Novel organotrichlorosilane surface chemistry towards covalent polyhistidine-tag immobilization and surface modification of piezoelectric lithium niobate for future biosensor development

Abstract

Aim: In biosensor technology, reliable attachment of protein-based probes requires careful control of the orientation of the probe molecule on the biosensor surface. In this regard, polyhistidine peptide became an attractive target for on surface immobilization. The present contribution details the total synthesis and the surface chemistry of a new antifouling organotrichlorosilane linker bearing a head function designed to immobilize the imidazole side chain of histidine for future immobilizations with polyhistidine peptide onto biosensor surface. Methods: A novel organotrichlorosilane linker bearing the ethylene glycol backbone and a 2-chloroethyl sulfone head function (which can be converted to the vinyl sulfone group for subsequent attachment with imidazole) were synthesized via a multiple-step synthesis and carefully characterized. Surface modifications using the synthesized novel organotrichlorosilane linker, subsequent conversion to vinyl sulfone head function, and treatment with N-protected histidine were demonstrated on black lithium niobate substrate. Results: Novel organotrichlorosilane linker was successfully synthesized, though it was also observed that organotrichlorosilane linker was quite moisture reactive. Surface characterizations also indicated successful modification of lithium niobate with the novel organotrichlorosilane linker as well as presence of N-protected histidine on the lithium niobate surface post-immobilization. Conclusions: A novel organotrichlorosilane linker bearing the 2-chloroethylsulfone group was successfully synthesized and successful immobilization with N-protected histidine was demonstrated. The surface chemistry demonstrated onto lithium niobate herein is immediately applicable for future on-surface immobilization of protein-based probe molecules bearing polyhistidine moieties.

Keywords

His-tag / lithium niobate / surface modification / antifouling / biosensor technology

References

[1] Fei C, Chiu CT, Chen X, Chen Z, Ma J, Zhu B, et al. Ultrahigh Frequency (100 MHz-300 MHz) Ultrasonic Transducers for Optical Resolution Medical Imagining. Sci Rep. 2016; 6: 28360.

[2] Mujahid A, Dickert FL. Surface Acoustic Wave (SAW) for Chemical Sensing Applications of Recognition Layers. Sensors (Basel). 2017; 17: 2716.

[3] Carville NC, Collins L, Manzo M, Gallo K, Lukasz BI, McKayed KK, et al. Biocompatibility of ferroelectric lithium niobate and the influence of polarization charge on osteoblast proliferation and function. J Biomed Mater Res A. 2015; 103: 2540-8.

[4] Candito M, Simoni E, Gentilin E, Martini A, Marioni G, Danti S, et al. Neuron Compatibility and Antioxidant Activity of Barium Titanate and Lithium Niobate Nanoparticles. Int J Mol Sci. 2022; 23: 1761.

[5] Feng CT, Cheng CK, Atashbar MZ. PMMA/64° YX-LiNbO₃ Guided SH-SAW based immunosensing System . In: Proceedings of IEEE Sensors; 2011 Oct 28-31; Limerick, Ireland. New York City: IEEE; 2011. pp. 308-311.

[6] Thompson M, Sheikh S, Blaszykowski C, Romaschin A. Biosensor technology and the clinical biochemistry laboratory - Issue of signal interference from the biological matrix. In: Vadgama P, Serban P, editors. Detection Challenges in Clinical Diagnostics. London (UK): Royal Society of Chemistry; 2013. pp. 1-34.

[7] Banerjee I, Pangule RC, Kane RS. Antifouling coatings: recent developments in the design of surfaces that prevent fouling by proteins, bacteria, and marine organisms. Adv Mater. 2011; 23: 690-718.

[8] Damodaran VB, Murthy NS. Bio-inspired strategies for designing antifouling biomaterials. Biomater Res. 2016; 20: 18.

[9] Blaszykowski C, Sheikh S, Thompson M. Surface chemistry to minimize fouling from blood-based fluids. Chem Soc Rev. 2012; 41: 5599-612.

[10] Sheikh S, Sheng JCC, Blaszykowski C, Thompson M. New oligoethylene glycol linkers for the surface modification of an ultra-high frequency acoustic wave biosensor. Chem Sci. 2010; 1: 271-75.

[11] Sheikh S, Blaszykowski C, Nolan R, Thompson D, Thompson M. On the hydration of subnanometric antifouling organosilane adlayers: a molecular dynamics simulation. J Colloid Interface Sci. 2015; 437: 197-204.

[12] Pawlowska NM, Fritzsche H, Blaszykowski C, Sheikh S, Vezvaie M, Thompson M. Probing the hydration of ultrathin antifouling organosilane adlayers using neutron reflectometry. Langmuir. 2014; 30: 1199-203.

[13] Latham AH, Williams ME. Versatile routes toward functional, water-soluble nanoparticles via trifluoroethylester-PEG-thiol ligands. Langmuir. 2006; 22: 4319-26.

[14] Zefirov NS, Zyk NV, Beloglazkina EK, Kutateladze AG. Thiosulfonates: Synthesis, Reactions and Practical Applications. Sulfur Rep. 1993; 14: 223-40.

[15] Hochuli E, Bannwarth W, Dobeli H, Gentz R, Stuber D. Genetic approach to facilitate purification of recombinant proteins with a novel metal chelate adsorbent. Nat Biotechnol. 1988; 6: 1321-25.

[16] Rusmini F, Zhong Z, Feijen J. Protein immobilization strategies for protein biochips. Biomacromolecules. 2007; 8: 1775-89.

[17] Liu YC, Rieben N, Iversen L, Sørensen BS, Park J, Nygård J, et al. Specific and reversible immobilization of histidine-tagged proteins on functionalized silicon nanowires. Nanotechnology. 2010; 21: 245105.

[18] Wasserberg D, Cabanas-Danés J, Prangsma J, O’Mahony S, Cazade P, Tromp E, et al. Controlling Protein Surface Orientation by Strategic Placement of Oligo-Histidine Tags. ACS Nano. 2017; 11: 9068-83.

[19] Wegner SV, Spatz JP. Cobalt(III) as a stable and inert mediator ion between NTA and His6-tagged proteins. Angew Chem Int Ed Engl. 2013; 52: 7593-6.

[20] Wegner SV, Schenk FC, Spatz JP. Cobalt(III)-Mediated Permanent and Stable Immobilization of Histidine-Tagged Proteins on NTA-Functionalized Surfaces. Chemistry. 2016; 22: 3156-62.

[21] Li M, Cheng F, Li H, Jin W, Chen C, He W, et al. Site-Specific and Covalent Immobilization of His-Tagged Proteins via Surface Vinyl Sulfone-Imidazole Coupling. Langmuir. 2019; 35: 16466-75.

[22] Ortega-Muñoz M, Morales-Sanfrutos J, Megia-Fernandez A, Lopez-Jaramillo FJ, Hernandez-Mateo F, Santoyo-Gonzalez F. Vinyl Sulfone functionalized silica: A “ready to use” pre-activated material for immobilization of biomolecules. J Mater Chem. 2010; 20: 7189-96.

[23] Speier JL, Webster JA, Barnes GH. The Addition of Silicon Hydrides to Olefinic Double Bonds. Part II. The Use of Group VIII Metal Catalysts. J Am Chem Soc. 1957; 79: 974-9.

[24] Blaszykowski C, Sheikh S, Benvenuto P, Thompson M. New functionalizable alkyltrichlorosilane surface modifiers for biosensor and biomedical applications. Langmuir. 2012; 28: 2318-22.

[25] Chan E. Novel Silane Surface Chemistry for Covalent Immobilization with N-protected Histidine: Towards Improved Functionalization of Hydroxylated Materials with His-tagged Biomolecules [dissertation]. Toronto (Canada): University of Toronto; 2024.

[26] Ford-Moore AH. 512. Divinyl sulphone and allied compound. J Chem Soc. 1949; 2433-40.

[27] Morpurgo M, Veronese FM, Kachensky D, Harris JM. Preparation of characterization of poly(ethylene glycol) vinyl sulfone. Bioconjug Chem. 1996; 7: 363-8.

[28] Standifer EM, Jundt DH, Norwood RRG, Bordui PF. Chemically reduced lithium niobate single crystals: processing, properties and improvements in SAW device fabrication and performance. In: Proceedings of the IEEE International Frequency Control Symposium; 1998 May 29; Pasadena, CA, USA. New York City: IEEE; 1998. pp. 470-2.

[29] Evans P, Taylor RJK. Conjugate Addition Reactions of Vinyl Sulfones with Hard Nucleophiles. J Sulfur Chem. 2005; 26: 481-97.

[30] Williams DL, Kuhn AT, Amann MA, Hausinger MB, Konarik MM, Nesselrode EI. Computerised Measurement of Contact Angles. Galvanotechnik. 2010; 101: 2502-12.

[31] Black RM, Brewster K, Harrison JM, Stansfield N. The Chemistry of 1,1’-Thiobis-(2-Chloroethane) (Sulphur Mustard) Part I. Some Simple Derivatives. Phosphorus Sulfur Silicon Relat Elem. 1992; 71: 31-47.

[32] Levitre G, Granados A, Molander GA. Sustainable Photoinduced Decarboxylative Chlorination Mediated by Halogen Atom Transfer. Green Chem. 2023; 25: 560-5.