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

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)₃FeMo₆O₁₈{(OCH₂)₃CNHCOC₆H₅}₂] ? 3.5 ACN ( TBA‐FeMo₆‐bzn ; TBA=tetrabutylammonium, ACN=acetonitrile, bzn=TRIS‐benzoic acid alkanolamide, TRIS?R=(HOCH₂)₃C?R)), (TBA)₃FeMo₆O₁₈{(OCH₂)₃CNHCOC₈H₇}₂] ? 2.5 ACN ( TBA‐FeMo₆‐cin ; cin=TRIS‐cinnamic acid alkanolamide), (TBA)₃MnMo₆O₁₈{(OCH₂)₃CNHCOC₆H₅}₂] ? 3.5 ACN ( TBA‐MnMo₆‐bzn ), and (TBA)₃MnMo₆O₁₈{(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 Na₃FeMo₆O₁₈{(OCH₂)₃CNHCOC₆H₅}₂] ( Na‐FeMo₆‐bzn ), Na₃FeMo₆O₁₈{(OCH₂)₃CNHCOC₈H₇}₂] ( Na‐FeMo₆‐cin ), Na₃MnMo₆O₁₈{(OCH₂)₃CNHCOC₆H₅}₂] ( Na‐MnMo₆‐bzn ), and Na₃MnMo₆O₁₈{(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.