Structure–Activity Relationships for the Affinity of Chaotropic Polyoxometalate Anions towards Proteins

Abstract

The influence of the composition of chaotropic polyoxometalate (POM)a nions on their affinity to biological systems was studied by meanso fa tomistic molecular dynamics (MD)s imulations. The variations in the affinity to hen egg-white lysozyme (HEWL) were analyzed along two series of POMs whereby the charge or the size and shape of the metal cluster are modified systematically.O ur simulations revealed aq uadratic relationship between the chargeo ft he POM and its affinity to HEWL as ac onsequence of the parabolic growth of POM···water interaction with the charge. As the chargei ncreases,P OMs becomel essc haotropic (more kosmotropic)i ncreasing the number and the strengtho f POM-water hydrogen bonds and structuringt he solvation shell aroundt he POM. This atomistic description explains the proportionally larger desolvation energies and less protein affinity for highly charged POMs, and consequently,t he preference for moderate charged ensities( q/M = 0.33). Also, our simulations suggest that POM···protein interactions are size-specific. The cationic pockets of HEWL protein show a preference for Keggin-like structures, which display the optimal dimensions ( % 1nm). Finally,w ed eveloped aq uantitative multidimensional model for protein affinity with predictive ability (r 2 = 0.97; q 2 = 0.88) using two molecular descriptors that account for the charge density (charge per metal atom ratio; q/M)a nd the size and shape (shape weightedvolume; V S ).

Polyoxometalates in solution: speciation under spotlight

“…A recent theoretical study by Carbo and co-authors also demonstrates that Keggin anions with lower net charge have higher affinity towards proteins. 249 The selective peptide bond hydrolysis for human serum albumin, oxidized insulin chain B, myoglobin and cytochrome c by a range of Ce(IV)-substituted and Zr(IV)-substituted Lindqvist, Keggin and Wells-Dawson POMs was investigated by Parac-Vogt's group along with speciation in solution detailed in her recent review. 250 For instance, a combination of low-temperature 31 P DOSY NMR spectroscopy and theoretical calculations allowed authors to conclude that in an aqueous solution with pD 6.4 the Keggin-type dimer [{a-P V W VI 11 Zr IV (m-OH)(H 2 O)} 2 ] 8À used as enzyme mimetic for the hydrolysis of the phosphoester bonds in the DNA model substrate BNPP is present in equilibrium with its monomeric form.…”

Hofmeister effect in the Keggin-type polyoxotungstate series

“…One of the most striking supramolecular properties of POMs arises from their ability to form in solution resilient nonbonding contacts with neutral surfaces such as organic macrocycles, micelles, proteins or polymers. [21][22][23][24][25][26][27][28][29][30] Actually, their solution behavior appears "counter-intuitive" because POMs are anionic inorganic discrete species considered generally as hydrophilic. Others and us established that association phenomena between POMs and organic moieties are driven by a solvent mediated effect arising from a water structure recovery upon release of the POM's and the moiety's hydration water.…”

Supramolecular Association between γ-Cyclodextrin and Preyssler-Type Polyoxotungstate

“…The chaotropic character of POMs has now been definitively recognized, and some of them have even been identified as superchaotropic entities according to the Hofmeister classification [ 23 , 24 ]. The strength of these supramolecular host−guest associations can vary considerably depending on the shape, size and most importantly the charge density of the POM [ 23 , 25 ]. Among the large family of POM structures, known examples of complexation with CD include Lindqvist [ 26 ], Keggin [ 23 , 27 ], and Dawson-type POMs [ 22 ].…”