Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties
Three new molecular complexes (phen)<sub>3</sub>(2-amino-Bz)<sub>2</sub>(H<sup>+</sup>)(BF<sub>4</sub><sup>−</sup>)·3H<sub>2</sub>O <b>5</b>, (phen)<sub>3</sub>(2-amino-5(6)-methyl-Bz)<sub>2</sub...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-01-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/29/3/583 |
| _version_ | 1797318464782729216 |
|---|---|
| author | Kameliya Anichina Nikolay Kaloyanov Diana Zasheva Rusi Rusew Rositsa Nikolova Denitsa Yancheva Ventsislav Bakov Nikolai Georgiev |
| author_facet | Kameliya Anichina Nikolay Kaloyanov Diana Zasheva Rusi Rusew Rositsa Nikolova Denitsa Yancheva Ventsislav Bakov Nikolai Georgiev |
| author_sort | Kameliya Anichina |
| collection | DOAJ |
| description | Three new molecular complexes (phen)<sub>3</sub>(2-amino-Bz)<sub>2</sub>(H<sup>+</sup>)(BF<sub>4</sub><sup>−</sup>)·3H<sub>2</sub>O <b>5</b>, (phen)<sub>3</sub>(2-amino-5(6)-methyl-Bz)<sub>2</sub>(H<sup>+</sup>)(BF<sub>4</sub><sup>−</sup>)·H<sub>2</sub>O <b>6</b>, and (phen)(1-methyl-2-amino-Bz)(H<sup>+</sup>)(BF<sub>4</sub><sup>−</sup>) <b>7</b>, were prepared by self-assembly of 1,10-phenanthroline (phen) and various substituted 2-aminobenzimidazoles. Confirmation of their structures was established through spectroscopic methods and elemental analysis. The X-ray diffraction analysis revealed that the crystal structure of <b>7</b> is stabilized by the formation of hydrogen bonds and short contacts. In addition, the molecular geometry and electron structure of molecules <b>5</b> and <b>6</b> were theoretically evaluated using density functional theory (DFT) methods. According to the DFT B3LYP/6-311+G* calculations, the protonated benzimidazole (Bz) units act as NH hydrogen bond donors, binding two phenanthrolines and a BF<sub>4</sub><sup>−</sup> ion. Non-protonated Bz unit form hydrogen bonds with the N-atoms of a third molecule phen. The molecular assembly is held together by π-π stacking between benzimidazole and phenanthroline rings, allowing for N-atoms to associate with water molecules. The complexes were tested in vitro for their tumor cell growth inhibitory effects on prostate (PC3), breast (MDA-MB-231 and MCF-7), and cervical (HeLa) cancer cell lines using MTT-dye reduction assay. The in vitro cytotoxicity analysis and spectrophotometric investigation in the presence of ct-DNA, showed that self-assembled molecules <b>5</b>–<b>7</b> are promising DNA-binding anticancer agents warranting further in-depth exploration. |
| first_indexed | 2024-03-08T03:52:46Z |
| format | Article |
| id | doaj.art-7935ea0917da4ad8ada6492d0b16d4a5 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T03:52:46Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-7935ea0917da4ad8ada6492d0b16d4a52024-02-09T15:18:42ZengMDPI AGMolecules1420-30492024-01-0129358310.3390/molecules29030583Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic PropertiesKameliya Anichina0Nikolay Kaloyanov1Diana Zasheva2Rusi Rusew3Rositsa Nikolova4Denitsa Yancheva5Ventsislav Bakov6Nikolai Georgiev7Department of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, BulgariaDepartment of Organic Chemistry, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, BulgariaLaboratory of Reproductive OMICs Technologies, Acad. Kiril Bratanov Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, 73A Tsarigradsko Shosse Blvd., 1113 Sofia, BulgariaDepartment of Structural Crystallography and Materials Science, Acad. Ivan Kostov Institute of Mineralogy and Crystallography, Bulgarian Academy of Sciences, Acad G. Bonchev Str., Build. 107, 1113 Sofia, BulgariaDepartment of Structural Crystallography and Materials Science, Acad. Ivan Kostov Institute of Mineralogy and Crystallography, Bulgarian Academy of Sciences, Acad G. Bonchev Str., Build. 107, 1113 Sofia, BulgariaDepartment of Organic Chemistry, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, BulgariaDepartment of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, BulgariaDepartment of Organic Synthesis, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, BulgariaThree new molecular complexes (phen)<sub>3</sub>(2-amino-Bz)<sub>2</sub>(H<sup>+</sup>)(BF<sub>4</sub><sup>−</sup>)·3H<sub>2</sub>O <b>5</b>, (phen)<sub>3</sub>(2-amino-5(6)-methyl-Bz)<sub>2</sub>(H<sup>+</sup>)(BF<sub>4</sub><sup>−</sup>)·H<sub>2</sub>O <b>6</b>, and (phen)(1-methyl-2-amino-Bz)(H<sup>+</sup>)(BF<sub>4</sub><sup>−</sup>) <b>7</b>, were prepared by self-assembly of 1,10-phenanthroline (phen) and various substituted 2-aminobenzimidazoles. Confirmation of their structures was established through spectroscopic methods and elemental analysis. The X-ray diffraction analysis revealed that the crystal structure of <b>7</b> is stabilized by the formation of hydrogen bonds and short contacts. In addition, the molecular geometry and electron structure of molecules <b>5</b> and <b>6</b> were theoretically evaluated using density functional theory (DFT) methods. According to the DFT B3LYP/6-311+G* calculations, the protonated benzimidazole (Bz) units act as NH hydrogen bond donors, binding two phenanthrolines and a BF<sub>4</sub><sup>−</sup> ion. Non-protonated Bz unit form hydrogen bonds with the N-atoms of a third molecule phen. The molecular assembly is held together by π-π stacking between benzimidazole and phenanthroline rings, allowing for N-atoms to associate with water molecules. The complexes were tested in vitro for their tumor cell growth inhibitory effects on prostate (PC3), breast (MDA-MB-231 and MCF-7), and cervical (HeLa) cancer cell lines using MTT-dye reduction assay. The in vitro cytotoxicity analysis and spectrophotometric investigation in the presence of ct-DNA, showed that self-assembled molecules <b>5</b>–<b>7</b> are promising DNA-binding anticancer agents warranting further in-depth exploration.https://www.mdpi.com/1420-3049/29/3/583self-assembly1,10-phenanthroline2-aminobenzimidazolesX-ray diffraction analysisDFTantitumor activity |
| spellingShingle | Kameliya Anichina Nikolay Kaloyanov Diana Zasheva Rusi Rusew Rositsa Nikolova Denitsa Yancheva Ventsislav Bakov Nikolai Georgiev Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties Molecules self-assembly 1,10-phenanthroline 2-aminobenzimidazoles X-ray diffraction analysis DFT antitumor activity |
| title | Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties |
| title_full | Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties |
| title_fullStr | Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties |
| title_full_unstemmed | Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties |
| title_short | Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties |
| title_sort | self assembled molecular complexes of 1 10 phenanthroline and 2 aminobenzimidazoles synthesis structure investigations and cytotoxic properties |
| topic | self-assembly 1,10-phenanthroline 2-aminobenzimidazoles X-ray diffraction analysis DFT antitumor activity |
| url | https://www.mdpi.com/1420-3049/29/3/583 |
| work_keys_str_mv | AT kameliyaanichina selfassembledmolecularcomplexesof110phenanthrolineand2aminobenzimidazolessynthesisstructureinvestigationsandcytotoxicproperties AT nikolaykaloyanov selfassembledmolecularcomplexesof110phenanthrolineand2aminobenzimidazolessynthesisstructureinvestigationsandcytotoxicproperties AT dianazasheva selfassembledmolecularcomplexesof110phenanthrolineand2aminobenzimidazolessynthesisstructureinvestigationsandcytotoxicproperties AT rusirusew selfassembledmolecularcomplexesof110phenanthrolineand2aminobenzimidazolessynthesisstructureinvestigationsandcytotoxicproperties AT rositsanikolova selfassembledmolecularcomplexesof110phenanthrolineand2aminobenzimidazolessynthesisstructureinvestigationsandcytotoxicproperties AT denitsayancheva selfassembledmolecularcomplexesof110phenanthrolineand2aminobenzimidazolessynthesisstructureinvestigationsandcytotoxicproperties AT ventsislavbakov selfassembledmolecularcomplexesof110phenanthrolineand2aminobenzimidazolessynthesisstructureinvestigationsandcytotoxicproperties AT nikolaigeorgiev selfassembledmolecularcomplexesof110phenanthrolineand2aminobenzimidazolessynthesisstructureinvestigationsandcytotoxicproperties |