The Synthesis and Characterization of Aromatic Hybrid Anderson–Evans POMs and their Serum Albumin Interactions: The Shift from Polar to Hydrophobic Interactions

Abstract

Four aromatic hybrid Anderson polyoxomolybdates with Fe3+ or Mn3+ as the central heteroatom have been synthesized by using a pre-functionalization protocol and characterized by using single-crystal X-ray diffraction, FTIR, ESI-MS, 1H NMR spectroscopy, and elemental analysis. Structural analysis revealed the formation of (TBA)3[FeMo6O18{(OCH2)3CNHCOC6H5}2]⋅3.5 ACN (TBA-FeMo6-bzn; TBA=tetrabutylammonium, ACN=acetonitrile, bzn=TRIS-benzoic acid alkanolamide, TRIS–R=(HOCH2)3C–R)), (TBA)3[FeMo6O18{(OCH2)3CNHCOC8H7}2]⋅2.5 ACN (TBA-FeMo6-cin; cin=TRIS-cinnamic acid alkanolamide), (TBA)3[MnMo6O18{(OCH2)3CNHCOC6H5}2]⋅3.5 ACN (TBA-MnMo6-bzn), and (TBA)3[MnMo6O18{(OCH2)3CNHCOC8H7}2]⋅2.5 ACN (TBA-MnMo6-cin). To make these four compounds applicable in biological systems, an ion exchange was performed that gave the water-soluble (up to 80 mm) sodium salts Na3[FeMo6O18{(OCH2)3CNHCOC6H5}2] (Na-FeMo6-bzn), Na3[FeMo6O18{(OCH2)3CNHCOC8H7}2] (Na-FeMo6-cin), Na3[MnMo6O18{(OCH2)3CNHCOC6H5}2] (Na-MnMo6-bzn), and Na3[MnMo6O18{(OCH2)3CNHCOC8H7}2] (Na-MnMo6-cin). The hydrolytic stability of the sodium salts was examined by applying ESI-MS in the pH range of 4 to 9. Sodium dodecylsulfate–polyacrylamide gel electrophoresis (SDS-PAGE) showed that human and bovine serum albumin (HSA and BSA) remain intact in solutions that contain up to 100 equivalents of the sodium salts over more than 4 d at 20 °C. Tryptophan (Trp) fluorescence quenching was applied to study the interactions between the sodium salts and HSA and BSA at pH 5.5 and 7.4. The quenching constants were extracted by using Stern–Volmer analysis, which suggested the formation of a 1:1 POM–protein complex in all samples. It is suggested that the aromatic hybrid POM approaches subdomain IIA of HSA and exhibits hydrophobic interactions with its hydrophobic tails, whereas the Anderson core is stabilized through electrostatic interactions with polar amino acid side chains from, for example, subdomain IB.

Synthesis and characterization of hybrid Anderson hexamolybdoaluminates(III) functionalized with indometacin or cinnamic acid

“…Three different coordination modes of O atoms are found in the structure: six triple-bridged O atoms (denoted 3 -O) connect the heteroatom and two Mo atoms, six double-bridged O atoms (denoted 2 -O) connect two Mo atoms and two terminal O atoms (denoted O t ) are connected to each of the six Mo atoms. The bond lengths of the three different binding modes are summarized in Table 2 and are in good agreement with other tris-functionalized Anderson POMos (Wu et al, 2011;Al-Sayed et al, 2015;Blazevic et al, 2015).…”

“…If the R group itself is reactive (-NH 2 , -CH 2 OH etc. ), post-functionalization with a variety of organic mol-ecules, including ligands containing aromatic units (Al-Sayed et al, 2015) or alkyl chains (Rosnes et al, 2013) via imine, amide or ester-bond formation, is possible. The resulting hybrid materials were used in supramolecular self-assembly (Macdonell et al, 2015) or for the formation of metal-organic frameworks (MOFs; Li et al, 2016).…”

Polyoxometalates: more than a phasing tool in protein crystallography

“…Under these circumstances, the heteroatom of the Anderson–Evans structure is hardly able to directly interact with the protein, especially the protein’s backbone. This shielding effect was verified for different Anderson–Evans polyoxomolybdates containing partially strong Lewis acids as heteroatom (Fe III Mo 6 , Mn III Mo 6 , Ga III Mo 6 , Cr III Mo 6 ) as none of the tested structures exhibited any hydrolytic activity towards proteins [ 119 , 120 , 128 , 129 ]. Therefore, it seems that the Anderson–Evans archetype is in general one of the safest POM with respect to the preservation of the protein’s integrity, which further strengthens the suitability of this POM-archetype as crystallization agent.…”

Supramolecular assemblies of organo-functionalised hybrid polyoxometalates: from functional building blocks to hierarchical nanomaterials

“…In these studies, the authors prepared a series of Anderson oxoclusters with a range of both mono-and bis-substituted hydrophilic ligands (e.g. -NH 3+ or -OH terminated tris-bases), 223 and bis-substituted hydrophobic ligands (phenyl-or cinnamic acid-terminated groups), 224 and studied their stability under biologically relevant aqueous conditions in the presence of the relevant protein. In both cases, the oxoclusters showed excellent stability in a pH range of 4 to 9 and, critically, showed no hydrolytic reactivity towards the serum albumin proteins.…”