TY  - JOUR
AU  - Petrović, Predrag
AU  - Grimme, Stefan
AU  - Zarić, Snežana D.
AU  - Pfeffer, Michel
AU  - Đukić, Jean-Pierre
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1806
AB  - Self-aggregation in water of anti-cancer agents such as oxaliplatin (1) or its palladium-containing parent (2) is suspected to be the main reason for the exceptional resistance of concentrated infusions of these complexes to hydrolysis; this hypothesis, i.e. the self-association of metal chelates, was investigated in a systematic manner by experimental and theoretical means. H-1 diffusion-ordered NMR spectroscopy (DOSY NMR) and UV-visible absorption titration were inconclusive as to the formation of a dimer of 1 in water or DMSO. Further isothermal titration calorimetry (ITC) methods allowed the accurate determination of the enthalpy of formation of only the homodimer [2](2) and putative heterodimer [1.2] together with an estimation of the formation constants, which indicate that dimer formation is not a spontaneous process in solution, whereas electrospray ESI mass spectroscopy tends to suggest the contrary in the gas phase. A dispersion-corrected DFT method, i. e. DFT-D (BLYP-D3), was used to model the aggregation in solution (COSMO) and to investigate the assisting role of London force in the cohesion of bimolecular aggregates. The concordance of experimental and theoretical thermodynamic parameters was judged reasonably even though the treatment of solvation by conventional continuum models does not account for specific interactions of the solute with molecules of solvent; nonetheless these results outline the importance of dispersion, a.k.a. London force. The role of the latter was further stressed by computing the affinities of 1 and 2 for the lipophilic cavity of cucurbit[7]uril in modeled water (COSMO-RS), which were preliminarily determined experimentally by ITC methods using pure water as solvent. From our investigations carried out in pure water the connection between the notorious chemical stability of "concentrated'' infusions of 1 in aqueous media and the formation of oligomers remains unsettled.
PB  - Royal Soc Chemistry, Cambridge
T2  - Physical Chemistry Chemical Physics
T1  - Experimental and theoretical investigations of the self-association of oxaliplatin
VL  - 16
IS  - 28
SP  - 14688
EP  - 14698
DO  - 10.1039/c4cp01500b
ER  - 

@article{
author = "Petrović, Predrag and Grimme, Stefan and Zarić, Snežana D. and Pfeffer, Michel and Đukić, Jean-Pierre",
year = "2014",
abstract = "Self-aggregation in water of anti-cancer agents such as oxaliplatin (1) or its palladium-containing parent (2) is suspected to be the main reason for the exceptional resistance of concentrated infusions of these complexes to hydrolysis; this hypothesis, i.e. the self-association of metal chelates, was investigated in a systematic manner by experimental and theoretical means. H-1 diffusion-ordered NMR spectroscopy (DOSY NMR) and UV-visible absorption titration were inconclusive as to the formation of a dimer of 1 in water or DMSO. Further isothermal titration calorimetry (ITC) methods allowed the accurate determination of the enthalpy of formation of only the homodimer [2](2) and putative heterodimer [1.2] together with an estimation of the formation constants, which indicate that dimer formation is not a spontaneous process in solution, whereas electrospray ESI mass spectroscopy tends to suggest the contrary in the gas phase. A dispersion-corrected DFT method, i. e. DFT-D (BLYP-D3), was used to model the aggregation in solution (COSMO) and to investigate the assisting role of London force in the cohesion of bimolecular aggregates. The concordance of experimental and theoretical thermodynamic parameters was judged reasonably even though the treatment of solvation by conventional continuum models does not account for specific interactions of the solute with molecules of solvent; nonetheless these results outline the importance of dispersion, a.k.a. London force. The role of the latter was further stressed by computing the affinities of 1 and 2 for the lipophilic cavity of cucurbit[7]uril in modeled water (COSMO-RS), which were preliminarily determined experimentally by ITC methods using pure water as solvent. From our investigations carried out in pure water the connection between the notorious chemical stability of "concentrated'' infusions of 1 in aqueous media and the formation of oligomers remains unsettled.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Physical Chemistry Chemical Physics",
title = "Experimental and theoretical investigations of the self-association of oxaliplatin",
volume = "16",
number = "28",
pages = "14688-14698",
doi = "10.1039/c4cp01500b"
}

Petrović, P., Grimme, S., Zarić, S. D., Pfeffer, M.,& Đukić, J.. (2014). Experimental and theoretical investigations of the self-association of oxaliplatin. in Physical Chemistry Chemical Physics
Royal Soc Chemistry, Cambridge., 16(28), 14688-14698.
https://doi.org/10.1039/c4cp01500b

Petrović P, Grimme S, Zarić SD, Pfeffer M, Đukić J. Experimental and theoretical investigations of the self-association of oxaliplatin. in Physical Chemistry Chemical Physics. 2014;16(28):14688-14698.
doi:10.1039/c4cp01500b .

Petrović, Predrag, Grimme, Stefan, Zarić, Snežana D., Pfeffer, Michel, Đukić, Jean-Pierre, "Experimental and theoretical investigations of the self-association of oxaliplatin" in Physical Chemistry Chemical Physics, 16, no. 28 (2014):14688-14698,
https://doi.org/10.1039/c4cp01500b . .