Search Results (1,396)

To investigate the potential of halogen-containing building blocks in the development of artificial carbohydrate receptors, the 1,3,5-trisubstituted 2,4,6-triethylbenzene scaffold with halogenated subunits and classical hydrogen bonding sites was used as a model system. In the first studies, the influence of the presence of halogens on the binding properties of compounds bearing benzamidomethyl units was investigated, whereby the type of halogen and its ring position were varied. The question was whether the presence of halogens could lead to an increase in binding effectivity and whether this increase can be attributed to the formation of halogen bonds (especially for X = Br and I in ortho position) with the sugar substrate or to other effects. The binding studies revealed some interesting relationships between structure and binding affinity for the tested compounds 1–9. For those bearing the halogen substituent in the ortho position to the amide functionality, the binding affinity increases in the expected order 4 (o-F) < 3 (o-Cl) < 2 (o-Br) < 1 (o-I). In the presence of small amounts of water in CDCl₃, an increase in binding strength was observed in comparison to experiments conducted in dry CDCl₃. The present studies aim to provide impulses for the use of halogenated building blocks in the design of artificial carbohydrate receptors. Optimizing the type of halogenated units and the receptor architecture should result in more effective carbohydrate receptors capable of functioning effectively in aqueous media through a combination of different noncovalent interactions. Full article

Seminaphtofluorones (SNAFRs) are a family of benzannulated xanthene dyes that exhibit strong fluorescence in both neutral and anionic states and can reach emission wavelengths in the deep-red to near-infrared region. Their optical response is highly sensitive to regioisomerism and functionalization, making them attractive candidates for systematic structure–property investigations. Here, we computed the photophysical properties of six SNAFR regioisomers for both neutral and anionic species and correlate the calculated results with available experimental data. From the six dyes, we further chose two of them, SNAFR4 and SNAFR6, to further investigate how phenyl-ring functionalization modulates SNAFR properties by introducing methyl (–CH₃) and carboxyl (–COOH) substituents at the ortho (o), meta (m), and para (p) positions. The calculations indicate that substitution induces measurable changes in geometries, as well as in excitation and emission energies, with particularly pronounced effects for the anionic derivatives. Overall, these results provide a computational framework for the rational tuning of SNAFRs’ optical properties and the design of derivatives with tailored optical characteristics for fluorescence imaging and applications in photodynamic therapy. Full article

Phenetole derivatives with dual ethoxy substituents exhibit rich conformational diversity and complex vibronic characteristics, making them important model compounds for understanding substituent effects on molecular structure and spectroscopy. In this work, we systematically investigated the stable rotamers, vibronic spectra, and cationic ground-state features of p-diethoxybenzene (PDEB) using resonance-enhanced multiphoton ionization (REMPI), UV-UV hole-burning (HB), and mass-analyzed threshold ionization (MATI) spectroscopies, combined with density functional theory (DFT) calculations. The ground-state potential energy surface (PES) of PDEB was calculated at the B3LYP/6-311++G(d,p) level, identifying eight rotamers with distinct statistical weights and relative energies. Hole-burning spectroscopy resolved two dominant rotamers (cis/up–up and trans/up–down) in the supersonic molecular beam, with their S₁←S₀ transition origins determined as 33,824 cm⁻¹ and 33,613 cm⁻¹, respectively. Franck-Condon simulations of the vibronic transitions showed excellent agreement with the experimental REMPI spectra, enabling precise assignment of substituent and benzene ring vibrational modes. MATI experiments yielded accurate adiabatic ionization energies (AIEs) of the cis and trans rotamers as 59,629 ± 5 cm⁻¹ and 59,432 ± 5 cm⁻¹, respectively, and identified active cationic vibrational modes in the D₀ state. Geometric parameters of PDEB in the S₀, S₁, and D₀ states were calculated at the B3PW91/aug-cc-pVTZ, TD-B3PW91/aug-cc-pVTZ, and UB3PW91/aug-cc-pVTZ levels, revealing structural evolution during electronic excitation and ionization. The effects of ethoxy substituent orientation on molecular energy, vibrational frequencies, and ionization energy are discussed, and differences in spectral characteristics between PDEB and its meta isomer (MDEB) are compared. This work provides a comprehensive spectral and structural database for p-diethoxybenzene and deepens the understanding of structure–property relationships in diethoxybenzene isomers. Full article

Electronics evolution drives SMMs as a frontier, overcoming conventional magnetic material limits via molecular spin coupling. Two relevant Co(II) mononuclear complexes, [Co(MOP)₄(N₃)₂] (1) and [Co(MSP)₄(N₃)₂] (2) (MOP = 4-methoxypridine and MSP = 4-methylthiopyridine) were synthesized through changing the substituents of ligands. The Co(II) ions in the two complexes show octahedron coordination geometries. The replacement of the O to S in the equatorial plane leads to different Jahn–Teller effect because of the shorter Co(II)-N in the equatorial plane, resulting in the significantly different slow relaxation process confirmed by ab initio calculation. The results confirm the Co(II) ion is sensitive to ligand field. Full article

Ruthenocene (Rc) and its derivatives form a structurally versatile class of metallocenes with unique and multifunctional applicability. This review presents a detailed analysis of Rc chemistry including the structural comparison with ferrocene, its redox behavior, and substituent effects. We also discuss its applications in sensing, energy storage, photochemistry, and biomedicine. Rc exhibits unique conformational and adaptive electronic properties based on one and two-electron oxidation processes. Electrochemical investigations of Rc to date indicate that its redox behavior is strongly dependent on the electrolyte system, exhibiting quasi-Nernstian characteristics, the formation of stabilized dimeric species [Rc₂]²⁺, and interconversion among Ru(II), Ru(III), and Ru(IV) oxidation states. Rc-based systems exhibit superior performance as redox mediators and labels in electrochemical sensing systems in terms of electron-transfer kinetics, signal amplification, and surface immobilization. In the field of energy storage, Rc decreases the charging overpotential and increases the cycle life of Li-O₂ batteries. Rc further acts as a photoinitiator via charge-transfer-to-solvent and efficient photoinduced electron transfer in metalloporphyrin and fullerene dyads. In biomedical research, Rc derivatives as well as bioconjugates possess promising anticancer activities, displaying reactive oxygen species generation, topoisomerase inhibition, thioredoxin reductase inhibition, receptor-mediated uptake, and target peptide conjugation. Given its flexible ligand design, electrolyte driven redox behaviors, and antiproliferative properties, Rc exhibits a very adaptive molecular scaffold for next generation electrochemical technologies as well as metallodrug design. Full article

Zinc and iron are essential micronutrients in crop nutrition, and polymer-based nanogels have emerged as promising carriers to modulate their availability in sustainable agricultural systems. Here, a polymeric model receptor was designed to investigate how the nature and position of electron-donating (–NH₂) and electron-withdrawing (–NO₂) substituents control the recognition of Zn²⁺ and Fe²⁺ cations. Using a combination of density functional theory calculations, energy decomposition analysis with natural orbitals for chemical valence (EDA–NOCV), electrostatic potential (ESP) mapping, and quantum theory of atoms in molecules (QTAIM) method, the receptor–cation interactions are dissected into electrostatic, Pauli repulsion, orbital, and dispersion contributions. The results show that complex stability is governed mainly by orbital and electrostatic terms, with Fe²⁺ forming the most stable complex (−393.57 kcal mol⁻¹) with regard to a Zn²⁺ similar complex (−288.80 kcal mol⁻¹). Zn²⁺ complexes exhibit a broad tunability with substituent pattern. Electron-donating groups systematically strengthen both electrostatic and orbital components, whereas nitro substituents display a pronounced positional effect, ranging from strong destabilization to significant stabilization of Zn²⁺ binding. These findings establish molecular-level guidelines for engineering polymeric nanogels with tunable affinity and selectivity toward micronutrient cations in agricultural applications. Full article

This study aims to systematically investigate the influence of substituent effects on the strength of Lewis acid–base interactions in frustrated Lewis pairs (FLPs). Specifically, -C₆F₅ groups of the classical Lewis acid B(C₆F₅)₃ are sequentially replaced with -C₆Cl₅, -C₆Br₅, and -C₆I₅ groups, and the Lewis acids are paired with the Lewis base 1,3-disubstituted imidazol-2-ylidene (ItBu) to form FLPs. Further energy decomposition analysis (sobEDA), orbital analysis, and molecular fragment density difference (MFDD) analysis reveal the nature of the substituent effect on the interaction energy (∆Eint) of the FLPs. The research findings indicate that the ∆Eint of B(C₆F₅)3-ItBu, B(C₆F₅)_x(C₆Y₅)_3−x-ItBu (x = 0, 1, 2; Y = Cl, Br, I) originates mainly from the interaction between the outermost halogen atom of the Lewis acid and the central carbon (C) atom of the Lewis base, rather than from the interaction between the central atoms boron (B) and carbon (C). This mechanism ultimately leads to a ∆Eint for B(C₆F₅)₂(C₆Y₅)-ItBu (Y = Cl, Br, I) that is comparable to that of B(C₆F₅)₃-ItBu. This indicates that modified B(C₆F₅)₂(C₆Y₅) (Y = Cl, Br, I) exhibits greater potential for the construction of novel FLPs. Full article

Non-metallic hydride donors have emerged as an interesting, highly tunable class of compounds capable of CO₂ reduction, with benzimidazoles being simple, yet efficient and regenerable, representatives. In this work, the role of superbases as auxiliary groups attached to the benzimidazole framework was investigated using the CPCM(CH₃CN)/ωB97xD/aug-cc-pVTZ//CPCM(CH₃CN)/ωB97xD/6-31+G(d,p) approach. Three modes of operation were assessed through hydricity calculations and the modeling of two different CO₂ reduction mechanisms. Among the superbases considered, phosphazene substituents yielded the largest increase in the hydride donation ability, lowering hydricity by 6 kcal mol⁻¹ relative to 2-methylbenzimidazole, with the α-substitution exerting a stronger effect than β-substitution. For most systems, changes in hydricity correlate with changes in aromaticity, except in systems where steric congestion limits optimal substituent alignment. CO₂ activation pathways encompassing guanidine/CO₂ hydrogen bonding and guanidinium carboxamidine formation were modeled. In the former, transition state structures were significantly stabilized, and the overall exergonicity of the reduction is enhanced. Also, utilizing the longer and more flexible linker additionally decreases the barrier for the reaction. The carboxamidine pathway is disfavored because of the high stability of the carboxamidine intermediate and low barrier for the C–N bond cleavage, which reverses the mechanism to the reduction of isolated CO₂. Full article

Amphiphilic cationic lipids based on the 1,4-dihydropyridine (1,4-DHP) scaffold represent a versatile platform for the development of self-assembling delivery systems. In this work, a series of ten new amphiphilic 1,4-DHP derivatives bearing branched ester substituents at the 3,5-positions and quaternized cationic groups at the 2,6-positions were designed and synthesized. The effect of branched ester chain length and branching on nanoparticle formation was investigated. The self-assembling properties of the synthesized amphiphiles were evaluated by dynamic light scattering using an ethanol injection method. All compounds formed positively charged nanoparticles with hydrodynamic diameters ranging from 52 to 439 nm and polydispersity index from 0.194 to 0.452. Amphiphiles 14b–17b with 2-hexyldecyl substituents formed smaller particles, with an average diameter below 100 nm. Several derivatives exhibited good stability over a 14-day storage period at room temperature. To clarify structure–property relationships, lipophilicity (AlogP), polar surface area (PSA), and pK_a values were calculated using Schrödinger computational tools. The compounds displayed high lipophilicity AlogP 8.98–19.32, while PSA values remained within a narrow range. The calculated pK_a values ranged from 7.20 to 10.99. The results demonstrate that both the length and architecture of branched ester chains significantly influence nanoparticle size, homogeneity, and stability, highlighting branched-chain 1,4-DHP amphiphiles as promising synthetic lipid candidates for further development of delivery systems after evaluation of biological properties. Full article

This study presents a quantitative investigation of substituent effects on the stability of 1:2 complexes formed between para-substituted 2-phenylbenzimidazole ligands and Cu(II) or Co(II) ions. The ligands, featuring hydroxyl (–OH), chloro (–Cl), and nitro (–NO₂) substituents, were synthesized via copper acetate-mediated oxidative cyclization. Stability constants (log K) were determined spectrophotometrically using both the Benesi–Hildebrand and Job methods, which yielded perfectly consistent results and confirmed ML₂ stoichiometry. For both metal series, the stability decreases in the order –OH > –Cl > –NO₂. Excellent linear correlations were obtained between log K and Hammett σ constants, yielding reaction constants of ρ = −0.79 for Cu(II) and ρ = −1.00 for Co(II). These negative ρ values confirm that electron-donating substituents enhance complex stability by increasing electron density on the donor nitrogen. Furthermore, the stability constants for Cu(II) complexes are approximately two orders of magnitude higher than those for Co(II), in agreement with the Irving–Williams series. This work establishes a clear, predictive structure–stability relationship and validates the combined methodological approach for quantifying metal–ligand interactions in tunable benzimidazole systems. Full article

The discovery of novel anti-infective agents is a continuous challenge in medicinal chemistry, particularly due to the rise in resistant fungal and viral strains. Within this context, the biphenyl subunit has been identified as a highly versatile privileged structure capable of interacting with diverse protein targets via hydrophobic and π-interactions. The purpose of this study is to review the pharmacological potential of biphenyl-based compounds, focusing on their application as anti-infective agents. We comprehensively analyzed recent literature and rational design strategies concerning biphenyl derivatives, examining structure-activity relationships, molecular docking insights, and structural optimizations aimed at enhancing both pharmacodynamics and pharmacokinetics. The reviewed studies demonstrate that incorporating biphenyl moieties yields compounds with potent antifungal and antiviral activities. Specifically, optimized biphenyl derivatives exhibit strong inhibitory effects against resistant Candida strains and crucial viral targets, including mutant variants of the HIV-1 reverse transcriptase and protease enzymes. Furthermore, strategic modifications, such as scaffold hopping and the introduction of specific substituents, successfully mitigated cytotoxicity and improved metabolic stability against cytochrome P450 enzymes. Biphenyl serves as a robust and adaptable scaffold for drug design. Its rational structural optimization provides a viable pathway to overcome drug resistance and develop effective, metabolically stable anti-infective therapeutics. Full article

In order to find green fungicides derived from natural products, 22 unreported anethole-based thiazolinone-hydrazone compounds were designed and synthesized, and their structures were characterized by FT-IR, ¹H NMR, ¹³C NMR, and HRMS. At a concentration of 50 mg/L, the preliminary antifungal activity of the target compounds against eight plant pathogens was evaluated. The results showed that 5q (R = m-OH C₆H₄) exhibited the best inhibitory activity against most of the tested plant pathogenic fungi, demonstrating that this compound had certain broad-spectrum antifungal activity. In addition, a reasonable and effective 3D-QSAR model (r² = 0.994, q² = 0.529) was established using the comparative molecular field analysis (CoMFA) method to study the relationship between the structures of the target compounds and their antifungal activity against Physalospora piricola. Meanwhile, the results of electrostatic potential calculation of the compounds indicated that the electronic effect caused by different substituents on the benzene ring might be one of the factors affecting antifungal activity. In addition, frontier molecular orbital calculations implied that the anethole moiety and the thiazolinone-hydrazone-benzene structure in the target compounds might play an important role in antifungal activity. The potential binding mode between the target compound 5q (R = m-OH C₆H₄) and the homology-modeled succinic dehydrogenase was explored by molecular docking. Full article

The fluorescence properties of organic molecules are largely determined by molecular architecture, π-conjugation, and electronic substituent effects. In this study, three novel pyrene-chromone Schiff base derivatives were designed and synthesized to investigate substituent-driven modulation of photophysical behavior. The compounds were obtained via condensation of 1-aminopyrene with three different chromone-based aldehydes and fully characterized by FT-IR, ¹H-NMR, and mass spectrometry. The molecular design involves a donor-π-acceptor architecture: pyrene donates electrons, while the chromene moiety accepts them, enabling charge transfer upon excitation. UV-Vis and fluorescence spectroscopy revealed intense absorption in the 430–440 nm range and tunable emission in the 540–565 nm region, corresponding to large Stokes shifts (107–125 nm). Substituent effects significantly influenced optical band gaps and emission intensities, with the nitro-substituted derivative exhibiting a reduced band gap and pronounced fluorescence quenching due to enhanced intramolecular charge transfer. Concentration-dependent absorption studies demonstrated linear Beer–Lambert behavior, indicating the absence of aggregation within the investigated range. These results establish clear structure–property relationships in pyrene-chromene Schiff bases and highlight their potential as promising candidates for optoelectronic and fluorescence-based sensing applications. Full article

Background/Objectives: The emergence of antimicrobial resistance necessitates the development of new and effective antimicrobial agents. In this study, three different series of imidazole-based chalcones (IBC1-25) were designed and synthesised using a sustainable approach, with the aim of identifying compounds with enhanced antimicrobial activity. Methods: A series of monoalkoxy, dialkoxy, and trialkoxy imidazole-based chalcones (IBC1–25) were synthesised and evaluated for their antimicrobial and antifungal activities against a range of microbial strains. Structure-activity relationships were analysed, and molecular docking studies were performed to investigate potential binding interactions with biofilm-associated regulatory proteins. In addition, ADME properties were predicted to assess drug-likeness. Results: Among the monoalkoxy derivatives (IBC1-14), IBC5 exhibited the broadest spectrum of activity, particularly against S. epidermidis. Several dialkoxy analogues (IBC17-21) demonstrated improved potency, with IBC20 showing notably high activity. While IBC22 and IBC25 were largely ineffective, IBC23 and IBC24 displayed significant antibacterial and antifungal activities. Overall, dialkoxy and trialkoxy derivatives exhibited enhanced efficacy, whereas monoalkoxy compounds with bulky or long-chain substituents were generally less active. The presence of multiple alkoxy substituents, such as methoxy and ethoxy groups, on the phenyl ring significantly improved activity, particularly against fungi and Gram-positive bacteria. Molecular docking studies revealed that IBC20 and IBC23 showed favourable binding to the biofilm-associated regulator TcaR, suggesting a potential allosteric inhibition mechanism, while weak interactions were observed with TagF. ADME predictions indicated good oral absorption and compliance with key drug-likeness criteria. Conclusions: The results demonstrate that both the number and type of alkoxy substituents play a critical role in antimicrobial activity. In particular, IBC20 and IBC23 emerge as promising candidates for further development as antimicrobial agents targeting biofilm-associated pathways. Full article

We report the synthesis, spectroscopic characterization, and single-crystal X-ray structures of 5-methyl-3-phenylbenzo[e][1,2,4]triazine (I) and its precursor N′-(3-methyl-2-nitrophenyl)benzohydrazide (IV). Compound IV was obtained by nucleophilic aromatic substitution of 1-fluoro-3-methyl-2-nitrobenzene with benzohydrazide and was converted to I through a reductive cyclodehydration/oxidative aromatization sequence. The present study provides a concise route to the 5-methyl regioisomer together with full structural characterization and examines how methyl substitution at the 5-position influences molecular geometry and crystal packing relative to the previously reported 6- and 8-methyl analogs. X-ray analysis shows that IV adopts a conjugated hydrazide framework with a twisted N–N linkage and an out-of-plane nitro group. In the crystal, it forms one-dimensional N–H⋯O hydrogen-bonded chains further assembled by weaker intermolecular contacts. By contrast, I displays an essentially planar benzo[e][1,2,4]triazine core with an almost coplanar phenyl substituent and packs into slipped π-stacked columns reinforced by secondary C–H⋯N contacts. Comparison with the previously reported methyl regioisomers shows that relocation of the methyl group to the 5-position has little effect on the intrinsic molecular geometry of the benzo[e][1,2,4]triazine scaffold, while subtly modulating the stacking arrangement and secondary packing interactions in the solid state. These results further define the role of methyl-substituent position in shaping the supramolecular organization of 3-phenylbenzo[e][1,2,4]triazines. Full article