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Research Fields
Computational enzymology
The study of catalytic and inhibition mechanisms of enzymes of different classes with and without metal ions as cofactor has been performing using QM cluster model. Also QM/MM methodologies are employed with the QM region described at the DFT level with large basis sets embedded in more complete enzyme models described at the MM level.
Molecular dynamics simulations have been using to address main aspects of the enzymatic activity.
Molecular docking studies have been applying with the aim to obtain a most adequate enzyme-substrate complex pose as starting point for the next mechanistic investigation. If it occurs, molecular mechanics parameters for metal enzymes in several ligand environments are developed.
Transition-metal catalysis in nonbiological systems
The discovery of new catalysts for chosen reactions has mainly relied, until recently, on trial and error. This kind of approach is both cost- and time-consuming. Thanks to the increased availability of high-powered computers and user-friendly software packages for electronic structure calculations and the development of new computational approaches, computational chemistry has evolved into a powerful tool that allows the study of complex reaction mechanisms operating in homogeneous catalysis and the origin of various selectivity and reactivity properties at the atomic level. The proper description of a targeted catalytic system can require different kinds of protocol based on different levels of theory. At this purpose valuable insights can still be gained from hybrid computational techniques that allow realizations of extensive reaction pathway analyses.
Although challenges do remain, by the use of computational chemistry tools not only mechanisms of complex reactions can be elucidated, but also experiments for the improvement of synthetic methods can be guided or new catalysts can be rationally designed through meaningful predictions of the structure-reactivity relationship.
Photodynamic Therapy and Photoactivated chemotherapy
Severe side-effects associated with the intake of anticancer drugs are usually a consequence of the lack specificity as drugs kill both cancer and healthy cells. Photodynamic Therapy (PDT) is a very interesting alternative strategy that typically results in fewer side-effects. Indeed, toxic singlet oxygen, which destroys the cancer cells, is produced only in the regions were the light source is applied when a photosensitizer is irradiated with light of appropriate wavelength Nonetheless, the photosensitizers currently on the market have still important drawbacks which include, for example, a lack of selective uptake in cancer cells. Reliance on triplet oxygen (3O2) to produce toxic singlet oxygen (1O2) is the most serious drawback of PDT since tumors are hypoxic. Photoactivated chemotherapy (PACT) uses a combination of light and chemical compounds to induce cell death and, unlike PDT, the presence of oxygen is not required. Computational chemistry offers a unique opportunity in designing new and efficient metal-based PACT agents for the treatment of hypoxic tumors.
Antioxidants
The computational approaches can contribute to gain a deeper knowledge on the molecules offering antioxidant protection. Several reaction mechanisms involved in the protective processes along with the chemical nature of the reacting free radical, the polarity of the environment and the pH in aqueous solution can be taken into account.
Metal complexes in cancer therapy
Cisplatin and its derivatives occupy a prominent position in cancer chemotherapy. To avoid Pt(II) drugs shortcomings, from one side, a large number of compounds belonging to the class of bifunctional platinum has been synthesized and tested on the basis of a consolidated structure activity relationship protocol. On the other side, several alternative strategies based on: ‘non classical’ platinum compounds such as Pt(IV) pro-drugs, monofuctional platinum drugs and non-platinum metal complexes, have been proposed. Computational Chemistry allows us to investigate the mode of action of all these classes of compounds with the possibility to design new candidates as anticancer metal drugs more active and less dangerous than those actually in use.
