Реферат: The synthesis and characterization of a lipidlike electrostatic spin probe, (S)-2,3-bis(palmitoyloxy)propyl 2-((4-(4-(dimethylamino)-2-ethyl-1-oxyl-5,5-dimethyl-2,5-dihy- dro-1H-imidaz ol-2-yl) benzyl) disulfanyl) ethyl phosphate (IKMTSL-PTE), are being reported. The intrinsic pK of IKMTSL-PTE was determined by X-band (9.5 GHz) electron paramagnetic resonance (EPR) titration of a water-soluble model compound, 4- (dimethylamino)-2-ethy1-2- (4-(((2hydroxyethyl) disulfanyOrnethyl)phenyl)-5,5- dimethy1-2,5-dihydro -1H-itnidaz ol- 1- oxyl (IKMTSL-ME), an adduct of methanethiosulfonate spin label IKMTSL and 2-mercaptoethanol. The pK(a)(0) of IKMTSL-ME in bulk aqueous solutions was found to be significantly higher than that of 4-(((2-hydroxyethyl)disulfanyl)methyl)-2,2,3,5,5-pentamethylimidazolidin-loxyl (IMTSL-ME), an adduct of the corresponding methanethiosulfonate spin label IMTSL and 2-mercaptoethanol (17 degrees C, pK(a)(0) = 6.16 +/- 0.03 vs 20 degrees C, pK(a)(0)= 3.33 +/- 0.03, respectively). A series of EPR titration experiments with IKMTSL-ME in aqueous solutions containing 0-60% v/v isopropanol have been carried out at 17 and 48 degrees C to determine the effects of temperature and bulk dielectric permittivity constant, c, on the probe pKa. A linear relationship between the probe pK(a) and e has been established and found to be essentially the same at 17 and 48 degrees C. The polarity term contributing to the pK(a) of IKMTSL-PTE at an uncharged lipidlike interface was determined by incorporating the probe into electrically neutral micelles formed from nonionic detergent Triton X-100, and it was found, similar to IMTSL-PTE, to be negative. In negatively charged DMPG lipid bilayers, IKMTSL-PTE exhibits ionization transitions with significantly higher pK(a) values than those previously reported for IMTSL-PTE (e.g., at 17 degrees C, pK(a)(1) = 7.80 +/- 0.03 vs pK(0)(a) = 5.70 +/- 0.05). The surface electrostatic potentials of DMPG lipid bilayers calculated using IKMTSL-PTE titration data were found to be somewhat lower than those calculated using IMTSL-PTE. The lower values measured by IKMTSL-PTE are the likely consequences of the structure of the linker that positions the reporter nitroxide further away from the bilayer plane into aqueous phase. Overall, the ionization transitions of IKMTSL-PTE with plc values close to the neutral pH range make this lipidlike molecule a valuable spectroscopic EPR probe for studying the electrostatic phenomena at biological interfaces, including lipid bilayer/membrane protein systems, that could be unstable in the acidic pH range accessible by the previously available probes.

Библиографическая ссылка: Voinov M.A. , Scheid C.T. , Kirilyuk I.A. , Trofimov D.G. , Smirnov A.I.
IKMTSL-PTE, a Phospholipid-Based EPR Probe for Surface Electrostatic Potential of Biological Interfaces at Neutral pH: Effects of Temperature and Effective Dielectric Constant of the Solvent
Journal of Physical Chemistry B. 2017. V.121. N11. P.2443-2453. DOI: 10.1021/acs.jpcb.7b00592 WOS Scopus РИНЦ

Даты:

Опубликована online:	10 мар. 2017 г.
Опубликована в печати:	23 мар. 2017 г.

Идентификаторы:

Web of science	WOS:000397546200007
Scopus	2-s2.0-85019166335
РИНЦ	31018424
OpenAlex	W2592513582

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