Hydrophilic meso-substituted cyanine dyes in solution and in complexes with serum albumins: spectral properties and mole

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Hydrophilic meso-substituted cyanine dyes in solution and in complexes with serum albumins: spectral properties and molecular docking study PAVEL G PRONKIN*

, LUDMILA A SHVEDOVA and ALEXANDER S TATIKOLOV

N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119334, Russia E-mail: [email protected] MS received 3 July 2020; revised 10 September 2020; accepted 5 October 2020

Abstract. The absorption and fluorescence spectral properties of three meso-substituted hydrophilic thiacarbocyanine dyes were studied in solutions and in noncovalent complexes with human and bovine serum albumins (HSA and BSA, respectively). The presence of alkyl substituents at the meso-position of the polymethine chain of the dyes determines the occurrence of a cis–trans equilibrium. Dyes form aggregates in aqueous media; the effect of electrolyte (NaCl) on aggregation has been studied. The interaction of the dyes with albumins leads to the decomposition of the aggregates and is accompanied by a shift in the isomeric equilibrium. Complexation with HSA leads to accumulation of dye monomers in the trans-form. However, in the case of BSA the cis-to-trans isomeric shift is incomplete. Using the fluorescence data, the effective binding constants of the trans-isomers with albumins (Ka) and the detection limits of albumin molecules (LD and LQ) were determined. The data obtained are indicative of high selectivity of some dyes to HSA compared to BSA. The results of molecular docking experiments correspond to the data obtained from the spectra. The influence of the dyes on intrinsic fluorescence of HSA and BSA was also studied, and fluorescence quenching, static in nature, was detected. Keywords. Polymethine (cyanine) dyes; serum albumins; complexation; cis–trans equilibrium; spectralfluorescent probes; fluorescence growth.

1. Introduction Polymethine (cyanine) dyes, having a superior range of variation of the absorption, fluorescence, and photochemical properties among known organic dyes, are actively studied and applied in various fields.1,2 The presence of a flexible polymethine chain in the structure of their molecules causes low quantum yields of cyanine fluorescence in solutions since the energy dissipation of the excited electronic state of cyanine molecules occurs by nonradiative mechanisms (vibrational relaxation, photoisomerization).3 Meso-substituted thiacarbocyanine dyes are characterized by a polarity-dependent equilibrium between the cis- and trans-isomeric forms.4,5 The ability of cyanine dyes to interact noncovalently with biomacromolecules has been actively

studied.6,7 The formation of complexes with proteins and nucleic acids has a noticeable effect on the absorption and fluorescence properties6–8 and photochemistry of the dyes.9,10 The significant changes in the photophysical and photochemical properties of cyanine dyes upon binding to biomacromolecules make it possible to use them as