Université Paul Sabatier - Bat. 3R1b4 - 118 route de Narbonne 31062 Toulouse Cedex 09, France


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Accueil > Emplois & stages > Sujets de master > DFT insights into the photorelease mechanism of biologically active ligands

DFT insights into the photorelease mechanism of biologically active ligands

LABORATORY : LCPQ, universite Toulouse 3 ; director Thierry Leininger
LABORATORY WEBSITE : http://www.lcpq.ups-tlse.fr/spip.php?rubrique23
INTERNSHIP SUPERVISORS : Isabelle Dixon and Fabienne Alary ; 05.61.55.64.88 ; 05.61.55.69.48 dixon@irsamc.ups-tlse.fr ; alary@irsamc.ups-tlse.fr

INTERNSHIP PROPOSAL : DFT insights into the photorelease mechanism of biologically active ligands

Photoactivated chemotherapy (PACT) consists in the light-triggered delivery of a biologically active molecule to a tumour.[1] Metal complexes are often used in this purpose. The metallic part can either be biologically active or can act as drug carrier.[2] In this latter field, Bonnet’s group has recently reported the controlled photorelease of various ligands from Ru(II) prodrugs, among which sulfur ligands,[3] imine ligands,[4] or amino acids.[5] In joint experimental-theoretical studies, we have shown that the topology of the lowest triplet excited potential energy surface (3PES) was crucial in the ligand photorelease efficiency. In particular, different types of original excited states of metal-centred nature were proposed to be key to the photorelease mechanisms.[6,7,8] Nonetheless, recent results published by Bonnet et al.[5] (Figure 1) point to a subtle combination of various experimental conditions, including fine solvent effects and oxygen : apart from ligand photorelease, Δ/Λ racemization and ligand oxidation have been evidenced, based on various spectroscopic techniques. Rationalizing photorelease efficiencies thus remains a tremendous challenge in these systems.
In this context, we are willing to pursue this collaboration by exploiting a variety of DFT-based methods, allowing us to establish the topology of the lowest 3PES and to get some insight into photorelease mechanisms and possible competitive pathways. This internship will be devoted to the DFT optimization of singlet (ground state) and triplet (excited state) minima and of singlet/triplet minimum energy crossing points ; to the optimization of minimum energy paths along the 3PES ; to the inclusion of solvents effects through various solvation models. TDDFT will also be used to model absorption spectra and to probe the topology of the 1PES and 3PES in singlet/triplet crossing regions.

References
1. N.J. Farrer, L. Salassa, P.J. Sadler, Dalton Trans. 2009, 10690 ; U. Schatzschneider, Eur. J. Inorg. Chem. 2010, 1451.
2. C. Mari, V. Pierroz, S. Ferrari, G. Gasser, Chem. Sci. 2015, 5, 2660 ; J.D. Knoll, C. Turro, Coord. Chem. Rev. 2015, 282-283, 110.
3. R.E. Goldbach, I. Rodriguez-Garcia, J.H. van Lenthe, M.A. Siegler, S. Bonnet, Chem. Eur. J. 2011, 17, 9924 ; V.H.S. van Rixel, A. Busemann, A.J. Göttle, S. Bonnet, J. Inorg. Biochem. 2015, 150, 174 ; V.H.S. van Rixel, B. Siewert, S.L. Hopkins, S.H.C. Askes, A. Busemann, M.A. Siegler, S. Bonnet, Chem. Sci. 2016, 7, 4922.
4. J.-A. Cuello-Garibo, M.S. Meijer, S. Bonnet, Chem. Commun. 2017, 53, 6768.
5. J.-A. Cuello-Garibo, E. Perez-Gallent, L. van der Boon, M.A. Siegler, S. Bonnet, Inorg. Chem. 2017, 56, 4818.
6. A.J. Göttle, F. Alary, M. Boggio-Pasqua, I.M. Dixon, J.-L. Heully, A. Bahreman, S.H.C. Askes, S. Bonnet, Inorg. Chem. 2016, 55, 4448.
7. I.M. Dixon, J.-L. Heully, F. Alary, P.I.P. Elliott, Phys. Chem. Chem. Phys. 2017, 19, 27765.
8. A. Soupart, F. Alary, J.-L. Heully, P.I.P. Elliott, I.M. Dixon, Inorg. Chem. 2018, 57, 3192.

KEY DATE : internship starting 06 Jan. 2020