Abstract
Luminescence spectroscopy has been used to monitor the selective and reversible binding of pH sensitive, macrocyclic lanthanide complexes, [LnL1], to the serum protein α1-AGP, whose concentration can vary significantly in response to inflammatory processes. On binding α1-AGP, a very strong induced circularly-polarised europium luminescence signal was observed that was of opposite sign for human and bovine variants of α1-AGP - reflecting the differences in the chiral environment of their drug-binding pockets. A mixture of [EuL1] and [TbL1] complexes allowed the ratiometric monitoring of α1-AGP levels in serum. Moreover, competitive displacement of [EuL1] from the protein by certain prescription drugs could be monitored, allowing the determination of drug binding constants. Reversible binding of the sulphonamide arm as a function of pH, led to a change of the coordination environment around the lanthanide ion, from twisted square antiprism (TSAP) to a square antiprismatic geometry (SAP), signalled by emission spectral changes and verified by detailed computations and the fitting of NMR pseudocontact shift data in the sulphonamide bound TSAP structure for the Dy and Eu examples. Such analyses allowed a full definition of the magnetic susceptibility tensor for [DyL1].
Highlights
The acute phase proteins found in human serum play a multitude of roles in vivo
We report a series of new pH-responsive lanthanide complexes [LnL1] (Ln 1⁄4 Y, Eu, Tb, Dy; Fig. 1), which show a pronounced and speciesdependent affinity towards a1-AGP, and a remarkable variation in metal complex helicity in the protein bound form, that is a function of AGP type and of local pH
We reported a europium DO2A-based probe, [EuL2], bearing two azaxanthone chromophores that showed selective binding for both a1-AGP and a1-antitrypsin (a1-AAT) with respect to human serum albumin (Fig. 2).[10,11,12]
Summary
The acute phase proteins found in human serum play a multitude of roles in vivo. Deviations from their normal concentration values can indicate the onset or presence of certain diseases. As a result of competitive binding.[15] As only a very low emission intensity was observed for [EuL1] without any added a1-AGP, the terbium analogue [TbL1] was used to investigate the protonation behaviour of the complex.
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