ACS Appl Mater Interfaces. 2017 May 24;9(20):17653-17661. doi: 10.1021/acsami.7b04887.

Highly Efficient Fumed Silica Nanoparticles for Peptide Bond Formation: Converting Alanine to Alanine Anhydride.

Guo C1, Jordan JS1, Yarger JL1, Holland GP2.

1 School of Molecular Sciences, Magnetic Resonance Research Center, Arizona State University , Tempe, Arizona 85287-1604, United States.

2 Department of Chemistry and Biochemistry, San Diego State University , 5500 Campanile Drive, San Diego, California 92182-1030, United States.
 

Abstract

In this work, thermal condensation of alanine adsorbed on fumed silica nanoparticles is investigated using thermal analysis and multiple spectroscopic techniques, including infrared (IR), Raman, and nuclear magnetic resonance (NMR) spectroscopies. Thermal analysis shows that adsorbed alanine can undergo thermal condensation, forming peptide bonds within a short time period and at a lower temperature (∼170 °C) on fumed silica nanoparticle surfaces than that in bulk (∼210 °C). Spectroscopic results further show that alanine is converted to alanine anhydride with a yield of 98.8% during thermal condensation. After comparing peptide formation on solution-derived colloidal silica nanoparticles, it is found that fumed silica nanoparticles show much better efficiency and selectivity than solution-derived colloidal silica nanoparticles for synthesizing alanine anhydride. Furthermore, Raman spectroscopy provides evidence that the high efficiency for fumed silica nanoparticles is likely related to their unique surface features: the intrinsic high population of strained ring structures present at the surface. This work indicates the great potential of fumed silica nanoparticles in synthesizing peptides with high efficiency and selectivity.

KEYWORDS:

NMR spectroscopy; Raman spectroscopy; adsorption; alanine; alanine anhydride; fumed silica nanoparticles; thermal transformation

PMID: 28452465

 

Supplement: 

The adsorption and transformation of biomolecules on surfaces of inorganic materials play a crucial role in prebiotic chemistry, bio-nanotechnology, and drug delivery research. A fundamental understanding of the physical and chemical behavior of biomolecules at the interfaces of inorganic materials could help people to achieve the goal of developing novel biosensors and even finding the answer to the “Origin of Life”.

Amino acids serve as the basic building blocks of complex biomolecules such as peptide and proteins in nature. To fulfill the ultimate goal of overall goal of understanding complicated biological systems involving peptides and proteins, a very first step is to understand how amino acids interact and evolve at the interfaces.

In our previous work, we have carried out a thorough investigation of alanine adsorption on fumed silica nanoparticles using a combination of thermal analysis and solid-state NMR spectroscopy [1]. It is found that both the protonated amine group and the carboxyl group of alanine interact with the silanol group directly via hydrogen bonding when the sample is kept dry.

Here, in the recent work, we focus on investigating the peptide bond formation reaction during the thermal condensation of alanine on fumed silica nanoparticles. Combining multiple spectroscopic techniques, including infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy, it is discovered that alanine adsorbed on fumed silica nanoparticle surfaces is able to form a cyclic peptide, alanine anhydride, at ∼170 °C with a high selectivity and a high yield of approximately 100% (Figure 1). The significant finding indicates the great potential of fumed silica nanoparticles in synthesizing peptides on solid surfaces with high yield. A recent report has demonstrated that a programmable condition can be used to synthesize oligopeptides with a yield ∼50% [2]. Compared to that study, the method presented in this work shows an improved efficiency for peptide bond formation with a near 100% efficiency. To further unravel the mechanism of such high-selectivity and high-yield peptide formation on fumed silica nanoparticles, we carried out a comparative study of fumed and colloidal silica nanoparticles, and the results indicate that the high efficiency is very likely related to the intrinsic strained ring structures present at the interfaces of fumed silica nanoparticles that are not abundant in colloidal forms. This provides clear experimental evidence toward understanding the mechanism of “surface-catalyzed” peptide bond formation reactions on silica surfaces, since relatively less effort has been put forth on this topic compared to the extensive investigations on adsorption of amino acids on silica.

 

 

Figure 1. Thermal condensation of alanine on fumed silica nanoparticles surfaces. Alanine undergoes thermal condensation forming peptide bond around 170 °C with variable surface loading ratios on fumed silica nanoparticles surfaces (A). NMR spectroscopy provides quantitative results showing the peptide conversing efficiency is ~ 100 % (B).

 

References

  1. Guo, C.; Holland, G. P. Alanine Adsorption and Thermal Condensation at the Interface of Fumed Silica Nanoparticles: a Solid- State NMR Investigation. J. Phys. Chem. C 2015, 119 (45), 25663− 25672.
  2. Rodriguez-Garcia, M.; Surman, A. J.; Cooper, G. J. T.; Suarez- Marina, I.; Hosni, Z.; Lee, M. P.; Cronin, L. Formation of Oligopeptides in High Yield Under Simple Programmable Conditions. Nat. Commun. 2015, 6, 8385.