Antitumor activity of bent metallocenes: electronic structure analysis using DFT computations.

Area of Science:

• Computational Chemistry
• Inorganic Chemistry
• Medicinal Chemistry

Background:

• Bent metallocenes are organometallic compounds with potential biological applications.
• Understanding their interaction with DNA nucleotides is crucial for developing new anticancer agents.

Purpose of the Study:

• To investigate the antitumor activities of bent metallocenes ([Cp-M-Cp](2+)) complexed with nucleotides.
• To elucidate the electronic structure basis for the stability and reactivity of these complexes.

Main Methods:

• Density Functional Theory (DFT/BP86) calculations were employed.
• Electronic structure, Walsh energy, and fragment analyses were performed.
• Interaction energies between metallocenes and nucleotides were computed.

Main Results:

• Bent metallocene-nucleotide interactions depend on the stability of hydrolyzed metallocene species.
• Adenine and guanine exhibit stronger binding with bent metallocenes compared to thymine and cytosine.
• Second-row transition metal metallocenes show enhanced binding with pyrimidine-base nucleotides.
• Lewis acidity of metallocenes contributes to strong nucleotide interactions.

Conclusions:

• Antitumor activity is directly proportional to the binding strength between bent metallocenes and nucleotide adducts.
• Computed interaction energies accurately predict experimentally observed antitumor activities.
• Electronic structure and stability analyses provide insights into the mechanism of action.