Gil, A.* and Calhorda, M. J.* A Closer Look at Phenanthroline; Amies, W., Ed. Nova Science Publishers, Inc.: New York, 2020; pp 1-66.
1,10-phenanthroline (phen) is a heterocycle consisting of three fused rings, with two pyridines fused on a central benzene. The two nitrogen atoms can bind metals using their lone pairs and make it a strong donor. The extended pi system confers to phen the possibility of acting as a pi-acceptor, strengthening the metal-ligand bond. Organometallic complexes of Mo(IV), [Mo(C5H5)2(phen)][PF6]2 (1), and Mo(II), [Mo(C3H5)Br(CO)2(phen)] (2), have been synthesized and characterized, and many aspects of their chemistry studied. The versatility of phen is well reflected in its functionalization, either by replacing hydrogen atoms by other groups, or by extending the frame to 1,10 phenanthroline-5,6-dione or dipyridophenazine. In all these molecules, the pi electrons of the rings and the substituents may interact with their surroundings by weak interactions, namely with biological molecules (DNA duplexes, G-quadruplexes or proteins), opening the way to therapeutic purposes and medical applications. Complex 2 has displayed high cytotoxic activity towards human cancer cell lines, with IC50 below 5 microM for HeLa. DFT calculations have been performed to understand the nature of the interactions responsible for this effect using different kinds of models and analyzing the results in several ways. It was found that for the phen ligand alone the nature of the interaction with two pairs of bases is mainly ruled by dispersion forces although these cannot by themselves balance the repulsive Pauli interaction. Charge transfer, polarization terms and, specially, the electrostatic contribution, become crucial to produce an attractive interaction. This behavior is followed by methylated and ketonic derivatives of phen. However, when phen is substituted with functional groups, such as -OH and NH2, that are able to form conventional hydrogen bonds, the dispersion and electrostatic contributions become equivalent and the charge transfer and polarization terms still determine the result. Finally, in the study of metal complexes containing phen, the interaction energy with DNA is more important than in the study of the non-coordinated phen ligand. The other ligands in the complexes can also play an important role by increasing the number of weak interactions with the environment and thus reinforcing the interaction energy.
1,10-phenanthroline (phen) is a heterocycle consisting of three fused rings, with two pyridines fused on a central benzene. The two nitrogen atoms can bind metals using their lone pairs and make it a strong donor. The extended pi system confers to phen the possibility of acting as a pi-acceptor, strengthening the metal-ligand bond. Organometallic complexes of Mo(IV), [Mo(C5H5)2(phen)][PF6]2 (1), and Mo(II), [Mo(C3H5)Br(CO)2(phen)] (2), have been synthesized and characterized, and many aspects of their chemistry studied. The versatility of phen is well reflected in its functionalization, either by replacing hydrogen atoms by other groups, or by extending the frame to 1,10 phenanthroline-5,6-dione or dipyridophenazine. In all these molecules, the pi electrons of the rings and the substituents may interact with their surroundings by weak interactions, namely with biological molecules (DNA duplexes, G-quadruplexes or proteins), opening the way to therapeutic purposes and medical applications. Complex 2 has displayed high cytotoxic activity towards human cancer cell lines, with IC50 below 5 microM for HeLa. DFT calculations have been performed to understand the nature of the interactions responsible for this effect using different kinds of models and analyzing the results in several ways. It was found that for the phen ligand alone the nature of the interaction with two pairs of bases is mainly ruled by dispersion forces although these cannot by themselves balance the repulsive Pauli interaction. Charge transfer, polarization terms and, specially, the electrostatic contribution, become crucial to produce an attractive interaction. This behavior is followed by methylated and ketonic derivatives of phen. However, when phen is substituted with functional groups, such as -OH and NH2, that are able to form conventional hydrogen bonds, the dispersion and electrostatic contributions become equivalent and the charge transfer and polarization terms still determine the result. Finally, in the study of metal complexes containing phen, the interaction energy with DNA is more important than in the study of the non-coordinated phen ligand. The other ligands in the complexes can also play an important role by increasing the number of weak interactions with the environment and thus reinforcing the interaction energy.