title: A Joint Theoretical and Experimental Study of the Behavior of the DIDS Inhibitor and its Derivatives.
abstract: 4,4'-Diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) is a well-known ion-exchange inhibitor targeting cardiac functions and indirectly impeding both radio- and chemo-resistance. A joint computational and experimental study is presented to provide deeper insights into DIDS and other members of this family of compounds. To this end, we applied state-of-the-art density functional theory (DFT) and time-dependent DFT methods, in addition to measuring the optical properties. The experimental data show that such compounds are highly sensitive to their environment and that the optical properties change within as little time as 7 h. However, the optical properties of DIDS are similar in various acidic/basic environments, which were confirmed by pKa computations on both cis and trans isomers. The protonation analysis also highlights that the singly protonated form of DIDS behaves like a proton sponge compound. The experimentally observed redshift that can be seen when going from water to DMSO was reproduced solely by using the solvation model based on density, although the polarization continuum model and implicit/explicit hybrid schemes were also tested. The characteristic broadening of the absorption peak in water and the vibronic fine structure in DMSO were also reproduced thanks to vibronic coupling simulations associated with the solvent reorganization energy. For other stilbene derivatives, a correlation is found between the maximum absorption wavelength and the Hammett parameters.
authors.affiliation: Laboratoire CEISAM-UMR CNR 6230, Université de Nantes, 2 Rue de la Houssinière, BP 92208, 44322, Nantes Cedex 3, France.
authors.forename: Titouan
authors.initials: T
authors.lastname: Jaunet-Lahary
authors.affiliation: Laboratoire CEISAM-UMR CNR 6230, Université de Nantes, 2 Rue de la Houssinière, BP 92208, 44322, Nantes Cedex 3, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Goupille
authors.affiliation: Laboratoire CEISAM-UMR CNR 6230, Université de Nantes, 2 Rue de la Houssinière, BP 92208, 44322, Nantes Cedex 3, France.|Institut Universitaire de France, 1, rue Descartes, 75005, Paris Cedex 05, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Jacquemin
authors.affiliation: Laboratoire UFIP-UMR CNR 6286, Université de Nantes, 2 Rue de la Houssinière, BP 92208, 44322, Nantes Cedex 3, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Fleury
authors.affiliation: Laboratoire CEISAM-UMR CNR 6230, Université de Nantes, 2 Rue de la Houssinière, BP 92208, 44322, Nantes Cedex 3, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Graton
authors.affiliation: Laboratoire CEISAM-UMR CNR 6230, Université de Nantes, 2 Rue de la Houssinière, BP 92208, 44322, Nantes Cedex 3, France. adele.laurent@univ-nantes.fr.
authors.forename: Adèle D
authors.initials: AD
authors.lastname: Laurent
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000031:analogs & derivatives / Q000737:chemistry*; D007536:Isomerism; D008958:Models, Molecular; D011522:Protons; D011789:Quantum Theory; D013053:Spectrophotometry; D013816:Thermodynamics
chemical_list: D011522:Protons; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
keywords: UV/Vis spectroscopy; density functional calculations; solvent reorganization; stilbene sulfonic acid; vibronic couplings