Trinuclear ruthenium clusters as bivalent electrochemical probes for ligand-receptor binding interactions

Daniel J. Feld, Hsiao Tieh Hsu, Amanda L. Eckermann*, Thomas J. Meade

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Despite their popularity, electrochemical biosensors often suffer from low sensitivity. One possible approach to overcome low sensitivity in protein biosensors is to utilize multivalent ligand-receptor interactions. Controlling the spatial arrangement of ligands on surfaces is another crucial aspect of electrochemical biosensor design. We have synthesized and characterized five biotinylated trinuclear ruthenium clusters as potential new biosensor platforms: [Ru 3O(OAc) 6CO(4-BMP)(py)] 0 (3), [Ru 3O(OAc) 6CO(4-BMP) 2] 0 (4), [Ru 3O(OAc) 6L(4-BMP)(py)] + (8), [Ru 3O(OAc) 6L(4-BMP) 2] + (9), and [Ru 3O(OAc) 6L(py) 2] + (10) (OAc = acetate, 4-BMP = biotin aminomethylpyridine, py = pyridine, L = pyC16SH). HABA/avidin assays and isothermal titration calorimetry were used to evaluate the avidin binding properties of 3 and 4. The binding constants were found to range from (6.5-8.0) × 10 6 M -1. Intermolecular protein binding of 4 in solution was determined by native gel electrophoresis. QM, MM, and MD calculations show the capability for the bivalent cluster, 4, to intramolecularly bind to avidin. Electrochemical measurements in solution of 3a and 4a show shifts in E 1/2 of -58 and -53 mV in the presence of avidin, respectively. Self-assembled monolayers formed with 8-10 were investigated as a model biosensor system. Diluent/cluster ratio and composition were found to have a significant effect on the ability of avidin to adequately bind to the cluster. Complexes 8 and 10 showed negligible changes in E 1/2, while complex 9 showed a shift in E 1/2 of -43 mV upon avidin addition. These results suggest that multivalent interactions can have a positive impact on the sensitivity of electrochemical protein biosensors.

Original languageEnglish (US)
Pages (from-to)939-949
Number of pages11
JournalLangmuir
Volume28
Issue number1
DOIs
StatePublished - Jan 10 2012

ASJC Scopus subject areas

  • Materials Science(all)
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Spectroscopy
  • Electrochemistry

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