that Ana-thanatin interacts with LPS outer membrane and can permeabilize the OM barrier in the process. Atomic-resolution structures of the peptide in free solution and in complex with lipopolysaccharide (LPS) micelle were solved by NMR, determining canonical β-sheet structures. Notably, in complex with LPS, the β-sheet structure of the peptide was better defined in terms of the packing of amino acid residues. Further, MD simulations demonstrated rapid binding of the Ana-thanatin peptide with the LPS molecules within the lipid bilayers. These studies have revealed structural features which could be responsible for LPS-OM disruption of the Gram-negative bacteria. In addition, NMR heteronuclear single quantum coherence (HSQC) studies have demonstrated that Ana-thanatin can strongly interact with the LPS transport periplasmic protein LptA_m, potentially inhibiting OM biogenesis. Taken together, we surmise that the Ana-thanatin peptide could serve as a template for the further development of novel antibiotics. Full article

Prostate stem cell antigen (PSCA) is a Ly6/uPAR protein that targets neuronal nicotinic acetylcholine receptors (nAChRs). It exists in membrane-tethered and soluble forms, with the latter upregulated in Alzheimer’s disease. We hypothesize that PSCA may be linked to a wider spectrum of neurological diseases and could induce neuroinflammation. Indeed, PSCA expression is significantly upregulated in the brain of patients with multiple sclerosis, Huntington’s disease, Down syndrome, bipolar disorder, and HIV-associated dementia. To investigate PSCA’s structure, pharmacology, and inflammatory function, we produced a correctly folded water-soluble recombinant analog (ws-PSCA). In primary hippocampal neurons and astrocytes, ws-PSCA differently regulates secretion of inflammatory factors and adhesion molecules and induces pro-inflammatory responses by increasing TNFβ secretion. Heteronuclear NMR and ¹⁵N relaxation measurements reveal a classical β-structural three-finger fold with conformationally disordered loops II and III. Positive charge clustering on the molecular surface suggests the functional importance of ionic interactions by these loops. Electrophysiological studies in Xenopus oocytes point on ws-PSCA inhibition of α3β2-, high-, and low-sensitive variants of α4β2- (IC₅₀ ~50, 27, and 15 μM, respectively) but not α4β4-nAChRs, suggesting targeting of the β2 subunit. Ensemble docking and molecular dynamics simulations predict PSCA binding to high-sensitive α4β2-nAChR at α4/β2 and β2/β2 interfaces. Complexes are stabilized by ionic and hydrogen bonds between PSCA’s loops II and III and the primary and complementary receptor subunits, including glycosyl groups. This study gives new structural and functional insights into PSCA’s interaction with molecular targets and provides clues to understand its role in the brain function and mental disorders. Full article