The thermal isomerization of the GFP chromophore: A computational study

Abstract

We present a density functional theory (B3LYP) study of the isomerization of 4-hydroxybenzylidene-1,2-dimethyl-imidazolinone (HOBDI), which is to mimic the green fluorescent protein (GFP) chromophore, in the ground state promoted by a nucleophile. Four solvents with different polarity, water, DMSO, methanol, and benzene, have been used to characterize the nucleophile assisted mechanism. The former three solvents have been used as nucleophile to participate in the reaction, while in benzene, we use n-propylamine as the nucleophile. When water, methanol and n-propylamine are used as nucleophile, the isomerization is characterized as a three-step process and the addition of the nucleophile is the rate-determining step. A proton transfer from the nucleophile to the oxygen of imidazolinone (O(1)) is observed during the addition step, which stabilizes the negative charge on O(1) due to the reduction of the C(1)[double bond, length as m-dash]C(2) double bond. The energy barrier to the reaction increases in the order of CH(3)OH <or= water < n-propylamine, which is consistent with the experimental data. Whereas in DMSO, the calculations predict a one-step reaction for the isomerization starting from the zwitterionic state with a high barrier of 26.8 kcal mol(-1), in accord with the slow reaction observed experimentally. Our study suggests that the ability of a nucleophile to assist the thermal isomerization of HOBDI mainly depends on its ability to give a proton upon the addition of the nucleophile to the substrate.

Interfacing the GROMOS (bio)molecular simulation software to quantum‐chemical program packages

“…As evident from a comparison of the left and right panels of Figure 6, the SPC solvent molecules are oriented such that the oxygen points towards the C2 atom of HOBDI which is in accordance with its nucleophilic character, see also Ref. [53].…”

Crystal structure and spectral studies of green fluorescent protein (GFP) chromophore analogue ethyl 2-[(4Z)-(6-hydroxy naphthalen-2-yl) methylene)-2-methyl-5-oxo-4,5-di hydro-1H-imidazol-1-yl] acetate

“…[11][12][13]. Although, majority of the literature suggests that GFP chromophore and its analogues exhibit high fluorescence due to the tautomerization as well as restricted Z-conformation (Scheme 1) of benzylidene imidazolinone (BI) moiety and it undergo excited state E-Z twisting in solutions that triggers internal conversion making them weakly emissive [14,15].…”

Study of Model Systems for Bilirubin and Bilin Chromophores: Determination and Modification of Thermal and Photochemical Properties

“…The study of model systems of photoswitchable biological chromophores is an approach extensively applied to understand the properties of the natural analogues. For instance, the penta-2,4-dieniminium cation and 4-(4-hydroxybenzylidene)-1,2-dimethyl-1 H -imidazol-5­(4 H )-one have been used in numerous studies as model systems of the retinal , and the GFP chromophores, − respectively. Concerning the phytochrome chromophore and bilirubin, dipyrrinone , and benzalpyrrolinone , derivatives (see Figure ) are the most studied models.…”