Journal of Computer-Aided Molecular Design最新文献

{"title":"Antitumor evaluation of novel alizarin-based derivatives through biological and computational approaches","authors":"Tamara Todorović,&nbsp;Jovana Muškinja,&nbsp;Željko Žižak,&nbsp;Tatjana Stanojković,&nbsp;Tina Andrejević,&nbsp;Žiko Milanović,&nbsp;Violeta Marković","doi":"10.1007/s10822-025-00736-8","DOIUrl":"10.1007/s10822-025-00736-8","url":null,"abstract":"<div><p>Two series of alizarine derivatives containing vanillin scaffold (<b>10a-h</b>) or aromatic amide function (<b>12a-h</b>) were synthesized and structurally characterized. The cytotoxic evaluation revealed higher activity towards leukemia cancer cell lines (K562 and HL-60) than solid tumor cells (HeLa and MCF-7). The compound <b>10 h</b>, containing a benzyl group, showed the most prominent activity against K562 cells, and the lowest toxicity towards healthy cells among all active derivatives. The most active compounds <b>10f</b>, <b>10 h</b>, and <b>12 h</b> were further investigated and induced a significant increase in the percentage of HeLa, K562, and HL-60 cells in the subG1 cell cycle phase in comparison with the control cells. Compounds <b>10f</b> and <b>10 h</b> activated apoptosis in K562 cells through all three tested caspases, while derivative <b>12 h</b> only induced the activation of the main effector caspase-3. Molecular docking simulations suggest that these compounds can form stable complexes with caspase-3, consistent with their experimentally confirmed involvement in caspase-dependent apoptotic pathways. All three tested derivatives demonstrated moderate to strong binding to bovine serum albumin (BSA), with preferential occupation of subdomain IIA (site I), as supported both experimentally and through docking studies. The interaction study of these compounds with DNA indicated their ability to interact with ct-DNA through the minor groove.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico-driven protocol for hit-to-lead optimization: a case study on PDE9A inhibitors","authors":"Hiroyuki Ogawa,&nbsp;Masateru Ohta,&nbsp;Mitsunori Ikeguchi","doi":"10.1007/s10822-025-00729-7","DOIUrl":"10.1007/s10822-025-00729-7","url":null,"abstract":"<div><p>Hit-to-lead (H2L) optimization is a critical stage in small-molecule drug discovery, where efficient exploration of chemical space is required to identify promising lead compounds. Conventional H2L workflows rely on iterative synthesis and experimental evaluation, which limit the range of chemical space that can be explored. In contrast, in silico approaches enable efficient selection of promising compounds from a much larger chemical space by generating large numbers of virtual compounds and evaluating them computationally. To harness this potential, we developed an in silico–driven H2L protocol that integrates molecular generation, binding affinity prediction based on relative binding free energies calculated using the non-equilibrium switching (NES) method, and the evaluation of key properties—such as solubility, metabolic stability, and membrane permeability—using machine learning (ML) techniques. In this study, within the context of H2L optimization, we examined the applicability, accuracy, and utility of NES, a relatively new high-precision binding free energy calculation method, and evaluated its effectiveness in large-scale exploration of substituent space. The phosphodiesterase 9A inhibitor was used as a model system. Starting from the reported high-throughput screening hit compound, we first modified the core structure and then sequentially conducted large-scale exploration of two substitution sites. Following this protocol, we narrowed down compounds predicted to those exhibiting not only high binding affinity but also favorable physicochemical and ADME-related properties. Among these, we verified whether the lead compound reported in the literature was included, and confirmed that it appeared as one of the top-ranked candidates. These results demonstrate that an in silico protocol combining large-scale molecular generation, high-accuracy affinity prediction using NES, and ML-based ADME prediction enables H2L optimization that considers a broader substituent space.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10822-025-00729-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational study on QSAR modeling, molecular docking, and ADMET profiling of pyrazole-modified catalpol derivatives as prospective dual inhibitors of VEGFR-2/BRAF V600E","authors":"Vivek Dutta Singh,&nbsp;Sumanta Pal,&nbsp;Soumen Kumar Pati,&nbsp;Narendra Nath Ghosh,&nbsp;Manab Mandal","doi":"10.1007/s10822-025-00684-3","DOIUrl":"10.1007/s10822-025-00684-3","url":null,"abstract":"<div><p>Pancreatic and Esophageal cancers are highly aggressive with high mortality and limited treatment, causing over 466,000 and 544,100 deaths worldwide in 2020 respectively. This highlights the urgent need for safer,and effective anticancer agents<b>.</b> Catalpol, a natural iridoid glycoside, shows anticancer potential, but due to its poor drug-like properties it requires structural modification. This study investigates pyrazole-modified catalpol derivatives as dual inhibitors for these cancers using Quantitative Structure Activity Relationship (QSAR) modelling, molecular docking, and pharmacokinetic studies. We analyzed fourteen pyrazole-modified catalpol derivatives with reported IC50values against four cancer cell lines(BxPC-3, PANC-1, Eca109, and EC9706). The molecules were optimized using DensityFunctional Theory (DFT), and 2D molecular descriptors were calculated using PaDEL. QSAR models were developed by utilizing a Genetic Function Algorithm (GFA) and Multiple Linear Regression (MLR) and validated using statistical metrics such as R², Q², R²adj, and R²pred. Docking studies targeted VEGFR-2 and BRAF V600E kinases using AutoDockVina, while ADMET and drug-likeness properties were predicted using SwissADME and pkCSM tools. The external validation R²pred values for BxPC-3, PANC-1, Eca109, and EC9706 cell lines were 0.9412, 0.9535, 0.9981, and 0.9935, respectively. Among the derivatives, compound 3k showed the highest binding affinity for VEGFR-2 (− 8.18 kcal/mol) and BRAF (− 8.64 kcal/mol), surpassing the control drugs etoposide (− 8.00 kcal/mol) and dabrafenib (− 8.15 kcal/mol) respectively. ADMET analysis confirmed good intestinal absorption, limited blood-brain barrier penetration, non-toxicity, acceptable total clearance, and compliance with Lipinski’s rule. Overall, the study suggests that pyrazole-modified catalpol derivatives, especially compound 3k, are promising multi-target inhibitors for pancreatic and esophageal cancers, justify further <i>in-vitro</i> and <i>in-vivo</i> studies.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145779139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular simulations of paclitaxel binding to mutant β-tubulin: insights into chemotherapy resistance","authors":"Paola Vottero,&nbsp;Martina Centroni,&nbsp;Ebenezea Gitari,&nbsp;Philip Winter,&nbsp;Jack Tuszynski,&nbsp;Maral Aminpour","doi":"10.1007/s10822-025-00716-y","DOIUrl":"10.1007/s10822-025-00716-y","url":null,"abstract":"<div><p>Paclitaxel, a cornerstone in cancer chemotherapy, stabilizes microtubules by binding to the β-tubulin taxane site. However, resistance mechanisms, often driven by β-tubulin mutations, undermine its efficacy. While such mutations are known to alter drug sensitivity, their molecular impact on paclitaxel binding remains incompletely understood. Here, we employ molecular docking, molecular dynamics (MD) simulations, and Molecular Mechanics with Generalized Born Surface Area (MM/GBSA) calculations to quantify how clinically relevant β-tubulin mutations affect paclitaxel binding affinity. Root mean square fluctuation (RMSF) analysis was used to assess local structural dynamics near the binding site. Our results show that despite minor variations in docking scores, MM/GBSA analyses revealed significant mutation-induced shifts in binding free energy, particularly for residues near the M loop, H5–H6 helices, and S9–S10 region. Complementary RMSF analysis indicated altered flexibility in several of these regions, suggesting potential disruptions to local stabilization mechanisms. Differences between single- and two-dimer simulations highlight the importance of modeling lateral protofilament contacts when evaluating microtubule-targeting agents. These findings underscore the relevance of structure-based modeling for understanding drug resistance mechanisms and informing the development of mutation-aware taxane therapies.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medt5-bi: bidirectional translation between drug indications and molecular structures using a chemically-aware transformer","authors":"Soham Pahari,&nbsp;M. Srinivas","doi":"10.1007/s10822-025-00728-8","DOIUrl":"10.1007/s10822-025-00728-8","url":null,"abstract":"<div><p>The increasingly complex nature of drug discovery requires new computational approaches to reduce cost and development time. This work introduces a novel bidirectional transformer-based architecture that seamlessly maps natural-language drug indications to Simplified Molecular Input Line Entry System (SMILES) encoded molecular structures. The proposed model MedT5-Bi integrates three key contributions that collectively enhance molecular generation from textual descriptions. First, a Molecule-Aware Embeddings (MAEmb) module fuses MolEmbedder token embeddings with structural insights derived from a Graph Neural Network (GNN) to effectively capturing both sequential and topological features of chemical entities. Second, a Dynamic Attention Mechanism (DAM) adaptively switches between softmax and log-linear attention formulations based on input length and complexity, thereby maintaining performance consistency across varying sequence distributions. Third, the system is fine-tuned via reinforcement learning (RL) using a carefully designed composite reward function that jointly optimizes chemical validity, structural similarity, and fingerprint-based metrics. This RL-based training stage aligns generative outputs with desired chemical properties while improving the model’s generalization across diverse indication inputs. Evaluated on a large, augmented ChEMBL dataset. The proposed architecture outperforms existing state-of-the-art model by 16.6<span>(-)</span>24.8% on standard benchmarks including BLEU, ROUGE, Levenshtein distance, Morgan/Tanimoto similarity, and Text2Mol metrics.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing a multi-epitope mRNA vaccine to combat human metapneumovirus based on consensus sequence using reverse vaccinology","authors":"Ajay Kumar Singhmar,&nbsp;Vinod Goyal,&nbsp;Santosh Kumari,&nbsp;Sapna Grewal","doi":"10.1007/s10822-025-00732-y","DOIUrl":"10.1007/s10822-025-00732-y","url":null,"abstract":"<div><p>Human metapneumovirus (HMPV) ranks among the chief causes of serious respiratory illness in young children, accounting for about 3–10% of hospital admissions for acute lower respiratory tract infections in those under five years of age. Despite recent outbreaks and its rising incidence in recent years, no licensed vaccines or targeted therapies are currently available. In this study, surface viral proteins were selected as antigenic candidates, and their consensus sequences were derived from 782 HMPV genomes. Then using immunoinformatic approaches, immunodominant CTL, HTL, LBL epitopes within these proteins consensus sequence that exhibited high antigenicity, exhibiting no toxicity, no allergenic potential, and broad conservancy across HMPV clades were identified and combined with adjuvants, the PADRE sequence, and linkers for vaccine development. Physicochemical analysis confirmed that the resulting multi‐epitope mRNA vaccine is stable under physiological conditions. Molecular docking analyses revealed robust interactions with important immune receptors and subsequent molecular dynamics simulations validated the stability of these complexes over time. Immune simulations predicted robust humoral and cellular responses. Finally, a Kozak sequence was included to enhance mRNA stability and translational efficiency, followed by an MITD sequence to enhance epitope presentation, a TAA codon to terminate translation, and for stability 5′ UTR and 3′ UTR was added and the engineered mRNA’s secondary structure was predicted. Additionally final vaccine construct was cloned in silico into the pVAX1 vector, and virtual agarose gel electrophoresis was performed. These results support the potential of our multi‐epitope mRNA vaccine as a promising preventive strategy against HMPV infection.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of novel natural product-derived EGFR inhibitors using multiple linear regression, stacked ensemble regression, and fingerprinting approaches","authors":"Said Bitam,&nbsp;Mabrouk Hamadache,&nbsp;Salah Hanini","doi":"10.1007/s10822-025-00731-z","DOIUrl":"10.1007/s10822-025-00731-z","url":null,"abstract":"<div><p>This study developed and validated Quantitative Structure-Activity Relationship models to predict the inhibitory activity (pIC₅₀) of 225 EGFR inhibitors. A genetic algorithm selected eight molecular descriptors, which were used to construct two models: a multiple linear regression (MLR) and a stacked ensemble regression (SER). The SER model showed only marginally higher accuracy (<span>(Delta r^2 = +0.022)</span>) but exhibited greater predictive instability (<span>(Delta r^2_{m(test)} = 0.0802)</span> vs. MLR’s 0.0184) and reduced interpretability. Thus, MLR was retained as the primary model due to its OECD-compliant mechanistic transparency and superior generalizability. Rigorous applicability domain analysis confirmed the MLR model’s reliability. Notably, molecular docking (PDB ID: 8A27) identified a top-ranked inhibitor (Compound 121) with high binding affinity (<span>(-12.023)</span> kcal/mol), forming critical hydrogen bonds and hydrophobic interactions with EGFR’s active site. Virtual screening of 32 structural analogs of Compound 121 revealed additional promising candidates. This work provides a robust framework for EGFR inhibitor discovery, combining computational modeling with structural insights.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics insights into the interactions of biocompatible synthetic polymer composites with carbon-based nanoparticle derivatives: a comparative study of PLGA and PCL interactions with GO/rGO","authors":"Rumeysa Hilal Çelik,&nbsp;Selma Şimşek,&nbsp;Esra Gel,&nbsp;Saliha Ece Acuner","doi":"10.1007/s10822-025-00726-w","DOIUrl":"10.1007/s10822-025-00726-w","url":null,"abstract":"<div><p>Molecular dynamics (MD) simulations are extensively employed in biomedical research to explore atomic-level molecular interactions, with broad applications in drug discovery, tissue engineering, and structural biology. This study uses MD simulations to examine the interaction dynamics between graphene oxide (GO) derivatives and two FDA-approved biocompatible polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL). Custom-built PLGA structures with varying PLA/PGA ratios and PCL were modeled to assess their interactions with GO and reduced graphene oxide (rGO). System stability was evaluated using hydrogen bond occupancy, radius of gyration, potential and binding energies, radial distribution functions, and solvation free energy. Comparative analyses revealed that 75:25 PLGA–GO and 75:25 PLGA–rGO systems exhibited the most stable interaction profiles among PLGA variants, while PCL–GO was the most stable among PCL systems. To our knowledge, this is the first comparative MD study systematically evaluating atomic-scale interactions of GO and rGO with PLGA at different copolymer ratios and with PCL. These findings provide molecular-level insights to guide the design and optimization of polymer–nanoparticle composites for biomedical applications.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div><p>The analysis of interaction dynamics between graphene oxide (GO) derivatives and two biocompatible synthetic polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL), using molecular dynamics (MD) simulations provides valuable molecular-level insights for the rational design and optimization of polymer–nanoparticle composites for future biomedical applications.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145730287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular simulation-based 3D structural construction of olfactory receptor with agonist binding","authors":"Takumi Hirao,&nbsp;Yusuke Ihara,&nbsp;Chiori Ijichi,&nbsp;Genki Kudo,&nbsp;Ryunosuke Yoshino,&nbsp;Takatsugu Hirokawa","doi":"10.1007/s10822-025-00706-0","DOIUrl":"10.1007/s10822-025-00706-0","url":null,"abstract":"<div><p>Olfactory receptors (ORs) form the largest subfamily of class A G protein-coupled receptors (GPCRs); however, only a few 3D structures of ORs have been determined. Structure-based virtual screening and improved structural insights are required to effectively identify novel odor molecules and elucidate their binding modes along with mechanisms of activation and inactivation. Herein, we propose a protocol to provide an active state model for the target OR (OR9Q2) with agonist molecules using AlphaFold2, molecular simulations, and virtual screening. Furthermore, we extracted ligand-stable bound sections using the ligand-stable duration (LSD) protocol defined in this study to analyze conformational ensembles of complex structures. We constructed promising complex structures and demonstrated their reliability by calculating the area under the receiver operating characteristic (ROC) curve in virtual screening tests using experimentally validated active and inactive compounds. This study offers a reliable structure-based screening protocol for olfactory receptors, which can subsequently aid novel odorant discovery and advancing fragrance, flavour, and biosensor industries.</p></div>","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12686088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterization and density functional theory of a novel dichloro(2-(1-anthracene-9-ylmethyl)-1H-1,2,3-triazole-5-yl) pyridine)Cu(II) and polymeric dichloro(2-(1-anthracene-9-ylmethyl)-1H-1,2,3 -triazole-5-yl)pyridine) Cd(II) complexes","authors":"K. M. Tawfiq,&nbsp;Ahmed A. Ismail,&nbsp;S. J. Coles,&nbsp;C. Wilson,&nbsp;J. H. Potgieter,&nbsp;G. J. Miller,&nbsp;Rasha Ahmed Hashim,&nbsp;Aly Abdou,&nbsp;Musa E. Mohamed Babiker,&nbsp;O. A. Farghaly,&nbsp;Ali Y. Alzahrani,&nbsp;Ahmed A. Alzharani,&nbsp;Sameera N. Al-Ghamdi,&nbsp;Antar A. Abdelhamid","doi":"10.1007/s10822-025-00715-z","DOIUrl":"10.1007/s10822-025-00715-z","url":null,"abstract":"&lt;div&gt;&lt;p&gt;A novel dichloro(2-(1-anthracene-9-ylmethyl)-1&lt;i&gt;H&lt;/i&gt;-1,2,3-triazole-5-yl) pyridine) Cu(II) and polymeric dichloro(2-(1-anthracene-9-ylmethyl)-1&lt;i&gt;H&lt;/i&gt;-1,2,3-triazole-5-yl) pyridine) Cd(II) complex compounds have been synthesizing and characterized them by a different of spectroscopic and physicochemical procedures containing UV–visible, IR spectroscopy, mass spectrometry, NMR spectroscopic techniques, together with fluorescence spectroscopy, X-ray, electrochemistry, conductivity, and magnetic susceptibility measurements alongside Density Functional Theory (DFT) calculations. According to the magnetic moment values achieved for the complex d&lt;sup&gt;9&lt;/sup&gt; [Cu(L)&lt;sub&gt;2&lt;/sub&gt;Cl&lt;sub&gt;2&lt;/sub&gt;] gave it an octahedral environment around the copper (II) atom. We confirmed that both [Cu(II)(an-triazole-py)&lt;sub&gt;2&lt;/sub&gt;&lt;i&gt;Cl&lt;/i&gt;&lt;sub&gt;2&lt;/sub&gt;] and [Cd(II))( an-triazole-py)&lt;sub&gt;2&lt;/sub&gt;&lt;i&gt;Cl&lt;/i&gt;&lt;sub&gt;2&lt;/sub&gt;] exhibit stable octahedral geometries. The insights gained from DFT elucidated the electronic structures and reactivity of these complexes, providing a solid theoretical foundation for our experimental findings. However, the results of fluorescence spectroscopy recommend that ligand (L) may be an appropriate agent to identify Cadmium ion. So, this kind of material might have prospective use as a Cd&lt;sup&gt;+2&lt;/sup&gt; sensor. Both the Cd(II) &amp; copper (II) complex materials exhibition effective emission intensity in comparison with L, since the Cd(II) ions are difficult to oxidize or reduce owing to their stable d&lt;sup&gt;10&lt;/sup&gt; configurations. Alternatively, the fluorescent intensity enhancement might be owing to the coordination of free ligand to Cd(II) &amp; Cu(II) decreasing the loss of energy through radiation fewer thermal vibrations of the intra ligand agitated states &amp; owing to a growth in the rigidity of the ligand. Density functional theory (DFT) theory employed as useful in proof the structures of the ligand L (triazole-py)), metal ion complex compounds and examine the quantum chemical properties of this complex. The degree of distortion, &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;4&lt;/sub&gt; = one and zero for perfect tetrahedral and square-planar geometry, individually. The Cu(II) complex had T&lt;sub&gt;4&lt;/sub&gt; = 0.149. This value supported the 3D geometry around the copper (II) complex very close to a square-planar arrangement. The two Cd(II) centers had T&lt;sub&gt;5&lt;/sub&gt; = 0.226 &amp; 0.314, respectively. These values supported the square pyramidal (C&lt;sub&gt;4v&lt;/sub&gt;) environment around the two Cd(II) centers. X-ray diffraction demonstrated that the cadmium ion coordinates to the N&lt;sub&gt;3&lt;/sub&gt; atom of the triazolyl group and nitrogen atom of pyridine nucleus, forming five-membered ring. The donating ability of N3-triazolyl is stronger than that of the N-pyridine, due to the shorter Cd–N (triazole) bonds length compared with the Cd–N-pyridine bond, The collective results alongside with the DFT estimations shown a 1:2 (Metal: Ligand) stoichiometric ratio and the complexes framed with g","PeriodicalId":621,"journal":{"name":"Journal of Computer-Aided Molecular Design","volume":"40 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}