Exploring the Potential of a New Nickel(II):Phenanthroline Complex with L-isoleucine as an Antitumor Agent: Design, Crystal Structure, Spectroscopic Characterization, and Theoretical Insights
This study presents the synthesis, physicochemical characterization, and biological evaluation of a novel ternary nickel(II) complex with isoleucine and 1,10-phenanthroline ligands, [Ni(Phen)(Ile)<sub>2</sub>]∙6H<sub>2</sub>O, designed as a potential antitumor agent. Single-c...
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2025-07-01
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| Online Access: | https://www.mdpi.com/1420-3049/30/13/2873 |
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| author | Jayson C. dos Santos João G. de Oliveira Neto Ana B. N. Moreira Luzeli M. da Silva Alejandro P. Ayala Mateus R. Lage Rossano Lang Francisco F. de Sousa Fernando Mendes Adenilson O. dos Santos |
| author_facet | Jayson C. dos Santos João G. de Oliveira Neto Ana B. N. Moreira Luzeli M. da Silva Alejandro P. Ayala Mateus R. Lage Rossano Lang Francisco F. de Sousa Fernando Mendes Adenilson O. dos Santos |
| author_sort | Jayson C. dos Santos |
| collection | DOAJ |
| description | This study presents the synthesis, physicochemical characterization, and biological evaluation of a novel ternary nickel(II) complex with isoleucine and 1,10-phenanthroline ligands, [Ni(Phen)(Ile)<sub>2</sub>]∙6H<sub>2</sub>O, designed as a potential antitumor agent. Single-crystal X-ray diffraction revealed a monoclinic structure (C2-space group) with an octahedral Ni(II) coordination involving Phen and Ile ligands. A Hirshfeld surface analysis highlighted intermolecular interactions stabilizing the crystal lattice, with hydrogen bonds (H···H and O···H/H···O) dominating (99.1% of contacts). Density functional theory (DFT) calculations, including solvation effects (in water and methanol), demonstrated strong agreement with the experimental geometric parameters and revealed higher affinity to the water solvent. The electronic properties of the complex, such as HOMO−LUMO gaps (3.20–4.26 eV) and electrophilicity (4.54–5.88 eV), indicated a charge-transfer potential suitable for biological applications through interactions with biomolecules. Raman and infrared spectroscopic studies showed vibrational modes associated with Ni–N/O bonds and ligand-specific deformations, with solvation-induced shifts observed. A study using ultraviolet–visible–near-infrared absorption spectroscopy demonstrated that the complex remains stable in solution. In vitro cytotoxicity assays against MCF-7 (breast adenocarcinoma) and HCT-116 (colorectal carcinoma) cells showed dose-dependent activity, achieving 47.6% and 65.3% viability reduction at 100 μM (48 h), respectively, with lower toxicity to non-tumor lung fibroblasts (GM07492A, 39.8%). Supporting the experimental data, we performed computational modeling to examine the pharmacokinetic profile, with particular focus on the absorption, distribution, metabolism, and excretion properties and drug-likeness potential. |
| format | Article |
| id | doaj-art-505e5be3921c4afd8fe78abbdb224f4d |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-505e5be3921c4afd8fe78abbdb224f4d2025-08-20T03:28:32ZengMDPI AGMolecules1420-30492025-07-013013287310.3390/molecules30132873Exploring the Potential of a New Nickel(II):Phenanthroline Complex with L-isoleucine as an Antitumor Agent: Design, Crystal Structure, Spectroscopic Characterization, and Theoretical InsightsJayson C. dos Santos0João G. de Oliveira Neto1Ana B. N. Moreira2Luzeli M. da Silva3Alejandro P. Ayala4Mateus R. Lage5Rossano Lang6Francisco F. de Sousa7Fernando Mendes8Adenilson O. dos Santos9Center for Sciences of Imperatriz, Federal University of Maranhão—UFMA, Imperatriz 65900-410, MA, BrazilCenter for Sciences of Imperatriz, Federal University of Maranhão—UFMA, Imperatriz 65900-410, MA, BrazilCenter for Sciences of Imperatriz, Federal University of Maranhão—UFMA, Imperatriz 65900-410, MA, BrazilCenter for Sciences of Imperatriz, Federal University of Maranhão—UFMA, Imperatriz 65900-410, MA, BrazilDepartment of Physics, Federal University of Ceará—UFC, Fortaleza 65455-900, CE, BrazilCenter for Sciences of Imperatriz, Federal University of Maranhão—UFMA, Imperatriz 65900-410, MA, BrazilInstitute of Science and Technology, Federal University of São Paulo—UNIFESP, São José dos Campos 12231-280, SP, BrazilInstitute of Exact and Natural Sciences, Federal University of Para—UFPA, Belém 66075-110, PA, BrazilDepartment Biomedical Laboratory Sciences, ESTEC-Coimbra Health School, Polytechnic Institute of Coimbra, 3046-854 Coimbra, PortugalCenter for Sciences of Imperatriz, Federal University of Maranhão—UFMA, Imperatriz 65900-410, MA, BrazilThis study presents the synthesis, physicochemical characterization, and biological evaluation of a novel ternary nickel(II) complex with isoleucine and 1,10-phenanthroline ligands, [Ni(Phen)(Ile)<sub>2</sub>]∙6H<sub>2</sub>O, designed as a potential antitumor agent. Single-crystal X-ray diffraction revealed a monoclinic structure (C2-space group) with an octahedral Ni(II) coordination involving Phen and Ile ligands. A Hirshfeld surface analysis highlighted intermolecular interactions stabilizing the crystal lattice, with hydrogen bonds (H···H and O···H/H···O) dominating (99.1% of contacts). Density functional theory (DFT) calculations, including solvation effects (in water and methanol), demonstrated strong agreement with the experimental geometric parameters and revealed higher affinity to the water solvent. The electronic properties of the complex, such as HOMO−LUMO gaps (3.20–4.26 eV) and electrophilicity (4.54–5.88 eV), indicated a charge-transfer potential suitable for biological applications through interactions with biomolecules. Raman and infrared spectroscopic studies showed vibrational modes associated with Ni–N/O bonds and ligand-specific deformations, with solvation-induced shifts observed. A study using ultraviolet–visible–near-infrared absorption spectroscopy demonstrated that the complex remains stable in solution. In vitro cytotoxicity assays against MCF-7 (breast adenocarcinoma) and HCT-116 (colorectal carcinoma) cells showed dose-dependent activity, achieving 47.6% and 65.3% viability reduction at 100 μM (48 h), respectively, with lower toxicity to non-tumor lung fibroblasts (GM07492A, 39.8%). Supporting the experimental data, we performed computational modeling to examine the pharmacokinetic profile, with particular focus on the absorption, distribution, metabolism, and excretion properties and drug-likeness potential.https://www.mdpi.com/1420-3049/30/13/2873nickel(II) complexcrystal growthDFT calculationsHirshfeld surfacesvibrational spectroscopycytotoxicity |
| spellingShingle | Jayson C. dos Santos João G. de Oliveira Neto Ana B. N. Moreira Luzeli M. da Silva Alejandro P. Ayala Mateus R. Lage Rossano Lang Francisco F. de Sousa Fernando Mendes Adenilson O. dos Santos Exploring the Potential of a New Nickel(II):Phenanthroline Complex with L-isoleucine as an Antitumor Agent: Design, Crystal Structure, Spectroscopic Characterization, and Theoretical Insights Molecules nickel(II) complex crystal growth DFT calculations Hirshfeld surfaces vibrational spectroscopy cytotoxicity |
| title | Exploring the Potential of a New Nickel(II):Phenanthroline Complex with L-isoleucine as an Antitumor Agent: Design, Crystal Structure, Spectroscopic Characterization, and Theoretical Insights |
| title_full | Exploring the Potential of a New Nickel(II):Phenanthroline Complex with L-isoleucine as an Antitumor Agent: Design, Crystal Structure, Spectroscopic Characterization, and Theoretical Insights |
| title_fullStr | Exploring the Potential of a New Nickel(II):Phenanthroline Complex with L-isoleucine as an Antitumor Agent: Design, Crystal Structure, Spectroscopic Characterization, and Theoretical Insights |
| title_full_unstemmed | Exploring the Potential of a New Nickel(II):Phenanthroline Complex with L-isoleucine as an Antitumor Agent: Design, Crystal Structure, Spectroscopic Characterization, and Theoretical Insights |
| title_short | Exploring the Potential of a New Nickel(II):Phenanthroline Complex with L-isoleucine as an Antitumor Agent: Design, Crystal Structure, Spectroscopic Characterization, and Theoretical Insights |
| title_sort | exploring the potential of a new nickel ii phenanthroline complex with l isoleucine as an antitumor agent design crystal structure spectroscopic characterization and theoretical insights |
| topic | nickel(II) complex crystal growth DFT calculations Hirshfeld surfaces vibrational spectroscopy cytotoxicity |
| url | https://www.mdpi.com/1420-3049/30/13/2873 |
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