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

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

doi:10.1021/la202882k

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

Chemistry

Research output: Contribution to journal › Article › peer-review

15 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 language	English (US)
Pages (from-to)	939-949
Number of pages	11
Journal	Langmuir
Volume	28
Issue number	1
DOIs	https://doi.org/10.1021/la202882k
State	Published - Jan 10 2012

ASJC Scopus subject areas

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

Access to Document

10.1021/la202882k

Cite this

@article{5cffa25e5bd2417cb3081584480183d3,

title = "Trinuclear ruthenium clusters as bivalent electrochemical probes for ligand-receptor binding interactions",

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.",

author = "Feld, {Daniel J.} and Hsu, {Hsiao Tieh} and Eckermann, {Amanda L.} and Meade, {Thomas J.}",

year = "2012",

month = jan,

day = "10",

doi = "10.1021/la202882k",

language = "English (US)",

volume = "28",

pages = "939--949",

journal = "Langmuir",

issn = "0743-7463",

publisher = "American Chemical Society",

number = "1",

}

TY - JOUR

T1 - Trinuclear ruthenium clusters as bivalent electrochemical probes for ligand-receptor binding interactions

AU - Feld, Daniel J.

AU - Hsu, Hsiao Tieh

AU - Eckermann, Amanda L.

AU - Meade, Thomas J.

PY - 2012/1/10

Y1 - 2012/1/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84855641709&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855641709&partnerID=8YFLogxK

U2 - 10.1021/la202882k

DO - 10.1021/la202882k

M3 - Article

C2 - 22053821

AN - SCOPUS:84855641709

SN - 0743-7463

VL - 28

SP - 939

EP - 949

JO - Langmuir

JF - Langmuir

IS - 1

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this