Elsevier

TrAC Trends in Analytical Chemistry

Volume 118, September 2019, Pages 606-624
TrAC Trends in Analytical Chemistry

Use of thiol functionalities for the preparation of porous monolithic structures and modulation of their surface chemistry: A review

https://doi.org/10.1016/j.trac.2019.06.027Get rights and content

Highlights

  • Thiols can modulate the surface chemistry of the pores of monolithic structures.

  • Silica, organic and hybrid organo-silica monoliths can be functionalized by thiols.

  • Thiols immobilize metal nanoparticles on the pores of monolithic structures.

  • Metal nanoparticles work as linkers to thiols that control the separation mechanism.

  • Separations, extractions and catalysis benefit from thiols and porous monoliths.

Abstract

The state of the art concerning the use of thiol functionalities for the preparation of porous monolithic structures and modulation of their surface chemistry thus enabling a variety of applications is reviewed. The preparation of monoliths with thiol groups is achieved via a single-pot strategy or a parent monolith is prepared followed by post-synthesis modification. Both strategies lead to monolithic structures which applications benefit from the reactivity of thiols. Current thiol functionalized monoliths are formed from silica, synthetic polymers, and hybrid organic-silica materials. Preparation of monolithic columns for chromatography is described as well as the production of heterogeneous catalytic reactors in which the affinity of metal nanoparticles to thiols is used. The application of thiol-ene click reactions for the construction of polymer monoliths is then illustrated. Finally, we discuss the hybrid organic-silica monoliths emphasizing their preparation from polyhedral oligomeric silsesquioxanes. These monoliths are well suited for functionalizations and assist the various click reactions.

Introduction

Monolithic stationary phases emerged in the late 1980s and early 1990s. They can be described as a single piece of porous materials prepared from organic polymer [1], inorganic sol-gels [2], [3], and hybrid organic-inorganic precursors [4], [5], [6]. A recent review outlined the synthetic routes, functionalization and analytical application of monolithic columns [7]. The historical development of monolithic columns was recently reviewed [8]. Monoliths feature up to micrometer large interconnected through pores that enable the passage of the liquid phase at high flow rates under low to moderate back pressures. Mass transport in these monoliths is controlled by fast convection rather than by slow diffusion, thus speeding the processes.

One of the motivations for the development of the current monolithic columns was the possibility of the separation of proteins in very short columns only a few mm long proposed by Moore and Walters in 1984 and reiterated by Mal'tsev et al., in 1990 [9], [10]. However, packing of such short devices with small particles was very difficult resulting in severe channeling and poor chromatographic performance. In contrast, the organic polymer-based monoliths were prepared by polymerization of a homogeneous solution of monomers and porogenic solvents in situ within confines of a mold. This approach circumvented the difficulties characteristic of packed devices and enabled obtaining reproducible and efficient stationary phase in a short column, as demonstrated by Tennikova et al. [11]. Several other groups followed this seminal work confirming the feasibility of the preparation of polymeric monolithic columns in different shapes and sizes for chromatographic separations and sample preparation [1], [12]. More recently, the advent of miniaturization in liquid chromatography benefited from the monolithic materials since it is much easier to fill capillaries and microfluidic systems with a homogeneous polymerization mixture or sol–gel precursors and to create the solid phase in situ than packing them with particles [13].

Monoliths can be divided in three groups: (i) organic, (ii) inorganic, and (iii) hybrid organic-inorganic materials. Organic polymer monoliths are readily prepared in a mold by thermal or photo-initiated polymerization of a mixture of monomers, porogenic solvents, and a free radical initiator. Examples of typical functional monomers and crosslinkers are given in Fig. 1. The in-situ preparation enables the fast production of columns since once the polymer matrix is synthesized, the column is washed to remove the non-polymerized components, mostly porogenic solvents, and is ready to use. However, adopting this approach, a tedious optimization of porogenic solvents and reaction conditions is needed each time after changing monomer/precursor to obtain a monolith with desired properties. Also, while using monomer with specific functionalities, a significant part of these functional groups can be buried within the polymer backbone and unavailable for the application [14]. Another option that requires at least two steps includes use of a well-optimized preparation protocol in the first step to obtain a generic reactive monolith with desired pore structure. The chemistry of this monolith is then formed in the second step via polymer analogous reaction without affecting the morphology. For example, copolymers of glycidyl methacrylate 1 or styrene 2 can be easily modified to produce monolithic columns for cation and anion exchange chromatography, as well as for metal and protein affinity chromatography [12], [15].

Inorganic monoliths are prepared by sol-gel transitions of alkoxysilanes (Fig. 2) including hydrolysis and polycondensation reactions. Typically, these columns are prepared from a mixture of tetrametoxysilane (TMOS) 24 or tetraetoxysilane (TEOS) 25 as the silica precursors in the presence of poly (ethylene glycol), urea, and acetic acid. The silanol groups are then functionalized with C8 and C18 ligands, and can also be converted to ion exchangers [2], [3]. Since a significant shrinkage accompanies the preparation, the analytical monolithic silica columns cannot be prepared in situ. The monolith is first prepared and then encased in the column tube.

While both silica- and organic polymer-based monoliths contain the micrometer large flow-through pores, the silica-based monoliths also include mesopores that provide for the enhanced surface area. The presence of mesopores and the high surface areas facilitate fast and efficient separation of small molecules using these columns. In contrast, organic polymer monoliths featuring only the large flow through pores have a surface area of a few tens of m2 g−1 due to the absence of mesopores. Therefore, these monoliths are not suitable for the separation of small molecules. However, they are very efficient in the separations of large molecules such as proteins, DNA, and soluble synthetic polymers, as well as large objects including viruses and virus-like particles [16], [17], [18], [19], [20]. Several researchers focused on the improvements of the separation of low molar mass substances using polymer monoliths as demonstrated in several reviews [21], [22], [23], [24], [25], [26]. Another difference between organic polymer and silica-based monoliths lays in their chemical stability. The silica-based monoliths can be safely used at pH values ranging between 3 and 7.5 while polymer monoliths are stable in the entire pH range and can be easily used under harsher conditions such as those typical of ion exchange chromatography.

Currently, significant efforts are also dedicated to the development of hybrid organic-silica monolithic columns since they share the benefits such as large surface area (tens to hundreds of m2 g−1), the presence of mesopores, and the mechanical stability of the silica monoliths with the wide pH range tolerance of the polymer-based monolithic columns [27]. This family of columns can be used for the separations of both small and large molecules [6], [28], [29], [30]. They are typically prepared via a single pot approach from functional monomers and silica precursors [27], [29]. These monoliths can be then modified to create a variety of functionalities enabling control of the chromatographic separation mechanisms. Fig. 2 shows structures of several silica precursors used for the preparation of both silica and hybrid organic-silica monolithic columns.

Section snippets

Thiols in silica monoliths

Several thiols shown in Fig. 3 have already been used for the preparation of monolithic chromatographic columns. However, only a few examples illustrate benefits of the thiol reactivity in silica-based monoliths. As known, the silanol groups at the pore surface can react with alkoxysilanes in condensation-like manner involving the electron pair of the oxygen in silanol and the Si atom of the alkoxysilane while releasing molecule of an alcohol. If the reaction is carried out in a dry

Thiols attached to polymer monoliths via ring opening reactions

The epoxy groups of poly (glycidyl methacrylate-co-ethylene dimethacrylate) [poly (GMA-co-EDMA)] monolith were easily converted to thiols by ring opening reactions for example with sodium hydrogen sulfide [33] and cysteamine 35 [34]. The thiol groups of this modified poly (GMA-co-EDMA) monoliths can further accommodate a multiplicity of surface chemistries enabling specific chemical interactions [12], [33].

For example, the 2,3-epoxypropyl groups of this monolith were transformed to

Immobilizing metal nanoparticles

Nanoparticles, which size is less than 100 nm, feature a high surface-to-volume ratio [39]. Their large surface area also provides a platform for the attachment of a large number of functionalities [34]. Nanoparticles can be immobilized on surface of the flow-through pores in a two-step manner with negligible reduction in the permeability [40]. Metal nanoparticles are strongly attracted to thiols through multiple metal-thiol bonds. They then can create an almost continuous layer at the pore

Click reactions in polymer monoliths

Click reactions are driven thermodynamically and occur quickly, irreversibly, and with a high specificity and yield to produce a single reaction product [55]. Generally, reactions that fit the definition of “click reactions” must meet the following criteria: (i) high efficiency and selectivity, (ii) quantitative (or near quantitative) yields, and (iii) be simple to perform under mild conditions, preferably in the presence of water and/or oxygen [56]. The ease of implementation of click

Functions of thiols in hybrid organic-silica monoliths

Owing to their chemical stability, presence of mesopores and wide variety of commercially available precursors, significant efforts has been recently dedicated to the hybrid organic-silica based materials [72]. Progress in this field was summarized in excellent review articles published by Ou et al., in 2015 [29] and by Zajickova in 2017 [27]. Three major approaches lead to the hybrid organic-silica monoliths: (i) sol-gel process originating from a mixture of trialkoxysilane and

Conclusions and outlook

Monolithic columns are a relatively new versatile alternative to the conventional chromatographic columns packed with particle. Organic polymer-based and hybrid organic-silica monolithic columns shine in the ease of preparation in a variety of shapes including analytical size columns, capillaries, and thin layers. This diversity succeeds since the homogeneous solution, sol/gel, or silica precursors are filled in a mold instead of packing with particles. The large flow-through pores aid high

Acknowledgments

Research on monolithic materials has been funded by grants 2013/18507–4 from the São Paulo Research Foundation (FAPESP) and 303940/2017–4 from the National Council for Scientific and Technological Development (CNPq). LFR acknowledges CNPq for a Ph.D. fellowship (Grant 161769/2014–4). Support of FS by the project EFSA-CDN (No. CZ.02.1.01/0.0/0.0/16_019/0000841) co-funded by the ERDF is also gratefully acknowledged.

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