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

Abstract

The antitumor activities of bent metallocenes [Cp-M-Cp](2+) (M = Ti, V, Nb, Mo) and complexes of them with guanine, adenine, thymine and cytosine nucleotides have been probed using electronic structure calculations. DFT/BP86 calculations have revealed that the bent metallocene-nucleotide interaction strongly depends on the stability of the hydrolyzed form of the bent metallocene dichloride [Cp(2)M](2+) species, and in turn the stability of the [Cp(2)M](2+) species strongly depends on the electronic structure of [Cp(2)M](2+). Detailed electronic structure and Walsh energy analyses have been carried out for the hydrolyzed forms of four [Cp-M-Cp](2+) (M = Ti, V, Nb, Mo) species to find out why the bent structure is unusually stable. Energy changes that occur during the bending process in frontier molecular orbitals as well as the p(π)-d(π) overlap have been invoked to account for the anticipated antitumor activities of these species. The bonding situation and the interactions in bent metallocene-nucleotide adducts were elucidated by fragment analysis. Of the four nucleotides complexed with the four bent metallocenes, adenine and guanine show better binding abilities than the other two nucleotides. Metallocenes of second-row transition metals exhibit better binding with pyrimidine-base nucleotides. In particular, the Lewis acidic bent metallocenes interact strongly with nucleotides. The antitumor activity is directly related to the binding strength of the bent metallocene with nucleotide adducts, and the computed interaction energy values correlate very well with the experimentally observed antitumor activities.

A Theoretical Study on Interaction of Cyclopentadienyl Ligand with Alkali and Alkaline Earth Metals

“…A vast majority of studies focus on metallocenes which contain transition metals and their derivatives on account of the wide range of their applications. − On the other hand main group metallocenes have the ability to adopt a wide variety of molecular geometries, show a number of interesting bonding types and hapticities and form structurally and chemically divergent group of compounds. − They are among the most commonly used reagents for synthesis of many other types of metallocenes.…”

A Theoretical Investigation on the Oxidation of Carbon Monoxide by an Aqueous Molybdocene

“…Nevertheless, we validated B3LYP results for the particular process under study by performing computations on the rate‐determining energy barrier of the most favorable reaction mechanism (see Results and Discussion) found for the reaction between [Cp 2 Mo(OH)(OH 2 )] + and CO by using the BP86,58,72 M06,73 CAM‐B3LYP,74 and LC‐BLYP75–77 methods. In particular, BP86 has proven to be adequate in studying the geometrical, electronic, and energetic properties of aqueous molybdocenes that are related to their antitumor activity 78. M06 has been selected on account of its good performance in evaluating energy barriers for transition‐metal‐containing systems, whereas the effect of long‐range interactions has been taken into account through the use of CAM‐B3LYP and LC‐BLYP.…”

Homogeneous Organometallic Catalysts for Improved Electrochemical Kinetics of Li–S Batteries

“…For example, Luo et al used density functional theory (DFT) calculations and electrochemical characterizations to study the effect of nickel chloride dimethoxymethane additives as homogeneous catalysts for LiSBs, and they claimed that under lean electrolyte conditions, say E/S ≈ 5, the battery exhibited a stable capacity of 784 mAh g –1 at 0.1 C for 500 cycles . Recently, metallocene-based organometallic compounds with distinct electronic properties, along with a valence electron count and modification of metal–carbon (M–C) bonds, showed incredible catalytic properties in redox-flow batteries (RFB), − olefin polymerization, , anticancer reagents, etc . For example, Ding et al found that the design of Li–RFB with a cobaltocene redox mediator improved the working potential to 1.7 V; in addition, the working potential was increased to 2.1 V when methyl groups were added to the Cp ring, illustrating the possibility of tailoring the properties of metallocene through functionalization .…”