Effect of the Heteroaromatic Antenna on the Binding of Chiral Eu(III) Complexes to Bovine Serum Albumin

Abstract

The cationic enantiopure ( R,R ) and luminescent Eu(III) complex [Eu(b iso Qcd)(H 2 O) 2 ] OTf (with b iso Qcd = N,N′ -bis(2- iso quinolinmethyl)- trans -1,2-diaminocyclohexane N,N′ -diacetate and OTf = triflate) was synthesized and characterized. At physiological pH, the 1:1 [Eu(b iso Qcd)(H 2 O) 2 ] + species, possessing two water molecules in the inner coordination sphere, is largely dominant. The interaction with bovine serum albumin (BSA) was studied by means of several experimental techniques, such as luminescence spectroscopy, isothermal titration calorimetry (ITC), molecular docking (MD), and molecular dynamics simulations (MDS). In this direction, a ligand competition study was also performed by using three clinically established drugs (i.e., ibuprofen, warfarin, and digitoxin). The nature of this interaction is strongly affected by the type of the involved heteroaromatic antenna in the Eu(III) complexes. In fact, the presence of iso quinoline rings drives the corresponding complex toward the protein superficial area containing the tryptophan residue 134 (Trp134). As the main consequence, the metal center undergoes the loss of one water molecule upon interaction with the side chain of a glutamic acid residue. On the other hand, the similar complex containing pyridine rings ([Eu(bpcd)(H 2 O) 2 ]Cl with bpcd = N,N′ -bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane N,N′ -diacetate) interacts more weakly with the protein in a different superficial cavity, without losing the coordinated water molecules.

Water-Soluble Dioxidovanadium(V) Complexes of Aroylhydrazones: DNA/BSA Interactions, Hydrophobicity, and Cell-Selective Anticancer Potential

“…It is also the most extensively studied protein due to its importance in physiological and pharmacological functions. It is advantageous to study serum albumin, as the limited number of binding sites with high specificity plays a pivotal role in the transportation and delivery of different endogenous and exogenous species . Bovine serum albumin (BSA), having a 76% sequence homology for human serum albumins (HSA), has been broadly studied, as it is the most abundant model protein of blood plasma. , From literature reports, it has been observed that vanadium complexes showing higher DNA and protein binding ability exhibited better cytotoxicity, and so the assessment of this ability is an important aspect prior to anticancer studies, ,,,− but the involvement of several other mechanisms of cellular activity may also be possible. − In some reports, the cellular cytotoxicity activity of transition-metal complexes (V and Cu) follows a mechanism of action different from DNA and protein interactions. − Possibly, the increased electron density in the aromatic ring systems, aqueous solubility, membrane permeability, or specific hydrophobic interactions in target binding pockets lead to an increase in cytotoxicity. ,− In this context, due to hydrophobicity, enhancement in the bioavailability of a drug by its internalization to the target cells and ability to reach the site of action is another point of interest. , Thus, in this work, we have sought to correlate the behavior of complexes in aqueous stability, hydrophobicity, DNA/protein interactions related to their cytotoxicity.…”

Lifetime Multiplexing with Lanthanide Complexes for Luminescence In Situ Hybridisation

“…The non‐radiative decay rate is found to be larger for Tc (9.52 ms −1 ) in comparison to DTBTA (0.69 ms −1 ) and BHHCT (1.45 ms −1 ), which can be attributed to its weak shielding of the Eu centre against the solvent molecules. Consequently, Tc−Eu has shortest τ obs among the three complexes alongside lowest luminescence brightness (indicated by ϵ×φ Ln ); however, the latter can be improved when Tc binds to serum albumin, as reported previously [44–45] . It should be noted that the solvent also affects the photophysical properties including the lifetime, due to potential changes in refractive index, pH, and coordination to the lanthanide ion.…”

Lanthanide‐Based Complexes Containing a Chiral trans‐1,2‐Diaminocyclohexane (DACH) Backbone: Spectroscopic Properties and Potential Applications

“…The interaction among bovine serum albumin (BSA) and two DACH‐based Eu(III) complexes was studied by means of several experimental techniques [53] . Interestingly, we demonstrated that the nature of this interaction is strongly affected by the type of the involved heteroaromatic antenna in the Eu(III) complexes.…”

“…In the latter applications, the formation of ternary ML‐analyte species is monitored at fixed conditions (most often physiological pH and ionic medium) and conditional formation constants are determined. A variety of methods have been employed, such as fluorimetry, spectrophotometry, NMR, and calorimetric titrations [52–54] . In some cases, [53] the combination of different techniques and computational methods is necessary to distinguish between different speciation models ( vide infra ).…”

“…A variety of methods have been employed, such as fluorimetry, spectrophotometry, NMR, and calorimetric titrations [52–54] . In some cases, [53] the combination of different techniques and computational methods is necessary to distinguish between different speciation models ( vide infra ).…”