Quantum chemical studies of the electronic structures of anti-tumor agents: (AuL)-L-III+ (L = porphine, tetraphenylporphyrin)

GoldIII meso-tetraphenylporphyrin complexes are reported as one of potential anti-tumor drugs. Elucidation of the molecular properties and intermolecular interaction with amino acids are crucial in understanding their structure-function relationship and anti-tumor mechanism. In this study, we report quantum-chemical studies on the geometries, electronic structures, chemical bonding, and substituent effect of goldIII porphine cation and GoldIII meso-tetraphenylporphyrin cation (AuTPP+). The stability of square planar D4h goldIII porphine cation primarily originates from the overlap between Au 5dx2_y2 and the ligand group orbitals of the nitrogen atoms of porphine. The electronic effect and the peripheral steric hindrance of the substituents present a combined influence on the geometry of the porphyrin core. Strong electron-donating group would prefer saddling distortion, while sterically hindered groups tend to cause ruffling distortion. The molecular-orbital (MO) energies of mesosubstituted goldIII porphine generally increase from electron-withdrawing to electron-donating substituents, providing opportunity to tune the electronic properties of this kind of promising drugs. Through comprehensive screening of the interaction between AuTPP+ and various amino acids, we find dative interaction as well as potential 7C-7C stacking dominant for AuTPP+ binding with amino acids. In particular, nitrogen atom of unprotonated histidine has been found to have a non-negligible dative bonding interaction with the central gold atom, which might be relevant to the anti-tumor functionality of AuTPP+.