INTRODUCTION
Imparting desired properties to silica surfaces to obtain functionalized silica surfaces is usually effected in different directions. In some cases, it is necessary to moderate interactions between surrounding molecules and surface sites, while in other cases, such interactions should be enhanced to prepare modified matrices with high specificity and selectivity. Besides, functionalization of silica surfaces is often carried out to immobilize diverse compounds to make them heterogeneous. A description is provided for chemical reactions, which are used to modify surfaces and to produce functionalized silica surfaces. A consideration is given to basic principles that should be adhered to when applying functionalized silica surfaces to various types of chromatographic separation [in such cases as stationary phases in gas and liquid chromatog-raphy, reversed and normal phases in high-performance liquid chromatography (HPLC) and affinity chromatography, chiral stationary phases for separating optical isomers]. Examples are presented which are intended to illustrate the production of highly specific and complexing adsorbents based on silicas with functionalized surfaces and their application in solid-phase extraction (SPE) of ions and molecules. A general outline is made of methods for activating surfaces of silica matrices with a view to heterogenize metal complex catalysts, to immobilize enzymes and other biologically active compounds. Also included is a brief analysis of the practical experience acquired in the sphere of application of functionalized silicas in the capacity of chemically active fillers of polymeric compositions and effective thickeners of dispersion media. Some consideration is also given to the state of the art and scope for research into the application of functionalized silica surfaces in formation of nanostruc-tures in various fields of modern materials science (sensitive elements of sensing devices, organically modified silicates, organically modified ceramics, etc.).
GENERAL NOTIONS
The wide practical use of synthetic silicas (precipitated and pyrogenic silicas, silica gels, and aerogels of silica) in medern material science and other fields in the capacity of fillers of polymers, thickeners of dispersion media, adsorbents, supports of catalysts, and active compounds is attributable to their chemical, mechanical, and microbio-logic stability (silica preparations are resistant to high temperatures, ionizing radiation, oxidizing and reducing agents, solutions of all acids with the exception of the hydrofluoric one; they do not swell in organic solvents and are distinguished for their high mass exchange rate) and to the possible regulation (within certain limits) of their main geometrical characteristics: value of specific surface area, size of particles, diameter, and distribution of pores.[1]
The chemical modification of silicas further broadens the opportunities for their effective use because, after deposition or chemical attachment of various functional compounds to the silica surface, the formed functionalized silica surfaces (FSS) retain the major characteristics of starting silica matrices while the attached compounds impart new properties to the support.[2-4] Although the modification of silica surface is effected through a thermal treatment (dehydration and dehydroxylation), hydrother-mal treatment (hydroxylation and hydration), adsorption of diverse substances (particularly substances with a large molecular weight), and deposition of carbon or metals, the most ample opportunities for a purposeful change of silica properties are provided by the attachment of one chemical compound or another as a result of various chemical reactions with the participation of surface sites. At present, mechanisms of such reactions as well as structures of the formed surface compounds are studied via spectroscopy in infrared (IR), ultraviolet (UV), and visible regions, solid-state 29Si, 13C (and other nuclei) cross-polarization magic-angle spinning nuclear magnetic resonance method (CP-MAS NMR), isotope exchange combined with mass spectrometry, and other contemporary physicochemical techniques.[3-5] Under favorable conditions (particularly in nonporous, highly disperse preparations of fumed silicas), infrared spectroscopy enables one to exert a practically direct control over the proceeding of chemical reactions in a surface layer.
The approach employed for imparting desired functional properties to the silica surface depends on the nature of the practical or scientific task in question, and may involve such major methods as weakening of intermolec-ular interactions of surrounding molecules with sites of the surface, enhancement of these interactions with a view to lend specificity and selectivity to the surface, and modification of the silica surface to transfer surface compounds to their heterogeneous state (immobilization of active compounds). Specifically, the substitution of structural silanol groups by methylsilyl groups through reactions with appropriate organosilicon compounds substantially moderates the energy of adsorption of polar adsorbates (one can observe a decrease in values of adsorption and heat of adsorption), and the silica surface acquires stable hydrophobic properties. At the same time, such a chemical modification of surface prevents the aggregation of disperse silica particles and facilitates their more uniform distribution in hydrocarbons and polymeric media. Moreover, attachment of sufficiently long hydrocarbon radicals (C16-C18) makes it possible to use such modified silicas as a basis for creation of adsorbents intended to concentrate organic compounds, which is of importance in designing methods of analysis for contents of pesticides and other organic impurities when effecting monitoring of environment.[6]
Attachment of a layer of chemically grafted organic radicals with various functional groups (—NH2, —COOH, — CH=CH2, —CN, —SH, etc.) that differ in their physicochemical properties and reactivities enables one to enhance desired characteristics of the silica surface, which offers ample scope and novel potentiality for practical application of FSS. Similar functional silicas find much use in the normal-phase variant of high-performance liquid chromatography. Besides, they may hold considerable promise in the development of chemically active fillers of polymers and in the design of selective adsorbents including highly specific affinity and immune affinity adsorbents for separation and purification of biopolymers.
Furthermore, FSS acquired great importance in the sphere of production of heterogeneous metal complex catalysts and immobilization of enzymes, other biologically active compounds, antibodies, cells, sections of tissues, and microorganisms on an inorganic matrix. This approach holds promise for the development of chemical and biological sensors whose application makes it possible to exert a pulsed or continuous control over corresponding components in a gas phase or liquid medium. For example, chemical modification of the surface of electrodes with functional organosilicon compounds (sol-gel transformations) is rather widely used for the attachment of electroactive compounds in a surface layer (electrochemical sensors). From this standpoint, the most promising technique is the chemical binding of an active compound, because the construction of sensing elements of control systems via polymer encapsulation methods does not provide a perpetual accessibility of an active compound and uniformity of its distribution in a film as well as a necessary strength of bonding with the electrode surface.
TYPES OF CHEMICAL REACTIONS USED TO PRODUCE FUNCTIONALIZED SILICA SURFACES
Most of the reactions used to produce FSS are classified among heterolytic processes of electrophilic or nucleo-philic substitution (SE or SN), addition (AdE or AdN), and elimination (E).[3,7] The surface groups are considered as centers of attack whose direction is determined by the character of electron density distribution on the atoms of surface sites participating in a chemical reaction, and by the nature of a corresponding electrophilic or nucleophilic reagent. From this point of view, one can expect that silicon atoms on the silica surface (to be more exact, atoms that are members of groups =SiOH or =SiOSi=) are more preferable for an attack by nucleophilic reagents. In contrast, oxygen atoms as members of the same groups are more preferable for an attack by electrophilic reagents. Possible types of heterolytic reactions involving silica surface sites are represented below:
Among the reactions used for chemical modification of a surface, there is a large class of processes where an attack is carried out by an electrophilic reagent through oxygen atoms of silanol groups of the surface. These processes are referred to as reactions of electrophilic substitution of protons (SEi). They proceed during interactions with various chloro- and alkoxysilanes, organosilazanes, organosiloxanes, numerous organoele-mental compounds, and halogenides of various elements. The class also includes processes of electrophilic addition (AdE) to groups =SiOH (for example, in the case of isocyanates or ethylene imine). In particular, the interaction between various trimethylsilylating reagents and silanol groups of the silica surface involves an attack on
oxygen atoms and proceeds according to the scheme (shown above).
Another class of reactions involves an attack of a nucleophilic reagent on silicon atoms of the silica surface. This class includes processes of nucleophilic substitution (SNi) (e.g., interactions between silanol groups of the surface and hydrohalogens or alcohols) and processes of nucleophilic addition (AdN), e.g., reactions of a solid-phase hydrosilylation of olefins,[8'9] with participation of groups =SiH attached to the silica surface:
In a number of cases, the function of reactive sites on the silica surface is simultaneously performed by silicon atoms and oxygen atoms of siloxane bonds so that the corresponding processes proceed by mechanism AdNE, for example:
It is also necessary to allow for the possible proceeding of elimination (E) and rearrangement processes with participation of chemical surface compounds.
Introduction of new sites (e.g., groups =SiR, =SiOR, =SiNH2, =SiHal, =SiH, etc. where R is an aliphatic or aromatic radical and Hal is a halogen atom) into a surface layer of silica leads to an increase in the number of potential heterolytic transformations with their participation. Grafted organic radicals can also participate in homolytic processes of substitution or addition (SH or AdH). These processes have been the subject of experimental studies, but the amount of experience gained for the present is not large.
FUNCTIONALIZED SILICA SURFACES IN CHROMATOGRAPHY AND SOLID-PHASE EXTRACTION
Functionalized silica surfaces provide considerable expansion of capabilities of chromatography and sorption techniques, which find much use for separation, purification, and concentration of substances.[2,10-13] It is appropriate to mention here that in various types of chromato-graphic separation [gas-adsorption chromatography, high performance liquid chromatography (HPLC), affinity chromatography], a surface layer of silica should contain sites that are able to participate in diverse kinds of in-termolecular interactions. Thus, gas-adsorption chroma-tography and reversed-phase HPLC make use of siliceous supports with attached nonspecific methyl, phenyl, octyl, octadecyl groups, while in the case of normal-phase HPLC, it is necessary to use FSS with quaternary ammonium compounds or with aminopropyl, cyanopropyl, carboxyl, propylsulfo, alkyldiol, and other groups capable of participating in donor-acceptor interactions with molecules of compounds which are separated. In affinity chromatography, which depends on the formation of bio-specific complexes (enzyme-substrate, enzyme-inhibitor, lectin-glycoproteid, antigen-antibody, etc.), one of the constituents of such a complex should be chemically bonded to the surface of a silica matrix. The function of a biospecific ligand is most often performed by lectins, protein A, certain dyes, polysaccharides, amino acids, monoclonal, and polyclonal antibodies, which are attached to functional silica surface with the help of diverse cross-linking agents. Determination of contents of medicinal preparations in biological fluids containing substantial amounts of albuminous compounds calls for the application of porous FSS of diphilic nature, i.e., there should be a hydrophilic external surface (accessible for proteins) and organophilic internal surface (inaccessible to proteins). Such a structure of FSS makes it possible to retain macromolecules of proteins on the external surface of a sorbent and to effect the separation of medicinal preparation molecules (which have smaller sizes and which interact with the hydrophobic internal surface of pores) via reversed-phase mechanism. It should also be noted that functionalized silica surfaces find use for covalent (chemospecific) chromatography of biopolymers. This chromatography technique is based on reversible chemical reactions between functional groups of modified silica and of a compound, which is separated. It is appropriate to mention here thiol-containing silicas activated with Ellman’s reagent,[14] which are suitable for the isolation and purification of thiol-containing enzymes, proteins, or peptides with the aid of the following reversible reaction proceeding by the thiol-disulfide exchange mechanism (see above).
Functionalized silica surfaces form the basis for designing effective chiral stationary phases for separation of optical isomers. With the view of producing enantio-selective sorbents of this kind, the chiral selectors of various electronic and geometric structures are attached to the silica surface. Such grafted selectors must afford to provide two- or three-point interactions with separated optical isomers.
Also significant is the fact that FSS are employed for adsorption concentration of ions and molecules in analytical practice [solid-phase extraction (SPE)].[6,n_13] For instance, columns containing FSS with grafted octadecyl-silyl groups are used for preconcentration of phenols, pesticides, and herbicides. Octadecylsilica with adsorbed derivatives of dithiocarbamates, crown esters, and other compounds is utilized for SPE of metals. In particular, C18 columns with adsorbed tri-n-octylphosphine oxide are used for extraction and determination of uranium and thorium in water.[16] In the case of a repeated use of C18 cartridges with adsorbed bonding or complexing compounds, there proceeds a gradual elution of such compounds from the surface of a sorbent. Therefore, many researchers put forth their efforts to develop methods for chemical bonding of most important analytical reagents on silica and other appropriate matrices. Such modified silicas with covalently bonded complexing compounds are referred to as complexing silicas. By now, efforts have yielded a number of rather versatile methods suitable for immobilization of a large majority of analytical re-agents.[11] Characteristically, the researchers of such methods derived benefit from the experience, which was acquired when designing procedures for immobilization of enzymes and other biologically active compounds on inorganic matrices. For example, to attach 4-(2-pyridyl-azo)resorcinol, 1-(2-pyridylazo)-2-naphthol, and 8-hydro-xyquinoline to the silica surface,[17] a use was made of the single-stage Mannich reaction (see below).
Although complex-forming adsorbents based on organic polymers possess an increased capacity with respect to extracted compounds in comparison with mineral supports, the developed FSS with grafted analytical reagents do not swell in water and organic solvents. Moreover, they are distinguished for their high rate of mass exchange with a surrounding medium and, hence, for better kinetic characteristics.
Complexing silicas may be classified according to the nature of an attached functional group (nitrogen-, oxygen-, sulfur-, phosphorus-containing silicas; modified silicas with functional groups involving unsaturated carbon-carbon bonds; polyfunctional silica surfaces)[3] or according to the nature of a bond between an ion and a grafted ligand (donor-acceptor bonds, ion exchange, charge-transfer complexes, inclusion complexes of the ”host-guest” type).
METAL COMPLEX CATALYSTS ANCHORED ON SILICAS
It is known that complexes of transition metals are attached to support surfaces (including FSS) for the purpose of producing catalysts that preserve the specificity and selectivity of homogeneous metal complexes and gain technological advantages afforded by heterogeneous contacts.1-18’191 Attachment of metal complexes to a surface prevents the agglomeration of coordination unsaturated sites and enhances the thermostability of complexes. At the same time’ one cannot foretell the possible influence of the surface of a support on the catalytic activity and selectivity of attached complexes. Although production of heterogeneous metal complex catalysts on siliceous matrices involves adsorption (metal complexes preliminarily prepared by using suitable solvents as well as metal complexes concurrently synthesized in a surface layer with participation of metal ions and of adsorbed ligands) or ion exchange, the most commonly employed methods consist of formation of coordination bonds between metal ions and ligands chemically bonded to surface. In this case, FSS performs the role of a polymeric macroligand. Anchoring of organic ligands on surfaces of silicas is also often accomplished by using functional organoalkoxysilanes whose functional groups, which contain ligands, are bound to surface through hydrolyt-ically stable bonds Si—C, while alkoxy groups and silanol groups form bonds Si—O—Si. For example, anchoring of phosphorus-containing ligands on the silica surface and subsequent formation of metal complexes with rhodium (Wilkinson catalyst), which are active in reactions of hydrogenation of various olefins, can be effected according to the following general scheme.
Introduction of oxygen- and nitrogen-containing lig-ands and ions of various transition metals makes it possible to obtain heterogeneous metal complex catalysts possessing high activity and selectivity in processes of linear and cyclic oligomerization, hydroformylation, hydrosilylation of olefins, and in some other reactions. Attachment of chiral ligands and complexes on FSS enables the possibility of substantially expanding the potentialities of asymmetric heterogeneous catalysis, which is employed for synthesis of optically active compounds. Also of further interest is the application of metal complexes anchored on FSS in reactions of transfer and activation of oxygen.
IMMOBILIZED ENZYMES AND FUNCTIONALIZED SILICA SURFACES
The main aim of immobilization is the production of heterogenized enzymes, which are readily separated from reaction media and which can be repeatedly used under flow reactor conditions. Immobilization of enzymes on silica matrices is effected by both the adsorption method and method of covalent binding on surface.1-20,21-1 Chemical bonding permits one to create more stable immobilized preparations, particularly preparations that are elution-resistant in varying surrounding medium factors (ionic strength, pH, concentration of a substrate, and content of substances which may lead to desorption of enzymes).
At present, the available range of methods for covalent bonding of enzymes with silica surface is rather broad. As a rule, all of them involve a preliminary modification of surface by bifunctional silane and subsequent introduction of active groupings that are able to form covalent bonds with side residues of amino acids of enzymes. The most commonly employed method is a preliminary modification of silica by 3-aminopropyltriethoxysilane and subsequent activation of the surface by various reagents (such as glutaraldehyde, diazonium salts, isothiocyanates, car-bodiimides, acylazides, haloalkyls, acid chlorides).1-22-1 Good performance is also shown by methods for activating the aminoorganosilica surface with 2,4-toluene diiso-cyanate (a) and cyanuric chloride (b) (see below).1-141
The function of starting organosilicas used for production of activated matrices can be performed not only by aminoderivatives but also by organosilicas with other functional groups (such as =SiCH=CH2, =SiH, =SiRSH). In particular, activated silica matrices for immobilization of enzymes were prepared through reactions between grafted vinyl groups and maleic anhydride, addition of acrolein to surface silicon hydride groups, and interaction of grafted sulfhydryl groups with Ellman’s reagent.[14]
Because the properties of an immobilized enzyme are determined by a package of properties of a biocatalyst and support and are dependent on the method for binding the biocatalyst to the support surface, when carrying out a concrete task it proves useful to test various methods for binding with a view to choose the procedure which is optimal from the standpoint of activity and stability of products. In porous silica matrices, the geometric characteristics of a support exert a substantial effect on the rate of binding of enzymes, on the capacity of a matrix with respect to a protein, and on the manifestation of activity of immobilized preparations, which is attributable to inside-diffusion retardation. The activity of immobilized preparations is, to a great extent, dependent on the pH of a medium where binding of an enzyme takes place. It has been observed that the maximum degree of binding of a protein to the silica surface is observed at pH values close to the isoelectric point of the protein.
Although the practical application of immobilized enzymes has considerable potential in fine organic synthesis and in various fields of biotechnology, it is in the creation of biosensors that their application is most impressive. In biosensors, a use is made either of flow minireactors with immobilized enzymes or of a biocata-lyst that is attached directly to the surface of ion-selective electrodes. In the first case, the function of supports is performed by silica-based materials, which possess a rigid structure and, therefore, set good hydrodynamic conditions in a flow of a buffer and of a solution that is analyzed. Placing an appropriate transducer at the outlet of such a minireactor with an immobilized enzyme makes it possible to create analyzers for a broad spectrum of substances, which are substrates or effectors of the enzyme. The role of transducers is most often played by an oxygen electrode, flow spectrophotometer, H+- and other ion-selective electrodes, as well as by a multipurpose enthalpimetric transducer. In the second case, enzymes are directly immobilized on the surface of a sensitive element (such as ion-selective field-effect transistor, piezoelectric quartz element, optical fiber element). So long as the supports used contain silicon dioxide, the chemical attachment of enzymes to their surface should be effected with allowance for the experience acquired in the sphere of immobilization of active compounds on modified silicas.
In recent years, there has been considerable interest in effecting enzyme-catalyzed reactions in nonaqueous solvents with a view to increase yields of products or to carry out novel syntheses. Because of their stability in organic solvent, silica matrices may hold considerable promise in the capacity of supports for appropriate enzymes. For example, it is possible to perform synthesis of various peptides with the help of immobilized proteases and with allowance for reversibility of hydrolysis of peptide bonds.[14] In this case, as a consequence of the absence of racemization, the prepared products possess a higher optical purity in comparison with products prepared via the classical peptide synthesis.
FUNCTIONALIZED SILICA SURFACES IN POLYMERS AND DISPERSION MEDIA
In numerous cases, efficiency of the application of functionalized silica surfaces in polymers and dispersion media is determined by the ratio of hydrophilic sites to hydro-phobic sites in a surface layer. This index is of critical importance for thickeners of lubricants and fillers of polymeric materials. Substitution of surface hydroxyl groups by grafted organic radicals favors a better distribution of silica particles in organic media. At the same time, the complete screening of the silica surface (e.g., by alkyl groups) may impair structural and mechanical characteristics of thickened systems, and filling of polymeric materials may worsen their physicomechanical properties.
A substantial reinforcement of filled systems can be attained in the situation when active sites of FSS (-NH2, -COOH, -SH, =SiH, etc.) are capable of chemical interaction with functional groups of polymeric macro-molecules. Such a chemical mechanism of reinforcement was employed for the first time in glass-fiber composites.1-23-1 From this standpoint, functionalized silica surfaces containing grafted amine groups may hold considerable promise as chemically active fillers of chlorine- and bromine-containing elastomers and copolymers, epoxy resins, polyurethane rubbers, melamino-formaldehyde and resorcinol-formaldehyde latex and resins, sulfonated eth-ylene-propylene-diene terpolymers, carboxyl-containing polymer systems. Specifically, in the case of introduction of FSS with amine groups into carboxyl-containing polymers, formation of salt-type cross bonds between the filler and polymer is observed:
On the contrary, FSS with carboxyl groups may considerably reinforce butadiene-vinylpyridine copoly-mer, elastomeric terpolymer of vinylpyridine, styrene, and butadiene, etc. FSS with grafted unsaturated groups can be advantageously employed for reinforcement of a broad range of olefin-containing copolymers and elastomers. Chemisorption of sterically hindered phenols on the surface of highly disperse silicas makes it possible to produce fillers and thickeners having antioxidant properties.
Applications of highly disperse silica in varnishes and paints are based on the thixotropic properties of this thickener and on its ability to increase the viscosity of systems and to decrease the sedimentation of pigments of various types. One of the salient features of such systems with siliceous thickeners lies in the fact that, at an infinitely small shearing stress, their behavior is similar to that of solids, and at high shearing stresses, to that of liquid compositions. The thixotropic properties of highly disperse silica are related to the deformation caused by shear, stirring, or shaking, which leads to breaking of bonds at points of contact of particles (of aggregates of particles) or of solvate shells of particles, and to their subsequent restoration at the state of rest. Application of functionalized silica surfaces enables one to exert control over the viscosity of a system and to substantially enhance the water-resisting property of a coating.
CONCLUSION
Purposeful variation of properties of the surface of silicas is of great importance in carrying out numerous scientific and practical tasks in adsorption, chromatography, catalysis, and chemistry of filled polymers. Presently, function-alized silica surfaces find much use in the production of immobilized reagents, which are successfully employed in synthetic organic chemistry.[24] Of particular significance is the ever-growing role of FSS in modern material science and nanodimensional engineering. Also noteworthy is the prevalent use of polysilsesquioxanes produced by the sol-gel method (cohydrolysis of organofunctional trialkoxysilanes and tetraalkoxysilane), organically modified silicates (ormosils) including silicates doped with diverse dyes, and organically modified ceramics (ormo-cers) for producing novel optical materials and lasers, sensitive elements of sensing devices, biocompatible ceramics.[25-29] New vistas in the production of FSS are furnished by chemical modification of surface and core of ordered mesoporous siliceous materials (such as MCM-41 and MCM-48),[30] which possess an exceptionally extended surface and unique structure of pores accessible to large molecules. It is not ruled out that such FSS will form the basis for the development of new generation adsorbents and catalysts. Also of significance is the formulation and establishment of principles of mosaic nanodimensional modification of siliceous supports because, under favorable conditions on the surface of such supports, it is possible to construct models of active centers of multicomponent metal complex catalysts and biological catalysts, as well as to create ultraselective and affinity sorbents. Functionalized silica surfaces are increasingly used in the field of novel dispersion media, polymeric compositions, and modern materials.
