Search Results (127)

Chiral liquid chromatography (cLC) using chiral stationary phases (CSPs) has become a crucial technique for separating enantiomers. Understanding enantiomeric discrimination is essential for improving chromatographic conditions and elucidating chiral molecular recognition; the computational methods are extremely helpful for this. To assess the relevance of the association of these two approaches and to analyze the current trends, in this review, a systematic analysis of the scientific literature was performed, covering recently published works (from 2015 to January 2025) on enantioseparation by cLC using CSPs and computational studies. CSPs based on polysaccharides and Pirkle-type were the most described (accounting for 52% and 14% of the studies, respectively). Regarding the computational methods, molecular docking and molecular dynamics (MD) were the most reported (accounting for 50% and 25% of the studies, respectively). In the articles surveyed, a significant growth in research concerning both cLC enantioseparation and computational studies is evident, emphasizing the benefit of the synergy between these two approaches. Full article

The bis-thiourea chiral solvating agent (CSA) BTDA enables the NMR-based determination of absolute configuration in N-3,5-dinitrobenzoyl (DNB) amino acid derivatives without requiring covalent derivatization. A reliable trend of the sense of nonequivalence and absolute configuration is found in both ¹H and ¹³C NMR spectra. A dual-enantiomer approach, using (R,R)- and (S,S)-BTDA, generates diastereomeric complexes with the enantiopure substrate, and distinct spatial arrangements are reflected in consistent and interpretable Δδ values. The observed chemical shift differences correlate reliably with the stereochemistry of the chiral center and are further supported by ROESY (Rotating-frame Overhauser Enhancement SpectroscopY) experiments and binding constants’ measurements, confirming the formation of stereoselective non-covalent complexes. This methodology extends the logic of Mosher’s analysis to solvating agents and remains effective even in samples containing single pure enantiomers of the amino acid derivative. The BTDA-based dual-CSA system thus represents a robust, non-derivatizing strategy for stereochemical assignment by NMR, combining operational simplicity with broad applicability to DNB derivatives of amino acids with free carboxyl function. Full article

(−)-Patagonic acid (1) is a clerodane diterpene isolated from several plants from the Alismataceae, Asteraceae, Euphorbiaceae, Fabaceae, Lamiaceae, Salicaceae, Sapindaceae, and Velloziaceae families, and its biological potential as an inhibitor of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) and as an anti-inflammatory compound has been described. Furthermore, the enantiomer (+)-1 is also described in Fabaceae and Verbenaceae. A lack of formal studies about the absolute configuration (AC) determination of 1 is emphasized. Thus, the present manuscript describes the AC determination of patagonic acid (1). The chemical correlation of (−)-1 from (−)-hardwickiic acid (2) was achieved by a simplistic oxidative process. The specific rotation value and electronic circular dichroism (ECD) analysis allowed for the AC determination of (−)-1 as (5R,8R,9S,10R)-(−)-patagonic acid. ECD revealed a positive exciton chirality (EC) phenomenon in both (−)-1 and (−)-2, which is directly associated with their configuration and conformational preferences, which were assessed by DFT calculations at the B3LYP/DGDZVP level of theory. Since the NMR data of (+)-1 are fully coincident with those from its enantiomer studied herein, the chirality of (5S,8S,9R,10S)-(+)-patagonic acid could also be determined. These experimental conclusions deeply complement the literature related to clerodane compounds biosynthesized in several families of plants of scientific interest. Full article

Research at the intersection of quantum gravity and quantum information theory has seen significant success in describing the emergence of spacetime and gravity from quantum states whose entanglement entropy approximately obeys an area law. In a different direction, the Kaluza–Klein proposal aims to recover gauge symmetries by means of dimensional reduction in higher-dimensional gravitational theories. Integrating both of these, gravitational and gauge degrees of freedom in $3+1$ dimensions may be obtained upon dimensional reduction in higher-dimensional emergent gravity. To this end, we show that entangled systems of two and three qubits can be associated with $5+1$- and $9+1$-dimensional spacetimes, respectively, which are reduced to $3+1$ dimensions upon singling out a preferred complex direction. Depending on the interpretation of the residual symmetry, either the Standard Model gauge group, $SU\left(3\right)\times SU\left(2\right)\times U\left(1\right)/{\mathbb{Z}}_6$, or the symmetry of Minkowski spacetime together with the gauge symmetry of a right-handed ‘half-generation’ of fermions can be recovered. Thus, there seems to be a natural way to accommodate the chirality of the weak force in the given construction. This motivates a picture in which spacetime emerges from the area law contribution to the entanglement entropy, while gauge and matter degrees of freedom are obtained due to area-law-violating terms. Furthermore, we highlight the possibility of using this construction in quantum simulations of Standard Model fields. Full article

The development of new, more effective, and selective anticancer agents is one of the most important tasks of modern medicinal chemistry. Recently, we have found that non-classical Pd(II) pincer complexes derived from thiophosphoryl-appended picolinamides exhibit promising cytotoxic properties. In this work, the potential of this class of metal-based derivatives was studied on an extended family of Pd(II) complexes with a deprotonated amide core featuring thiophosphoryl pendant arms, readily obtained by the direct cyclopalladation of new functionalized amide ligands upon interaction with PdCl₂(NCPh)₂ under mild conditions. The ligands, in turn, were obtained by conventional amide coupling methods using (aminobenzyl)- and (aminomethyl)diphenylphosphine sulfides as the key precursors and different N- and S-donor-substituted carboxylic acids. The effect of an acid component and carbon chirality in the ligand framework on the bioactivity of the resulting Pd(II) pincer complexes was elucidated by evaluating their cytotoxicity against different solid and blood cancer cell lines, apoptosis induction ability, and P-glycoprotein (P-gp) affinity, which revealed the high anticancer potential of some of them, and in particular, the potential to overcome drug resistance associated with P-gp overexpression. The representative palladocycle was also shown to possess moderate antibacterial activity. Full article

One pair of novel enantiomers, gigantdioxin A (+)-1 and B (−)-1, with a skeleton of benzo[d][1,3]dioxin; a new acetophenone gigantone A (3); a known 3-chlorogentisyl alcohol (2), which is the bioprecursor of 1; acetophenone (4); and chromone derivative (5) were obtained from the sponge-associated fungus Aspergillus giganteus MA46-5. Their structures were established by extensive and in-depth spectral analysis, such as UV, 1D and 2D NMR, and HRESIMS. The absolute configurations of (±)-1 were deduced by ORD, chiral separation, and experimental and computational ECD. Meanwhile, we proposed a possible biosynthetic pathway of (±)-1. Fortunately, the pathway was proved by biomimetic synthesis through 2, as a bioprecursor, reacted with n-butyraldehyde. Myocardial protection assays showed that 3 and 4 possessed stronger protective effects than a positive control against myocardial cell H9c2 ischemia–reperfusion injury in low concentrations, and the effect of (−)-1 was almost equal to that of the positive control. Further, we explored the possible mechanism of myocardial protection through network pharmacology. Adenosine A2a receptor (ADORA2A) and serum albumin (ALB) represent potential targets for myocardial protection associated with (−)-1 and 4, respectively. Based on the network pharmacology, we docked the predicted proteins with bioactive compounds using Autodock Vina. Full article

We investigated Im-3m H₃S at 200 GPa, a pressure regime where crystalline H₃S is widely considered to be a superconductor. Simulated circularly polarized 10 femtosecond (fs) laser pulses were applied and we quantified the effects on the electron dynamics both during the application of the ultra-fast laser pulse and 5.0 fs after the pulse was switched off. In addition, the carrier-envelope phase (CEP) angle ϕ, which quantifies the relationship between the time-varying direction of electric (E)-field and the amplitude envelope, is employed to control the time evolution of the wavefunction ψ(r). This is undertaken for the first application of Next Generation Quantum Theory of Atoms in Molecules (NG-QTAIM) to the solid state. Ultra-fast phenomena related to superconductivity are discovered in the form of a geometric Berry phase angle associated with the H--H bonding in addition to very high values of the chirality–helicity function that correspond to values normally found in chiral molecules. Future applications are discussed, including chiral spin selective phenomena in addition to high-temperature superconductivity and organic superconductors where phonons do not play a significant role. Full article

Osteoporosis, a chronic bone disorder, poses a global threat to the health of millions of individuals. The disruption of bone homeostasis is the fundamental cause of osteoporosis. Currently, clinical drugs are employed to promote bone formation via enhancing osteogenesis and/or reduce bone loss via inhibiting osteoclastogenesis. However, it is difficult for the current drugs to simultaneously address the osteoblastogenesis and osteoclastogenesis issues associated with osteoporosis. Hence, L/D-phenylalanine derivatives (L/DPF), combined with Mg²⁺ ions, are employed to assemble into chiral supramolecular hydrogels which facilitate osteocyte activity and inhibit osteoclast function. LPF_Mg hydrogels and DPF_Mg hydrogels demonstrate the opposite supramolecular chirality. Specifically, LPF_Mg hydrogels and DPF_Mg hydrogels are composed of left-handed (M-type) helical nanofibers and right-handed (P-type) helical nanofibers, respectively. The hydrogen bonding and π–π stacking interactions are crucial in the process of hydrogel formation. The chiral left-handed nanofibrous DPF_Mg hydrogels significantly promote osteogenic differentiation of MC3T3 cells and inhibit osteoclast differentiation of RAW267.4 cells, thereby demonstrating substantial potential for applications in improving skeletal health. These findings provide a promising novel perspective on the application of chiral functional materials for osteoporosis therapy. Full article

The present study focused on the mesonic potential contributions to the Lagrangian of the extended linear sigma model (eLSM) for scalar and pseudoscalar meson fields across various quark flavors. The present study focused on the low-energy phenomenology associated with quantum chromodynamics (QCD), where mesons and their interactions serve as the pertinent degrees of freedom, rather than the fundamental constituents of quarks and gluons. Given that SU(4) configurations are completely based on SU(3) configurations, the possible relationships between meson states in SU(3) and those in SU(4) were explored at finite temperature. Meson states, which are defined by distinct chiral properties, were grouped according to their orbital angular momentum J, parity P, and charge conjugation C. Consequently, this organization yielded scalar mesons with quantum numbers $J^{PC}=0^{++}$, pseudoscalar mesons with $J^{PC}=0^{-+}$, vector mesons with $J^{PC}=1^{--}$, and axial vector mesons with $J^{PC}=1^{++}$. We accomplished the derivation of analytical expressions for a total of seventeen noncharmed meson states and twenty-nine charmed meson states so that an analytical comparison of the noncharmed and charmed meson states at different temperatures became feasible and the SU(3) and SU(4) configurations could be analytically estimated. Full article

Human lactate dehydrogenase A (hLDHA) is a homotetrameric isozyme involved in the conversion of glyoxylate into oxalate in the cytosol of liver cells (hepatocytes) and partially responsible for the overproduction of oxalate in patients with the rare disease called primary hyperoxaluria (PH). Recently, hLDHA inhibition has been validated as a safe therapeutic method to try to control the PH disease. Stiripentol (STP) is an approved drug used in the treatment of seizures associated with Dravet’s syndrome (a severe form of epilepsy in infancy) which, in addition, has been drawing interest in recent years also for potentially treating PH, due to its hLDHA inhibitory activity. In this work, several new STP-related compounds have been synthesized and their hLDHA inhibitory activity has been compared to that of STP. The synthesis of these analogues to STP was accomplished using crossed-aldol condensation guided by lithium enolate chemistry and a successive regioselective reduction of the resulting α,β-unsaturated ketones. The target molecules were obtained as racemates, which were separated into their enantiomers by chiral HPLC. The absolute configurations of pure enantiomers were determined by the modified Mosher’s method and electronic circular dichroism (ECD) spectroscopy. For the inhibitory effect over the hLDHA catalytic activity, a kinetic spectrofluorometric assay was used. All the new synthesized compounds turned out to be more active at 500 μM (46–72% of inhibition percentage) than STP (10%), which opens a new line of study on the possible capacity of these analogues to reduce urinary oxalate levels in vivo more efficiently. Full article

Recently, two new polymorphs have been added to the nematic class: the polar-twisted nematic (N_PT) in 2016 and the ferroelectric nematic (N_F) in 2020. Comprised of achiral molecules, both exhibit local polar ordering and adopt modulated structures, right- and left-handed helical organizations—form chirality—albeit on vastly different dimensional scales; modulations have a ~10 nanometer pitch in the N_PT and ~500 nm in the N_F. Here, we focus on the structure and symmetries of the N_PT phase and the ensuing physical properties. Based on an array of order parameters that fully describe the molecular ordering and the nano-modulations thereof, we present a consistent formulation of the dielectric, optical, surface anchoring, and elasticity properties of the N_PT materials. We show that these properties are distinctly different from those associated with an elastically modulated, locally uniaxial, nematic. Full article

Five chiral, racemic dialkyl α-hydroxyethylphosphonates and α-hydroxyethyl-diarylphosphine oxides were prepared in a scalable manner. Possibilities for the optical resolution of the racemic hydroxyphosphine oxides were explored via diastereomeric complex-forming experiments. The acidic calcium salt of O,O′-dibenzoyl-(2R,3R)-tartaric acid and O,O′-di-p-tolyl-(2R,3R)-tartaric acid were chosen as the resolving agents. The role of the solvent in the enantiomeric discrimination was investigated. The diastereomeric complex could be obtained in a crystalline form for α-hydroxyethyl-diphenylphosphine oxide and α-hydroxyethyl-bis(4-methylphenyl)phosphine oxide. However, in the third case, for α-hydroxyethyl-bis(3,5-dimethylphenyl)phosphine oxide, there was no chiral discrimination. Decomposition of the recrystallized diastereomeric complex followed by decomposition of the complex yielded the target compounds in 77/90% enantiomeric excess. The absolute configuration of the hydroxyethyl-diphenylphosphine oxide was determined by single-crystal X-ray diffraction measurements. The interactions stabilizing the supramolecular associate were evaluated. Full article

Biofilm-associated microbes are 10–1000 times less susceptible to antibiotics. An emerging treatment strategy is to target the structural components of biofilm to weaken the extracellular matrix without introducing selective pressure. Biofilm-associated bacteria, including Escherichia coli and Staphylococcus aureus, generate amyloid fibrils to reinforce their extracellular matrix. Previously, de novo synthetic α-sheet peptides designed in silico were shown to inhibit amyloid formation in multiple bacterial species, leading to the destabilization of their biofilms. Here, we investigated the impact of inhibiting amyloid formation on antibiotic susceptibility. We hypothesized that combined administration of antibiotics and α-sheet peptides would destabilize biofilm formation and increase antibiotic susceptibility. Two α-sheet peptides, AP90 and AP401, with the same sequence but inverse chirality at every amino acid were tested: AP90 is L-amino acid dominant while AP401 is D-amino acid dominant. For E. coli, both peptides increased antibiotic susceptibility and decreased the biofilm colony forming units when administered with five different antibiotics, and AP401 caused a greater increase in all cases. For S. aureus, increased biofilm antibiotic susceptibility was also observed for both peptides, but AP90 outperformed AP401. A comparison of the peptide effects demonstrates how chirality influences biofilm targeting of gram-negative E. coli and gram-positive S. aureus. The observed increase in antibiotic susceptibility highlights the role amyloid fibrils play in the reduced susceptibility of bacterial biofilms to specific antibiotics. Thus, the co-administration of α-sheet peptides and existing antibiotics represents a promising strategy for the treatment of biofilm infections. Full article

For radially extended Bessel modes, the helicity density distributions of magnetic fields associated with relativistic electron vortex beams are investigated for first time in the literature. The form of the distribution is defined by the electron beam’s cylindrically symmetric density flux, which varies with the winding number ℓ and the electron spin. Different helicity distributions are obtained for different signs of the winding number $\pm \ell$, confirming the chiral nature of the magnetic fields associated with the electron vortex beam. The total current helicity for the spin-down state is smaller than that of the spin-up state. The different fields and helicities associated with opposite winding numbers and/or spin values will play an important role in the investigation of the interaction of relativistic electron vortices with matter and especially chiral matter. A comparison of the calculated quantities with the corresponding ones in the case of non-relativistic spin-polarized electron beams is performed. Full article

Isatropolone C from Streptomyces sp. CPCC 204095 features a fused cyclopentadienone-tropolone-oxacyclohexadiene tricyclic moiety in its structure. Herein, we report an isatropolone C dimer derivative, di-isatropolone C, formed spontaneously from isatropolone C in methanol. Notably, the structure of di-isatropolone C resolved by NMR reveals a newly formed cyclopentane ring to associate the two isatropolone C monomers. The configurations of four chiral carbons, including a ketal one, in the cyclopentane ring are assigned using quantum NMR calculations and DP4+ probability. The plausible molecular mechanism for di-isatropolone C formation is proposed, in which complex dehydrogenative C-C bond coupling may have happened to connect the two isatropolone C monomers. Like isatropolone C, di-isatropolone C shows the biological activity of inducing autophagy in HepG2 cells. Full article