Structural Modifications Research Articles

Scaled and Weighted Laplacian Matrices as Functional Descriptors for GPCR Ligands.

The G protein-coupled receptor (GPCR) pharmacology accounts for a significant field in research, clinical studies, and therapeutics. Computer-aided drug discovery is an evolving suite of techniques and methodologies that facilitate accelerated progress in drug discovery and repositioning. However, the structure-activity relationships of molecules targeting GPCRs are highly challenging in many cases since slight structural modifications can lead to drastic changes in biological functionality. Numerous molecular descriptors have been described, many of which successfully characterize the structural and physicochemical features of drug sets. Nonetheless, elucidating the structure-functionality relationships over extensive sets of drugs with multiple structural variations and known biological activity remains challenging in various biological systems. This work presents novel topological descriptors using Laplacian matrices, weighted, and scaled by atomic mass and partial charges. We tested these descriptors on three sets of GPCR ligands: muscarinic, β-adrenergic, and δ-opioid receptor ligands, evaluating their potential as functional descriptors of these receptors.

Design a functional graphene with decoration of dual transition metal dopants for hydrogen evolution electrocatalysis.

Since hydrogen is a promising alternative to fossil fuels due to its high energy density and environmental friendliness, water electrolysis for hydrogen production has received widespread attentions wherein the development of active and stable catalytic materials is a key research direction. This article designs a dual transition metal doped functional graphene for hydrogen evolution reaction via density functional theory calculations. Among varied combinations, 16 candidates are screened out that are expected to be stable as reflected by the criterion of formation energy Ef < 0 and active due to its free energy of hydrogen adsorption ∆GH within the window of ±0.3 eV. Considering its feasibility in structural modification and electronic adjustment due to the strong dd orbital couplings, the homogeneous dual-atom moiety delivers improved performance toward hydrogen evolution in comparison with the single-atom counterpart. Owing to the good resistance of electrochemical dissolution, the work figures out the potential combinations of Cu2C3N3, Rh2C6, Rh2C3N3 and Rh2N6 endowed with the ∆GH values of -0.03, 0.12, -0.21, and 0.06 eV, respectively, being comparable to the benchmark Pt materials. Therefore, this study provides a new direction for the experimental synthesis of highly active carbon-based electrocatalysts and highlights the well-tuning ability posed by dual-atom interaction.

Synaptic cleft geometry modulates NMDAR opening probability by tuning neurotransmitter residence time.

Synaptic morphology plays a critical role in modulating the dynamics of neurotransmitter diffusion and receptor activation in interneuron communication. Central physical aspects of synaptic geometry, such as the curvature of the synaptic cleft, the distance between the presynaptic and postsynaptic membranes, and the surface area-to-volume ratio of the cleft, crucially influence glutamate diffusion and N-Methyl-D-Aspartate receptor (NMDAR) opening probabilities. In this study, we developed a stochastic model for receptor activation using realistic synaptic geometries. Our simulations revealed substantial variability in NMDAR activation, showing the significant impact of synaptic structure on receptor activation. Next, we designed a theoretical study with idealized cleft geometries to understand the impact of different biophysical properties on receptor activation. Specifically, we found that increasing the curvature of the synaptic membranes could compensate for reduced NMDAR activation when the synaptic cleft width was large. Additionally, non-parallel membrane configurations, such as convex presynapses or concave postsynaptic densities (PSDs), maximize NMDAR activation by increasing the surface area-to-volume ratio, thereby increasing glutamate residence time and reducing glutamate escape. Furthermore, clustering NMDARs within the PSD significantly increased receptor activation across different geometric conditions and mitigated the effects of synaptic morphology on NMDAR opening probabilities. These findings highlight the complex interplay between synaptic geometry and receptor dynamics and provide important insights into how structural modifications can influence synaptic efficacy and plasticity. By considering the major physical factors that affect neurotransmitter diffusion and receptor activation, our work offers a comprehensive understanding of how variations in synaptic geometry regulate neurotransmission.

Effect of Fe doping on structural, optical and magnetic properties of CdS quantum dots

Abstract Pure CdS nanoparticles and Fe-doped CdS quantum dots (Cd₁₋ₓFeₓS, where x = 0.0, 0.03, 0.06, 0.09, and 0.12) were successfully synthesized using the co-precipitation method. X-ray diffraction (XRD) analysis confirmed the cubic phase structure of CdS without additional peaks, indicating the effective incorporation of Fe ions into the CdS lattice. The crystallite size exhibited a gradual increase with increasing Fe content. High-resolution transmission electron microscopy (HR-TEM) revealed a well-defined spherical morphology for pure CdS, while Fe doping induced notable agglomeration in the quantum dots. X-ray photoelectron spectroscopy (XPS) confirmed the formation of the CdFeS composition and provided insights into the valence states of Cd, Fe, and S. UV-Vis diffuse reflectance spectroscopy (DRS) demonstrated a decrease in the optical band gap from 2.29 eV to 2.18 eV with Fe doping, indicating a modification of the electronic structure. Magnetization studies revealed a transition from diamagnetic behavior in pure CdS to ferromagnetic behavior in Fe-doped samples. Additionally, Fe doping significantly influenced the magnetic parameters, including saturation magnetization, remanence, and coercivity. These results highlight the structural, optical, and magnetic properties of CdS can be tuned through Fe doping, making these materials promising candidates for optoelectronic and spintronic applications.&amp;#xD;Keywords: CdS quantum dots, XRD, XPS, optical energy gap, ferromagnetism.&amp;#xD;

Synthesis and Application of 4′-C-[(N-alkyl)aminoethyl]thymidine Analogs for Optimizing Oligonucleotide Properties

Gapmer-type antisense oligonucleotides (ASOs) are an emerging class of therapeutic agents that directly inhibit pathogenic mRNA. In this study, three new 4′-C-substituted thymidine analogs were generated using a synthetic strategy recently established by our group, namely, 4′-C-(N-ethyl) aminoethyl (4′-EAE-T), 4′-C-(N-butyl) aminoethyl (4′-BAE-T), and 4′-C-(N-octyl) aminoethyl (4′-OAE-T). Their properties were evaluated and compared with those of previously reported analogs, including 4′-C-aminoethyl (4′-AE-T) and 4′-C-(N-methyl) aminoethyl (4′-MAE-T). The novel nucleoside analogs were subsequently incorporated into gapmer-type ASOs featuring phosphorothioate (PS) linkages and locked nucleic acids (LNAs) in the wing regions. The incorporation of 4′-EAE-T and 4′-BAE-T analogs resulted in RNA binding affinities similar to that of the previously reported 4′-MAE-T analog, whereas a marked decrease in RNA affinity was noted for 4′-OAE-T, however, this reduction was mitigated when combined with other chemical modifications. Furthermore, the structural modifications conferred enhanced nuclease resistance under bovine serum conditions, with 4′-EAE-T resulting in the highest stability, followed by 4′-BAE-T and 4′-OAE-T. Additionally, oligonucleotides modified with the developed analogs preserved their RNase H cleavage susceptibility, albeit inducing minor alterations in the cleavage pattern. Finally, the oligonucleotides were applied in a gene silencing experiment targeting the KRAS gene, conducted without the use of transfection agents, displaying gene silencing activities comparable to that of the control, with the exception of the 4′-OAE-modified nucleotide, which exhibited low activity.

Review: Overview of Organic Cathode Materials in Lithium-Ion Batteries and Supercapacitors

Organic materials have emerged as promising candidates for cathode materials in lithium-ion batteries and supercapacitors, offering unique properties and advantages over traditional inorganic counterparts. This review investigates the use of organic compounds as cathode materials in energy storage devices, focusing on their application in lithium-ion batteries and supercapacitors. The review covers various types of organic materials, organosulfur compounds, organic free radical compounds, organic carbonyl compounds, conducting polymers, and imine compounds. The advantages, challenges, and ongoing developments in this area are examined and the potential of organic cathode materials to achieve higher energy density, improved cycling stability, and environmental sustainability is highlighted. The comprehensive analysis of organic cathode materials provides insights into their electrochemical performance, electrode reaction mechanisms, and design strategies such as molecular structure modification, hybridization with inorganic components, porous architectures, conductive additives, electrolyte optimization, binder selection, and electrode architecture to improve their efficiency and performance. In addition, future research in the field of organic cathode materials should focus on addressing current limitations such as low energy density, cycling stability, poor discharge capability, potential safety concerns and improving their performance. To do this, it will be necessary to improve structural stability, conductivity, cycle life, and capacity fading, explore new redox-active organic compounds, and pave the way for the next generation of high-performance energy storage devices. For organic cathode materials to be commercially viable, it is also essential to develop scalable and economical manufacturing processes.

Improved Inhibitors Targeting the Thymidylate Kinase of Multidrug-Resistant Mycobacterium tuberculosis with Favorable Pharmacokinetics

This study aims to design improved inhibitors targeting the thymidylate kinase (TMK) of Mycobacterium tuberculosis (Mtb), the causative agent of infectious disease tuberculosis that is associated with high morbidity and mortality in developing countries. TMK is an essential enzyme for the synthesis of bacterial DNA. We have performed computer-aided molecular design of MtbTMK inhibitors by modification of the reference crystal structures of the lead micromolar inhibitor TKI1 1-(1-((4-(3-Chlorophenoxy)quinolin-2-yl)methyl)piperidin-4-yl)-5-methylpyrimidine-2,4(1H,3H)-dione bound to TMK of Mtb strain H37Rv (PDB entries: 5NRN and 5NR7) using the computational approach MM-PBSA. A QSAR model was prepared for a training set of 31 MtbTMK inhibitors with published inhibitory potencies () and showed a significant correlation between the calculated relative Gibbs free energies of the MtbTMK–TKIx complex formation and the observed potencies. This model was able to explain approximately 95% of the variation in the in vitro inhibition data and validated our molecular model of MtbTMK inhibition for the subsequent design of new TKI analogs. Furthermore, we have confirmed the predictive capacity of this complexation QSAR model by generating a 3D QSAR PH4 pharmacophore-based model. A satisfactory correlation was also obtained for the validation PH4 model of MtbTMK inhibition (R2 = 0.84). We have extended the hydrophobic m-chloro-phenoxyquinolin-2-yl group of TKI1 that can occupy the entry into the thymidine binding cleft of MtbTMK by alternative larger hydrophobic groups. Analysis of residue interactions at the enzyme binding site made it possible to select suitable building blocks to be used in the preparation of a virtual combinatorial library of 28,900 analogs of TKI1. Structural information derived from the complexation model and the PH4 pharmacophore guided the in silico screening of the library of analogs and led to the identification of new potential MtbTMK inhibitors that were predicted to be effective in the low nanomolar concentration range. The QSAR complexation model predicted an inhibitory concentration of 9.5 nM for the best new virtual inhibitor candidate TKI 13_1, which represents a significant improvement in estimated inhibitory potency compared to TKI1. Finally, the stability of the MtbTMK–inhibitor complexes and the flexibility of the active conformation of the inhibitors were assessed by molecular dynamics for five top-ranking analogs. This computational study resulted in the discovery of new MtbTMK inhibitors with predicted enhanced inhibitory potencies, which also showed favorable predicted pharmacokinetic profiles.

Shamrock‐Shaped D2–A–Cz Materials Featuring Trifluoromethyl Carbazole and Pyrimidine: a Tailored Host for Green Phosphorescent OLEDs

AbstractA new class of shamrock‐shaped D2–A–Cz and D2–A–D′ bipolar host materials is specifically designed to optimize performance in green phosphorescent organic light‐emitting diode (OLED) devices. These materials utilize 3,6‐bis(trifluoromethyl)‐9H‐carbazole (CF3Cz) as the donor (D), and pyrimidine (Pym) or pyridine (Py) as the acceptor, with features of structural modifications aimed at enhancing stability and luminescence efficiency. In particular, the introduction of strong electron‐withdrawing CF3 groups helps stabilize the highest occupied molecular orbital (HOMO) energy level, while electron‐donating groups like tert‐butyl group, carbazole, and N,N‐dimethylamine destabilize the lowest unoccupied molecular orbital (LUMO), resulting in high triplet energy levels crucial for green OLED performance. CF3Cz–2CzPym exhibits outstanding electroluminescent properties when doped with Ir(ppy)3, achieving a maximum external quantum efficiency (EQE) of 18.5% and a luminance efficiency of 64.6 cd A−1 with a low turn‐on voltage of 2.6 V. Additionally, when combined with the electron‐transporting material bis‐4,6‐(3,5‐di‐3‐pyridylphenyl)‐2‐methylpyrimidine (B3PyMPM) to form a co‐host system, these materials further improve charge balance and green OLED efficiency, attaining a maximum EQE of 19.8% and a peak luminescence efficiency of 68.4 cd A−1. The strong electron‐withdrawing CF3 substituents at the 3 and 6 positions of carbazole firmly stabilizes the frontier molecular orbitals with high triplet energy.

Chitosan-Based Porous Carbon Materials with Built-In Lewis Acid Boron Sites for Enhanced CO2 Capture and Conversion via an Electron-Inducing Effect.

Electron-induced effects, which are prevalent in adsorption and heterogeneous catalytic reactions, can significantly influence the state and uptake of adsorbates. Here, we demonstrate the in situ doping of electron-deficient boron into the backbone of chitosan-based porous carbon materials. Despite a reduction in specific surface area, the resulting boron-doped porous carbons (NBPCs) exhibit an enhanced CO2 adsorption performance, with sample NBPC-10 achieving CO2 adsorption capacities of 7.62 and 4.82 mmol·g-1 at 273 and 298 K, respectively. This improvement is attributed to the electron-induced effect of boron doping, which also enhances the separation selectivity of CO2 from N2. Additionally, the high CO2 adsorption capacity fosters synergism between NBPCs and the cocatalyst tetrabutylammonium bromide (TBAB), thereby augmenting the catalytic activity for the cycloaddition of CO2 and epoxide. Notably, cyclic carbonate yields exceeding 99% were attained even under 1 bar of CO2. Controlled experiments corroborated the pivotal role of boron-doping-induced modifications in the porous carbon structure in enhancing both CO2 selective adsorption and conversion performance. Furthermore, NBPCs demonstrated excellent recyclability as both adsorbents and catalysts, offering fresh perspectives for the design of functionalized porous carbon materials tailored for CO2 capture and conversion.

Carbon-carbon triple bond cleavage and reconstitution to achieve aryl amidation using nitrous acid esters

C–C bond cleavage and recombination provide an efficient strategy for the modification and reconstruction of molecule structures. Herein, we present a method for achieving amidation of aryl C(sp2)–H bond through the cleavage and recombination of C–C triple bond with the involvement of nitrous acid esters. This method marks the instance of precise and controlled stepwise cleavage of C–C triple bond, offering a fresh perspective for the cleavage of such bonds. Nitrous acid ester serves as both a radical source and a hydrogen atom transfer (HAT) reagent to functionalize and utilize the two carbon atoms of the C–C triple bond. The alkoxy radical captures the hydrogen atom from the aryl C(sp2)–H bond or N-hydroxyl to induce the 1,3-oxygen radical migration, which is crucial for the subsequent cleavage of the C–C bond.

Noise Reduction Using Synthetic Microjet Excitation in Supersonic Rectangular Jets

This work explores a potential methodology for rectangular jet noise reduction that employs nozzle unsteady microjet excitation. Using high-fidelity computational studies and spectral analyses, major jet noise sources impacted by the applied actuation are identified. A heated supersonic rectangular jet is considered with a nozzle aspect ratio of 2:1 at a Mach number of 1.5. The current study essentially validates the hypothesis of a previous reduced-order analysis that predicted jet noise reduction through jet excitation at the harmonic or subharmonic of the dominant frequency associated with jets’ large-scale structures. Such noise reduction was attributed to the excitation-induced nonlinear energy exchange between the coherent modes. In the current study, the synthetic microjet actuation of the jet plume shear layer using 1% of the jet mass flow rate is implemented at the excitation ports located at the nozzle lip and directed along the jet axis. A resulting jet noise reduction of up to 4 dB at the peak radiation angle is predicted. An analysis of the near-field Spectral Proper Orthogonal Decomposition (SPOD) results provides further insights into the impact of jet actuation on the modification of jet flow structures, thus addressing the effectiveness of the proposed noise control methodology.

Synthesis of Mn-Doped CrFe2O4 Nanoparticles and Their Composite with CNTs: Advanced Structural and Electronic Modifications for High-Efficiency Pollutant Degradation

Synthesis of Mn-Doped CrFe2O4 Nanoparticles and Their Composite with CNTs: Advanced Structural and Electronic Modifications for High-Efficiency Pollutant Degradation

Decoration of Silver Nanoparticles on WS2-WO3 Nanosheets: Implications for Surface-Enhanced Resonance Raman Spectroscopy Detection and Material Characteristics

This study investigates the chemical and structural modifications of vertically aligned tungsten disulfide–tungsten trioxide (WS2-WO3) nanosheets decorated with silver nanoparticles (Ag(NPs)) under nitrogen plasma conditions. The synthesized vertically aligned WS2-WO3 nanosheets were functionalized through direct-current (DC) magnetron sputtering, forming silver-decorated samples. Structural changes, as well as the size and distribution of Ag(NPs), were characterized using scanning electron microscopy (SEM). Chemical state analysis was conducted via X-ray photoelectron spectroscopy (XPS), while Raman spectroscopy was employed to investigate vibrational modes. The findings confirmed the successful decoration of Ag(NPs) and identified unexpected compound transformations that were dependent on the duration of functionalization. The synthesized and functionalized samples were evaluated for their sensing capabilities towards Rhodamine B (RhB) through surface-enhanced resonance Raman scattering (SERRS). This study discusses the impact of substrate morphology and the shape and size of nanoparticles on the enhancement of SERRS mechanisms, achieving an enhancement factor (EF) of approximately 1.6 × 106 and a limit of detection (LOD) of 10−9 M.

Structural Modifications for Tuning Performance and Operational Modes in n-Type Organic Electrochemical Transistors.

Organic mixed ionic-electronic conductors (OMIECs) are crucial in defining the operational modes and performance of organic electrochemical transistors (OECTs). However, studies on the design and structure-performance correlations of small-molecule n-type OMIECs remain scarce. Herein, we designed and synthesized a series of naphthalene diimide (NDI)-based n-type small molecules by extending π-conjugation and increasing the number of electron-withdrawing groups, achieving performance optimization and even changes in operational modes through structural regulations. OECTs based on 4Br-NDI-3EG exhibit a low threshold voltage of -0.022 V, which is the lowest reported for n-type channel materials to date. NDI-DTYA-3EG, synthesized through π-expansion of 4Br-NDI-3EG, maintains a low threshold voltage of -0.041 V and achieves 2 orders of magnitude improvement in electron mobility (1.04 × 10-2 cm2 V-1 s-1) owing to its mixed edge-on and face-on orientation. Specifically, by further increasing the number of electron-withdrawing groups, NDI-DTYM-3EG attains a sufficiently low LUMO energy level (-4.51 eV), enabling a spontaneous reduction in 0.1 M NaCl solution without external bias, thereby achieving self-doping. Consequently, it exhibits n-depletion-mode characteristics with a transconductance value of 287 μS. Moreover, devices made with NDI-DTYM-3EG show exceptional stability, retaining 98% of the initial drain current after 150 min operation. These results provide insights into the understanding and design of n-type mixed ionic-electronic conductor materials.

Impacts of amino acid-linked platinum(II) complexes on DNA structure.

The discovery of cisplatin (cisPt) as an effective anticancer agent was a milestone in the health industry. Despite its success, undesired side effects and acquired resistance still limit the therapeutic usefulness of cisPt. Intrastrand adduct formation at consecutive purines and structural modifications of DNA caused by platinum(II) complexes are important factors for antitumor efficacy. In this study, we examined amino acid-linked platinum(II) complexes, collectively referred to as AAPt, for antiproliferative activity and ability to induce DNA bending. The antiproliferative activity of one AAPt complex tested against a prostate cancer cell line was comparable to that of cisPt, whereas only activity of the AAPt complex was lower in a normal human prostate cell line. Various AAPt analogues were examined for impact on the structures of DNAs with four different purine dinucleotide target sites (GG, AG, GA, and AA) and compared to the parent cisPt. The roles of side-chain identity, chirality, and coordination type (e.g., (N,O) vs. (N,N)) of AAPt complexes are discussed with respect to DNA adduct formation and ability to induce DNA bending. Although the AAPt complexes display different nucleotide preferences (A for AAPt vs. G for cisPt), DNAs containing GG-platinum adducts display a greater degree of bending compared to DNAs with AA-platinum adducts.

Optimizing Therapeutics for Intratumoral Cancer Treatments: Antiproliferative Vanadium Complexes in Glioblastoma

Glioblastoma, an aggressive cancer, is difficult to treat due to its location, late detection, drug resistance, and poor absorption of chemotherapeutics. Intratumoral drug administration offers a promising potential treatment alternative with localized delivery and minimal systemic toxicity. Vanadium(V) coordination complexes, incorporating Schiff base and catecholate ligands, have shown effects as antiproliferative agents with tunable efficacy and reactivity, stability, steric bulk, hydrophobicity, uptake, and toxicity optimized for the intratumoral administration vehicle. A new series of oxovanadium(V) Schiff base–catecholate complexes were synthesized and characterized using nuclear magnetic resonance (NMR), UV-Vis, and infrared spectroscopy and mass spectrometry. Stability under physiological conditions was assessed via UV-Vis spectroscopy, and the antiproliferative activity was evaluated in T98G glioblastoma and SVG p12 normal glial cells using viability assays. The newly synthesized [VO(3-tBuHSHED)(TIPCAT)] complex was more stable (t1/2 ~ 4.5 h) and had strong antiproliferative activity (IC50 ~ 1.5 µM), comparing favorably with the current lead compound, [VO(HSHED)(DTB)]. The structural modifications enhanced stability, hydrophobicity, and steric bulk through substitution with iso-propyl and tert-butyl groups. The improved properties were attributed to steric hindrance associated with the new Schiff base and catecholato ligands, as well as the formation of non-toxic byproducts upon degradation. The [VO(3-tBuHSHED)(TIPCAT)] complex emerges as a promising candidate for glioblastoma therapy by demonstrating enhanced stability and a greater selectivity, which highlights the role of strategic ligand design in developing localized therapies for the treatment of resistant cancers. In reporting the new class of compounds effective against T98G glioblastoma cells, we describe the generally desirable properties that potential drugs being developed for intratumoral administration should have.

Modification of Structure, Pasting, and In Vitro Digestion Properties of Glutinous Rice Starch by Different Lactic Acid Bacteria Fermentation

Modification of Structure, Pasting, and In Vitro Digestion Properties of Glutinous Rice Starch by Different Lactic Acid Bacteria Fermentation

Recent advances in graphitic carbon nitride-based nanocomposites for energy storage and conversion applications.

Graphitic carbon nitride (g-C3N4) has gained significant attention as a promising nonmetallic semiconductor photocatalyst due to its photochemical stability, favorable electronic properties, and efficient light absorption. Nevertheless, its practical applications are hindered by limitations such as low specific surface area, rapid recombination of photogenerated charge carriers, poor electrical conductivity, and restricted photo-response ranges. This review explores recent advancements in the synthesis, modification and application of g-C3N4 and its nanocomposites with a focus on addressing these challenges. Key strategies for enhancing g-C3N4 include various synthesis methods (solvothermal, microwave-assisted, sol-gel, and vapor deposition), doping, defect engineering, heterojunction formation, and surface modifications. Their potential in energy storage and conversion applications, including photocatalytic hydrogen production, carbon dioxide reduction, nitrogen fixation, and electrochemical energy storage are also highlighted. Overall, the review underscores the importance of structural and morphological modifications in improving the photoelectrochemical performance of g-C3N4-based nanocomposites, providing insights for future development and optimization.

The Application of the Pyrazole Structure in the Structural Modification of Natural Products.

Most natural products in nature have broad but not exceedingly good biological activities. The pyrazole structure has been introduced into natural products due to its suitability for various synthetic methods and its broad pharmacological activities. This article provides a detailed introduction to the anti-inflammatory, antibacterial, antifungal, antiviral, and anti-Alzheimer disease activities of pyrazole-modified natural product derivatives, particularly their anti-tumor activity. It is worth noting that compared to lead compounds, most natural product derivatives modified with pyrazole exhibit excellent pharmacological activity. Some of these derivatives exhibit outstanding anti-tumor activity, with IC50 values reaching nanomolar levels. This review provides more research directions and choices for future studies on natural products.

Elucidating the physicochemical interactions between fibrinogen and surfactant mixtures: Implications for pharmaceutical sciences.

This study investigates the physicochemical interactions between fibrinogen (Fib), a key glycoprotein in blood clotting, and a mixture of two biologically active compounds: dicloxacillin (Diclox), an antibiotic; and cetyltrimethylammonium bromide (CTAB), a cationic surfactant. Understanding these interactions is crucial for enhancing drug delivery systems and optimizing pharmaceutical formulations. Molecular docking simulations and various spectroscopic techniques, including UV-Vis, fluorescence, and circular dichroism, were employed to explore how this mixture affects the structural and functional properties of fibrinogen. The docking results revealed that the binding affinity of the dicloxacillin-CTAB mixture with fibrinogen was stronger than either compound individually, suggesting a synergistic interaction. Spectroscopic analysis confirmed structural modifications in the fibrinogen molecule, notably in α-helix content and aromatic residues, indicating loosening or unfolding in protein conformation upon ligand binding. Thermodynamic analyses further supported that the binding process was driven by hydrophobic interactions and electrostatic forces, contributing to stable complex formation. This study advances the current understanding of protein-ligand interactions by exploring the synergistic effects of a dual-ligand system, a novel approach that has not been comprehensively explored in previous literature. These findings provide new insights into the design of drug delivery systems, offering potential applications for improving the efficacy and safety of pharmaceutical formulations targeting fibrinogen-related conditions.