When we think of silica, or silicon dioxide (SiO2), we consider its seemingly infinite forms and applications – both in its natural mineral form and as a synthetic product. We're familiar with products such as glass, silica gels, and desiccants. It is also widely used in pharmaceutical development, food and cosmetic production, as well as semiconductor manufacturing and other industries.

So, what is "functionalized silica", and how is it used?

Simply put, functionalized silica is silica that has been chemically modified to add new properties and capabilities to the surface of the silica gel.

Functionalization is a technique used in chemistry, nanotechnology, materials science, biomedicine and other disciplines – and it refers to attaching molecules or nanoparticles to the surface of a material through chemical bonding or adsorption to vary its properties for specific applications.

While any type of silica can be functionalized, the amount of achievable grafting will depend on the silica's specific surface area (and porosity to a lesser extent). Different applications demand different functionalized products. For an HPLC application, for example, a spherical silica would be chosen, and the particle size would be tailored to either analytical or preparative scales. For scavengers or supported reagents, we would typically use a 40 - 60 µm silica with a 60 Å pore size.

How is silica functionalized?

The silica surface possesses active silanol groups (Si-OH, free OH groups of the silica), which permits the modification of the surface chemistry by grafting various types of silanes to create monomeric or polymeric bonded phases. This process allows control of the silica surface polarity to enhance its utility in separation techniques.

Surface structure of functionalized silica gel

Surface structure of functionalized silica gel

SiliCycle uses an innovative grafting technique characterized by a homogeneous coverage of the functional groups on the surface. This proprietary process can be used with all silane types and ensures chemical stability and better performance due to the greater homogeneity of the surface. The molecules then typically go through an "endcapping" step for better stability.


When silica is functionalized, not all available silanol groups (free OH groups) on the silica surface react with the silane reagent, so the residual groups are "endcapped" with a capping reagent such as trimethylsilyl chloride to form Si-O-Si(CH3)3. This process eliminates undesirable interactions with the surface OH groups.

Endcapping renders the silica less acidic and less polar. Bare silica gel for chromatography with all its free silanols is polar and somewhat acidic (pKa ~5). In normal phase chromatography, this polar interaction is the basis for the separation. For functionalized silica used as a scavenger, a reagent or any other chromatographic phase, the only interaction that should occur is the one with the grafted function (not a non-specific binding with the surface).

Functionalization and endcapping processes

Functionalization and endcapping processes

While most silica products are endcapped, oxidants such as Si-KMnO4, Si-PCC, and Si-PDC are not because the silanols (free OH groups on the silica surface) are needed to preserve the efficiency of the material.

Both spherical and irregular silica can be functionalized, generally between 1 µm to 1,000 µm in particle-size and 30 Å to 1,000 Å in pore-size. Endcapped silica is insoluble in all standard organic solvents.

Silica vs. Polymer Matrices

Other than silica it should be pointed out that that polymer matrices also exist for separation and purification applications, however their use and efficiency vary based on the experimental conditions.

The two main advantages of using polymers are that it can be used in a wider pH range (from 0-14 compared to between 2-10 for silica) and that the loading capacity is slightly higher at 10% rather than of 5% for silica. However, there are some drawbacks as well.

Polymers are much more susceptible to leaching, which happens when the polymer condensation is not completed, and parts of it can dissolve in organic solvents. The polymer active sites are inside the matrix, so the rate of action is largely dependent on the rate of diffusion through the polymer. Polymers must be used in solvents that will allow it to swell (DCM, THF, CHCl3). This means that the product can get trapped inside the polymer, significantly affecting the yield.

The silica active sites are on the surface where they are more easily accessible, thus providing fast kinetics and high yields. Silica gel is not affected by any organic solvent because the pore structure is rigid and permanent and therefore is mechanically and thermally stable.

Therefore, silica gel offers faster scavenging, higher purity, improved yields, and ease of use with lack of static or extensive washing requirements. For these reasons, functionalized silica gel tends to be preferred.

How is functionalized silica used?

  • Chromatography stationary phases

    Silica gel is the most widely used packing material in chromatography columns. Selecting the best stationary phase for specific separation goals can be a challenge given the number and variety of phases on the market, with new ones introduced every year.

    For chromatographic applications, these sorbents are available for reversed-phase, normal phase, and ion exchange applications in bulk form or prepacked in preparative solid-phase extraction (SPE) or flash cartridges (check out our poster: SiliCycle Packing formats in a Nutshell). Custom functionalized gels can be designed using spherical or irregular silica particles at selected sizes and pore diameters.

  • Organic synthesis

    Functionalized silica gels are also used in organic synthesis and purification as insoluble reagents and scavengers. Purification procedures such as chromatography, liquid–liquid extraction, and crystallization can be time-consuming, difficult to scale up, require high volume of solvents and in many cases affect the recovery of the desired product. In many cases, supported reagents have distinct advantages over their solution-phase counterparts.

  • Supported reagent

    A supported reagent is a reactive functional group grafted onto insoluble silica. It is added at the beginning of the reaction and replaces the homogeneous reagent, allowing the reagent to be used in excess, driving the reaction to completion.

    Supported reagents also facilitate multiple-step, one-pot reactions, which reduces the separation process and purification time and yield. Spent reagents are easily removed by filtration. Bound reagents are an excellent alternative in cases where the reagent is used in excess and can be difficult to remove, such as triphenylphosphines. Purification becomes a simple filtration and evaporation process.

    Purification process using supported reagent

    Purification process using supported reagent

    Supported reagents such as Si-KMnO4 should be used in a solvent where the free reagent is not soluble. This way, the reagent stays on the silica for which it has more affinity. If a large amount of water is present, the reagent will be washed off or destroyed.

  • Scavengers

    Scavengers are functionalized silica gels designed to react and bind excess reagents, metal complexes, or by-products. Scavengers improve synthesis by acting as metal or organic chelators to purify mixtures contaminated by excess homogeneous reagent or metallic residue.

    Metal scavengers are designed specifically to react with and bind excess metal complexes. In the pharmaceutical industry, the push to bring candidate drugs to market quickly has increased the number of transition metal-catalyzed reactions that are transferred from lead optimization to early scale-up. Metal contaminants may be present in ingredients used in drug development during synthesis. Many trace metals are hazardous to human health, so efficient and effective removal of post-reaction metal residues is a major concern in the pharmaceutical industry as the thresholds set in new regulations are becoming increasingly challenging to reach.

    Metal scavenger reaction and binding process

    Metal scavenger reaction and binding process

    The traditional methods of purifying active pharmaceutical ingredients (APIs) from residual metal catalysts — chromatography, activated carbon, crystallization, distillation, etc.— can often involve high cost, time loss, high solvent consumption, low efficiency and reduced API yields which is not ideal.

    Metal scavengers have transformed the field. Due to their harsh mechanical stability, their resistance to minimal forms of leaching or swelling, durability up to 150 °C and extended shelf-life , they are considered benign. This makes them suitable for all R&D and manufacturing stages and can be introduced at any time in your process.

    Functionalized silica-based scavengers and their applications are detailed in our selection guide.

For more information

  • Functionalized silicas FAQ
    These "frequently asked questions address the differences between silica and polymer; use, handling, and storage of functionalized silica; and more.
  • SiliCycle's Complete Range of Functionalized Silicas
    Silicycle's functionalized silica gels include scavengers, chromatographic phases, reagents and oxidants, and linkers. The silica gels are typically made on standard SiliaFlash silica gel R10030B, with 40–63 μm, 60 Å. All functionalities are available on both spherical or irregular silica particles, as well as on any particle or pore size.
  • SiliaMetS® metal scavengers
    Learn about the process for using metal scavengers, as well as features and benefits.
  • Metal scavenger case studies
    SiliaMetS Metal Scavengers are being used by many pharmaceutical companies, from lab to production scale. Read success stories that highlight the ease of use and reliable performance of SiliaMetS.