Advancing Electrochemical Sensing: The Robust Stability of N-Heterocyclic Carbene Monolayers

Significance 

Self-assembled monolayers (SAMs) are a critical technology for the field of electrochemical sensing.  SAMs allow for the passivation and functionalization of surfaces tuned to provide or enhance specific applications of materials and currently serve as key elements for expanding electrochemical sensing into biological applications. When looking at electrochemical sensing, SAMs on the electrode surface reduce extraneous signal, leading to improved sensitivity and higher signal-to-noise ratios in sensors. Additionally, SAMs allow specific functionalization of the sensor surface with affinity receptors such as aptamers to enhance specificity of electrochemical sensors. Sensors functionalized via SAMs have already been used for the detection of heavy metals in water, glucose in blood, and pollutants in air and soil. Thiols serve as the traditional moieties for SAMs, but they suffer in their stability and robustness, particularly in biological environments.

N-heterocyclic carbenes (NHCs) have recently emerged as a promising alternative to thiol-based SAMs due to their robustness, versatile surface functionality, and superior stability. NHCs possess a lone pair of electrons on the central carbene carbon, which facilitates a strong dative bond with transition metals, allowing for robust passivation and excellent stability on metal surfaces. Surfaces that incorporate NHC monolayers tend to exhibit robustness under various physical and chemical conditions, making them suitable for real-world applications. The chemical structure of NHCs can be readily modified by changing the substituents on the nitrogen atoms or the backbone of the molecule. This tunability allows for the optimization of NHCs for specific applications by altering their electronic properties, steric effects, and interaction with target analytes. When all these traits are applied towards electrochemical sensing, there is a great opportunity towards bringing this technology closer to biomedical implementation. NHCs could improve the stability of the functionalized SAM on the electrode surface, preventing sensor decay over the long-term. Additionally,  tailoring the NHCs can lead to enhanced selectivity and sensitivity of the sensors toward particular compounds.

To this account, in a new study published in ACS Applied Materials & Interfaces by Miguel Aller Pellitero and Professor Netzahualcóyotl (Netz) Arroyo-Currás from the Johns Hopkins University School of Medicine and Isabel Jensen and Professor David Jenkins from the University of Tennessee and Nathaniel Dominique, Lilian Chinenye Ekowo and Jon Camden from the University of Notre Dame, the researchers conducted in-depth exploration of NHCs and their application to forming robust monolayers on gold surfaces for electrochemical sensing. They investigated the electrochemical behavior, self-assembly, and stability of NHC monolayers, juxtaposing the results against traditional thiol-based monolayers.

In their experiments, the team focused on two specific NHC compounds: 1,3-diisopropylbenzimidazole—the ‘standard’ NHC for SAMs studies—and 5-(ethoxycarbonyl)-1,3-diisopropylbenzimidazole, and examined their capacity to form SAMs on gold electrodes from methanolic solutions of their trifluoromethanesulfonate salts. They used advanced electrochemical and surface characterization techniques, including cyclic voltammetry and X-ray photoelectron spectroscopy, to test SAM formation, electrochemical behavior, and stability under continuous voltammetric interrogation. The authors demonstrated that NHC monolayers exhibit comparable surface passivation capabilities to those of mercaptohexanol (MCH) monolayers, a well-known benchmark and standard in thiol-based SAMs. This finding is significant as it highlights the potential of NHCs in forming stable, well-organized monolayers capable of serving as effective barriers against non-specific adsorption and electrochemical noise, which are prevalent challenges in electrochemical biosensing applications.

One of the authors’ key results is the development of baseline evaluation methodology for the behaviors of NHC monolayers under electrochemical cycling, which allows for quantitative investigations towards electrochemical sensing applications. For example, the authors were able to evaluate the performance of NHC monolayers formed via trifluoromethanesulfonate salt deposition in comparison to benchmark thiols. The NHC monolayers in this case demonstrate admirable stability within a specific voltage range but are prone to desorption at voltages beyond this range, both cathodically and anodically, while the thiol monolayers exhibited a broader voltage tolerance before showing desorption. The ability to quantify performance, particularly in areas such as voltage constraints, is vital for the design and optimization of electrochemical sensors that rely on NHC monolayers, for both the further development of NHC monolayers for these applications, as well as ensuring the stability and functionality of electrochemical sensors under the desired operating conditions. This was further illustrated as the authors explored the long-term stability of NHC monolayers in buffered media, simulating the conditions of continuous biosensor operation. Their results were encouraging, showing that both NHC and MCH monolayers maintain their structural integrity over extended periods, even under serial voltammetric interrogation. This finding is particularly promising for the development of durable electrochemical sensors capable of operating in challenging environments, such as biofluids, where stability under continuous voltage cycling and resistance to biofouling are essential.

In conclusion, the new study demonstrated that NHC SAMs achieve promising organized assembly and stability on gold surfaces, offering valuable insights for the advancement of electrochemical sensor technologies. The authors’ findings highlight the potential of NHCs as robust alternatives to traditional thiol-based monolayers, opening new avenues for the development of stable, functionalized surfaces for a wide range of applications in biosensing and beyond.

About the author

Netzahualcóyotl Arroyo-Currás, also known as Netz Arroyo, is an Associate Professor in the Department of Pharmacology and Molecular Sciences at Johns Hopkins University School of Medicine. He obtained his graduate degree in Analytical Chemistry from the University of Texas at Austin in 2015, where he worked under the late Allen J. Bard. Upon graduating, he pursued postdoctoral training in bioengineering at the University of California Santa Barbara, under Kevin W. Plaxco. His laboratory at Hopkins pursues the development of electrochemical, aptamer-based biosensors for the study of molecular transport cross biological barriers in vivo.

About the author

David Jenkins joined the faculty of the University of Tennessee in 2008 and has been an endowed Ziegler Professor of Chemistry since 2020.  He received his Ph.D. in inorganic chemistry from the California Institute of Technology in 2005, under the direction of Jonas Peters.  Upon graduation, he joined the laboratory of Jeffrey Long as a Miller Institute for Basic Research postdoctoral fellow at the University of California, Berkeley.  His research focuses on the design of novel azole ligands for a wide variety of inorganic synthetic projects ranging from porous materials, to nanoparticles, to homogenous catalysis.

About the author

Jon Camden received his B.S. in chemistry and music from the University of Notre Dame in 2000 and his Ph.D. in physical chemistry from Stanford University in 2005.  After completing postdoctoral studies at Northwestern University, he joined the Department of Chemistry at the University of Tennessee as an Assistant Professor in 2008.  In 2014 he moved to the University of Notre Dame where he now serves as Professor and Director of Undergraduate Studies in the Department of Chemistry and Biochemistry.  His group’s research interests range from the optical properties of nanoparticles and ultrasensitive detection methods to electron beam characterization of plasmonic materials.

Reference

Pellitero MA, Jensen IM, Dominique NL, Ekowo LC, Camden JP, Jenkins DM, Arroyo-Currás N. Stability of N-Heterocyclic Carbene Monolayers under Continuous Voltammetric Interrogation. ACS Appl Mater Interfaces. 2023;15(29):35701-35709. doi: 10.1021/acsami.3c06148.

Go to ACS Appl Mater Interfaces.

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