Elsevier

Carbohydrate Research

Volume 379, 20 September 2013, Pages 68-77
Carbohydrate Research

Synthesis, surface properties, and biocompatibility of 1,2,3-triazole-containing alkyl β-d-xylopyranoside surfactants

https://doi.org/10.1016/j.carres.2013.06.020Get rights and content

Highlights

  • Alkyl triazole xylopyranosides were synthesized from xylose using ‘click chemistry’.

  • Alkyl triazole xylopyranosides were moderately toxic to non-toxic in cells in culture.

  • Alkyl xylopyranosides with intermediate chain length caused apoptosis, not necrosis.

  • Long chain alkyl xylopyranosides form stable monolayers at the air–water interface.

Abstract

We are interested in the development of surfactants derived from hemicellulosic biomass, as they are potential components in pharmaceuticals, personal care products, and other detergents. Such surfactants should exhibit low toxicity in mammalian cells. In this study we synthesized a series of alkyl or fluoroalkyl β-xylopyranosides from azides and an alkyne using the copper-catalyzed azide-alkyne (CuAAC) ‘click’ reaction in 4 steps from xylose. The purified products were evaluated for both their surfactant properties, and for their biocompatibility. Unlike other carbohydrate-based surfactants, liquid–crystalline behavior was not observed by differential scanning calorimetry. The triazole-containing β-xylopyranosides with short (6 carbons) and long (>12 carbons) chains exhibited no toxicity at concentrations ranging from 1 to 1000 μM. Triazole-containing β-xylopyranosides with 8, 10, or 12 carbons caused toxicity via apoptosis, with CC50 values ranging from 26–890 μM. The two longest chain compounds did form stable monolayers at the air–water interface over a range of temperatures, although a brief transition to an the unstable monolayer was observed.

Introduction

The broad range of commercial applications of surfactants has increased the need for ones that are biologically safe.1 As the demand continues to grow, the importance of surfactants derived from renewable resources has risen. Carbohydrate-based surfactants often satisfy requirements of low toxicity and sustainable production, and have been used as pharmaceuticals, detergents, agrochemicals, and personal care products.1 The most readily available carbohydrates are glucose and xylose, which, together with lignin, are the components of lignocellulose. Recent advancements in the field have allowed for the use of materials derived from cellulose (glucose) and hemicellulose (glucose and xylose).2 The carbohydrate precursors are readily produced using environmentally friendly processes.3, 4 Additionally, carbohydrate-based surfactants often have low toxicities and can be biodegradable.

The synthesis and physiochemical characterization of xylose-based surfactants have been reported in the literature.5, 6, 7 These surfactants were typically synthesized by enzymatic or Fischer glycosylation reactions, or by hydrolysis of oligosaccharides. The products, which were unspecified mixtures of anomers, exhibited typical chemical properties of surfactants. Previously we have synthesized β-alkyl xylopyranosides as novel surfactants which exhibited liquid–crystalline behavior and low in vitro toxicity.8 To further expand the available structures of carbohydrate-based surfactants, we are interested in designing surfactants with linkers connecting the carbohydrate head group to the hydrophobic tail, allowing the rapid synthesis of diverse surfactants with different hydrophobic tails. Here we chose the 1,2,3-triazole, a heterocyclic moiety readily synthesized by a copper-catalyzed ‘click’ reaction between an azide and an alkyne, as a versatile linker. This heterocycle has found widespread usage9 in a broad range of disciplines such as medicinal chemistry and materials chemistry. The 1,2,3-triazole moiety has been found in bolaamphiphile,10 star-like,11 and fluorocarbon surfactants.12, 13 While both xylose head groups and 1,2,3-triazoles have been used in surfactants, the two have not been used in combination. Triazole-linked glucose-based surfactants have been synthesized previously either by the copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction of a glycosyl azide and a propargylated fatty alcohol or a propargylated sugar and an alkyl azide.14, 15, 16, 17 In this paper we report the synthesis and characterization of physiochemical properties of xylose-based carbohydrates containing a triazole linker as well as a preliminary biocompatibility assessment.

Section snippets

Synthesis of triazole-linked alkyl xylosides

We sought an efficient route to xylose surfactants containing hydrophobic chains of variable length linked to the polar head group with a 1,2,3-triazole generated by a ‘click’ reaction. This copper-catalyzed reaction of azides and alkynes proceeds under mild conditions with excellent regiochemistry; many functional and protection groups are tolerated.18 Furthermore, this ‘click’ reaction allows for short, straight-forward syntheses, as few functional group interconversions and protecting group

General methods

The 1H and 13C NMR spectra were recorded on multinuclear Bruker Avance 300 or Bruker DRX 400 Digital NMR spectrometers. Spectral assignments were determined from COSY experiments. 19F spectra were recorded using a Bruker Avance 300. The mass spectra were measured at the University of California, Riverside Mass Spectrometry facility. Elemental analyses were obtained from Atlantic Micro Lab Microanalysis Service (Atlanta, Georgia, USA). Melting points were determined using a MelTemp apparatus,

Acknowledgements

This work was supported by the National Science Foundation (CBET-0967381/0967390), the U.S. Department of Agriculture Biomass Research and Development Initiative (Grant Agreement 68-3A75-7-608) and the Department of Energy Development and Independence, Energy and Environment Cabinet of The Commonwealth of Kentucky. The cell culture work was performed at the Cell Culture Core of the Border Biomedical Research Center (BBRC) supported by grant 8G12MD007592 from the National Center for Research

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