{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T03:16:32Z","timestamp":1770261392801,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-136\/2025-03\/200378"],"award-info":[{"award-number":["451-03-136\/2025-03\/200378"]}]},{"name":"German Academic Exchange Service DAAD PPP","award":["57656312"],"award-info":[{"award-number":["57656312"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Two structurally tunable (propyl-3-ol)triphenyltin(IV) (Ph3SnL1) and (butyl-4-ol)triphenyltin(IV) (Ph3SnL2) compounds were investigated at the human serum transferrin (Tf) molecular interface to resolve how ligand architecture and protein metallation modulate organotin(IV) biocompound stability and lobe-selective binding. Steady-state fluorescence spectroscopy revealed efficient quenching of native Tf emission (\u03bbex = 280 nm, 296\u2013310 K, pH 7.4) without significant spectral displacement, indicating the predominant formation of non-fluorescent ground-state complexes. Calculated bimolecular quenching constants (Kq ~1012 M\u22121 s\u22121) exceeded the diffusion-controlled aqueous limit, ruling out a collisional dynamic quenching mechanism and confirming static complexation as the principal origin of fluorescence suppression. Double-log binding analysis revealed moderate affinity (Ka ~102\u2013103 M\u22121) and an approximately single dominant binding event per protein (n \u2248 0.65\u20130.90). Temperature-dependent van\u2019t Hoff evaluation yielded positive \u0394H\u00b0 and \u0394S\u00b0 values, supporting a spontaneous, entropy-favored association process largely governed by hydrophobic and dispersion-type contributions, consistent with lipophilic organotin(IV) scaffold accommodation. Iron (Fe3+) loading of Tf markedly enhanced ligand engagement, especially for Ph3SnL1, evidencing that metallation-induced lobe closure reshapes pocket accessibility and local polarity relevant for organotin(IV) binding presentation rather than simply strengthening empirical docking scores. Molecular docking localized the most stable Ph3SnL2 poses in the sterically confined, rigid C-lobe, while Ph3SnL1 preferentially penetrated the more adaptive N-lobe. ONIOM QM\/MM refinement of docking poses confirmed strong interfacial stabilization (\u0394Eint \u2248 \u201338 to \u201362 kcal mol\u22121) and clarified charge\u2013packing interplay without invoking frontier orbital analysis. The results map multiscale structure\u2013interaction relationships defining lobe preference and complex stability at the transferrin interface.<\/jats:p>","DOI":"10.3390\/ma19030457","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T18:35:56Z","timestamp":1769193356000},"page":"457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling the Bio-Interface via Spectroscopic and Computational Studies of (Propyl-3-ol\/butyl-4-ol)triphenyltin(IV) Compound Binding to Human Serum Transferrin"],"prefix":"10.3390","volume":"19","author":[{"given":"\u017diko","family":"Milanovi\u0107","sequence":"first","affiliation":[{"name":"Institute for Information Technologies, University of Kragujevac, Liceja Kne\u017eevine Srbije 1A, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9708-2326","authenticated-orcid":false,"given":"Emina","family":"Mrkali\u0107","sequence":"additional","affiliation":[{"name":"Institute for Information Technologies, University of Kragujevac, Liceja Kne\u017eevine Srbije 1A, 34000 Kragujevac, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jovan","family":"Kuli\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Fo\u010da, University of East Sarajevo, 73300 Fo\u010da, Bosnia and Herzegovina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5168-1000","authenticated-orcid":false,"given":"Goran N.","family":"Kalu\u0111erovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Engineering and Natural Sciences, University of Applied Sciences Merseburg, Eberhard-Leibnitz-Stra\u00dfe 2, 06217 Merseburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/aoc.331","article-title":"Organotin compounds and their therapeutic potential: A report from the Organometallic Chemistry Department of the Free University of Brussels","volume":"16","author":"Gielen","year":"2002","journal-title":"Appl. Organomet. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0010-8545(01)00399-X","article-title":"Organotin(IV) compounds formed with biologically active ligands: Equilibrium and structural studies, and some biological aspects","volume":"224","author":"Pellerito","year":"2002","journal-title":"Coord. Chem. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1515\/revic-2018-0014","article-title":"Recent advances in the structural chemistry of organotin(IV) compounds","volume":"39","author":"Rabiee","year":"2019","journal-title":"Rev. Inorg. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1007\/s10904-024-03019-1","article-title":"From simple organotin(IV) complexes to macromolecules: A review inspired by Professor Charles Carraher","volume":"34","author":"Momeni","year":"2024","journal-title":"J. Inorg. Organomet. Polym. Mater."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gielen, M., and Tiekink, E.R. (2005). Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine, Wiley.","DOI":"10.1002\/0470864052"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ccr.2007.12.026","article-title":"Antiproliferative and anti-tumor activity of organotin compounds","volume":"253","author":"Hadjikakou","year":"2009","journal-title":"Coord. Chem. Rev."},{"key":"ref_7","first-page":"340","article-title":"Review of organotin compounds: Chemistry and applications","volume":"2","author":"Ghazi","year":"2018","journal-title":"Int. J. Res. Eng. Innov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e7656","DOI":"10.1002\/aoc.7656","article-title":"Organotin(IV) compounds: Synthesis, characterization, DFT, and molecular docking studies unveiling their biomedical potential","volume":"38","author":"Mansour","year":"2024","journal-title":"Appl. Organomet. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104055","DOI":"10.1016\/j.drudis.2024.104055","article-title":"Recent advances in interaction studies of anticancer metal-based drugs with DNA and RNA targets","volume":"29","author":"Khan","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/s41573-021-00240-2","article-title":"Ligand binding at the protein\u2013lipid interface: Strategic considerations for drug design","volume":"20","author":"Payandeh","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0010-8545(95)01216-8","article-title":"Tin-based antitumour drugs","volume":"151","author":"Gielen","year":"1996","journal-title":"Coord. Chem. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.jconrel.2011.11.028","article-title":"Clinical impact of serum proteins on drug delivery","volume":"161","author":"Kratz","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_13","unstructured":"Gupta, R.C. (2021). Role of transferrin: An iron-binding protein in health and diseases. Nutraceuticals, Academic Press."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1016\/j.ccr.2013.01.024","article-title":"Specific metal ion binding sites in unstructured protein regions","volume":"257","author":"Kozlowski","year":"2013","journal-title":"Coord. Chem. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111459","DOI":"10.1016\/j.chemphys.2022.111459","article-title":"Spectroscopic and molecular docking approach of the interaction of vitamins with human serum transferrin","volume":"555","author":"Cazacu","year":"2022","journal-title":"Chem. Phys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e2728","DOI":"10.1002\/jmr.2728","article-title":"Investigating the interaction of anticancer drug temsirolimus with human transferrin: Molecular docking and spectroscopic approach","volume":"31","author":"Shamsi","year":"2018","journal-title":"J. Mol. Recognit."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9613","DOI":"10.1080\/07391102.2021.1934545","article-title":"Probing the interaction of fisetin with human serum transferrin via spectroscopic and molecular docking approaches","volume":"40","author":"Sandu","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_18","first-page":"e03127","article-title":"Structure prediction of transferrin receptor protein 1 (TfR1) by homology modelling, docking, and molecular dynamics simulation studies","volume":"6","author":"Makki","year":"2020","journal-title":"Heliyon"},{"key":"ref_19","unstructured":"Leach, A.R. (2001). Molecular Modelling: Principles and Applications, Wiley."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/nrd1549","article-title":"Docking and scoring in virtual screening for drug discovery: Methods and applications","volume":"3","author":"Kitchen","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18984","DOI":"10.1039\/C6DT03519A","article-title":"Functionalized mesoporous silica SBA-15 as a carrier for organotin systems against A2780 ovarian carcinoma","volume":"45","author":"Bensing","year":"2016","journal-title":"Dalton Trans."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"213054","DOI":"10.1016\/j.bioadv.2022.213054","article-title":"Effect of chain length on cytotoxic activity of (alkyl-\u03c9-ol)triphenyltin(IV) loaded into SBA-15 silica and in vivo evaluation of Ph3Sn(CH2)8OH delivery","volume":"140","author":"Bensing","year":"2022","journal-title":"Biomater. Adv."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lakowicz, J.R. (2006). Principles of Fluorescence Spectroscopy, Springer.","DOI":"10.1007\/978-0-387-46312-4"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.1021\/bi00514a017","article-title":"Thermodynamics of protein association reactions: Forces contributing to stability","volume":"20","author":"Ross","year":"1981","journal-title":"Biochemistry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"137049","DOI":"10.1016\/j.molstruc.2023.137049","article-title":"Structural properties of new 4,7-dihydroxycoumarin derivatives as potential coagulation inhibitors","volume":"1298","year":"2024","journal-title":"J. Mol. Struct."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ami\u0107, A., Cagardov\u00e1, D.M., and Milanovi\u0107, \u017d. (2025). Theoretical study of antioxidant\/prooxidant potency of protocatechuic aldehyde. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26010404"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111034","DOI":"10.1016\/j.cbi.2024.111034","article-title":"Antioxidant\/prooxidative enzyme-inhibition mechanisms of natural furanocoumarins: Kinetic DFT insights","volume":"396","year":"2024","journal-title":"Chem.-Biol. Interact."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Milisavljevi\u0107, K., and Milanovi\u0107, \u017d. (2025). Multifunctional Tetrahydrocannabinol Derivatives as Potential Antioxidant Neuroprotectors: Computer-Aided Design and Analysis. J. Comput. Biophys. Chem., 1\u201323.","DOI":"10.1142\/S2737416525501170"},{"key":"ref_30","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., and Petersson, G.A. (2016). Gaussian 16, Revision C.01, Gaussian, Inc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1021\/ct0502763","article-title":"Density functional design for thermochemistry and noncovalent interactions","volume":"2","author":"Zhao","year":"2006","journal-title":"J. Chem. Theory Comput."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"154101","DOI":"10.1063\/1.2065267","article-title":"A density-functional model of the dispersion interaction","volume":"123","author":"Becke","year":"2005","journal-title":"J. Chem. Phys."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature10823","article-title":"Structural basis for iron piracy by pathogenic Neisseria","volume":"483","author":"Noinaj","year":"2012","journal-title":"Nature"},{"key":"ref_34","unstructured":"Dassault Syst\u00e8mes (2021). BIOVIA Discovery Studio 2021, Dassault Syst\u00e8mes Biovia."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0092-8674(04)00130-8","article-title":"Structure of the human transferrin receptor\u2013transferrin complex","volume":"116","author":"Cheng","year":"2004","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B","article-title":"Docking via Lamarckian genetic algorithm","volume":"19","author":"Morris","year":"1998","journal-title":"J. Comput. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5678","DOI":"10.1021\/cr5004419","article-title":"ONIOM method and applications","volume":"115","author":"Chung","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"\u017divkovi\u0107, N., Mrkali\u0107, E., Jeli\u0107, R., Tomovi\u0107, J., Odovi\u0107, J., Serafinovi\u0107, M.\u0106., and Sovrli\u0107, M. (2025). The Molecular Recognition of Lurasidone by Human Serum Albumin: A Combined Experimental and Computational Approach. Molecules, 30.","DOI":"10.3390\/molecules30071420"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e202500646","DOI":"10.1002\/cmdc.202500646","article-title":"Multitarget Anticancer Activity of Pyrazoline-Based Hybrids: Insights into Apoptosis, Bovine Serum Albumin\/DNA Interactions, and Caspase Targeting","volume":"20","year":"2025","journal-title":"ChemMedChem"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"16089","DOI":"10.1021\/acsomega.3c09792","article-title":"Evaluation of the Binding Mechanism of Dietary Phytochemical, Ellagic Acid, with Human Transferrin: Spectroscopic, Calorimetric, and Computational Approaches Targeting Neurodegenerative Diseases","volume":"9","author":"Alrouji","year":"2024","journal-title":"ACS Omega"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/iub.1602","article-title":"Iron chemistry at the service of life","volume":"69","author":"Sabio","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1023\/A:1020259021641","article-title":"Reduction of ferric iron as an essential biological process","volume":"15","author":"Pierre","year":"2002","journal-title":"Biometals"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1021\/cr980430w","article-title":"Transferrin as a metal ion mediator","volume":"99","author":"Sun","year":"1999","journal-title":"Chem. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/j.1432-1033.1996.0387r.x","article-title":"Metal binding strength rationalization in human serum transferrin","volume":"242","author":"Li","year":"1996","journal-title":"Eur. J. Biochem."},{"key":"ref_45","first-page":"1","article-title":"Unraveling the binding mechanism of olanzapine with human serum transferrin: Multispectroscopic and computational investigation","volume":"2025","year":"2025","journal-title":"Mol. Divers."}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/19\/3\/457\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T12:54:51Z","timestamp":1770209691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/19\/3\/457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":45,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ma19030457"],"URL":"https:\/\/doi.org\/10.3390\/ma19030457","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]}}}