Small molecule interactions with biomacromolecules: selective sensing of human serum albumin by a hexanuclear manganese complex - photophysical and biological studies.
Details
Serval ID
serval:BIB_3EBA3F6E946B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Small molecule interactions with biomacromolecules: selective sensing of human serum albumin by a hexanuclear manganese complex - photophysical and biological studies.
Journal
Journal of materials chemistry. B
ISSN
2050-7518 (Electronic)
ISSN-L
2050-750X
Publication state
Published
Issued date
25/09/2024
Peer-reviewed
Oui
Volume
12
Number
37
Pages
9408-9419
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
A covalently bonded hexanuclear neutral complex, [Mn <sub>6</sub> (μ <sub>3</sub> -O) <sub>2</sub> (3-MeO-salox) <sub>6</sub> (OAc) <sub>2</sub> (H <sub>2</sub> O) <sub>4</sub> ] (1), has been synthesized and characterized by single crystal X-ray diffraction analysis along with IR and HRMS studies. Complex 1 has been found to selectively interact with human serum albumin (HSA), a model transport protein. The interaction of 1 with HSA was investigated by monitoring the change in the absorbance value of HSA at λ = 280 nm with increasing concentration of 1. Likewise, fluorescence titrations were carried out under two conditions: (i) titration of a 5 μM solution of complex 1 with the gradual addition of HSA, showing a ∼9-fold fluorescence intensity enhancement at 424 nm, upon excitation at 300 nm; and (ii) upon excitation at 295 nm, titration of 5 μM HSA solution with the incremental addition of complex 1, showing a quenching of fluorescence intensity at 334 nm, with simultaneous development of a new emission band at 424 nm. A linear form of the Stern-Volmer equation gives K <sub>SV</sub> = 9.77 × 10 <sup>4</sup> M <sup>-1</sup> and the Benesi-Hildebrand plot yields the binding constant as K <sub>BH</sub> = 1.98 × 10 <sup>5</sup> M <sup>-1</sup> at 298 K. The thermodynamic parameters, ΔS°, ΔH°, and ΔG°, were estimated by using the van't Hoff relationship which infer the major contribution of hydrophobic interactions between HSA and 1. It was observed that quenching of HSA emission arises mainly through a dynamic quenching mechanism as indicated by the dependence of average lifetime 〈τ〉 on the concentration of 1. The changes in the CD (circular dichroism) spectral pattern of HSA in the presence of 1 clearly establish the variation of HSA secondary structure on interaction with 1. The most probable interaction region in HSA for 1 was determined from molecular docking studies which establish the preferential trapping of 1 in the subdomain IIA of site I in HSA and substantiated by the results of site-specific marker studies. Complex 1 was further evaluated for its antiproliferative effects in lung cancer A549 cells, which strictly inhibits the growth of the cells in both 2D and 3D mammospheres, indicating its potential application as an anticancer drug.
Keywords
Humans, Serum Albumin, Human/chemistry, Serum Albumin, Human/metabolism, Coordination Complexes/chemistry, Coordination Complexes/chemical synthesis, Coordination Complexes/pharmacology, Manganese/chemistry, Antineoplastic Agents/pharmacology, Antineoplastic Agents/chemistry, Molecular Structure, Small Molecule Libraries/chemistry, Small Molecule Libraries/pharmacology, Small Molecule Libraries/chemical synthesis, Cell Proliferation/drug effects
Pubmed
Web of science
Create date
30/08/2024 16:48
Last modification date
01/10/2024 7:07