Adsorptive separation of propylene (C3H6) and propane (C3H8) is an alternative to energy-intensive distillation, but improving kinetic selectivity is challenging for molecules with similar sizes. Composite materials consisting of a barrier organic film on the external surface of a zeolite have shown higher selectivity; however, structure-function relationships for these materials are lacking. Here, gas adsorption rates on zeolite 5A were controlled by varying the terminal functional group (amine or carboxylic acid) and coating density of organic phosphonic acid (PA) modifiers. Single-gas, pressure-decay adsorption measurements showed that with a complete n-butylphosphonic acid (BPA) monolayer, the C3H6/C3H8 kinetic selectivity was > 5 initially, and it approached the equilibrium selectivity of similar to 1.2 after 20 min, whereas a coating of 4-phosphonobutyric acid (COOHC(3)PA) with a similar chain length as BPA yielded a selectivity of 15 at 60 min. Coating with 3-aminopropyl phosphonic acid (NH(2)C(3)PA) resulted in high resistance to gas diffusion. To investigate whether the slow adsorption was attributable to excessive NH(2)C(3)PA, the coating density was tuned by varying PA concentration for deposition. As the coating density decreased, the initial adsorption rates increased. With an similar to 0.1 monolayer NH(2)C(3)PA coating, the C3H6/C3H8 kinetic selectivity was > 15 for 60 min. Temperature-programmed desorption of n-propylamine suggested that the improved selectivity of NH(2)C(3)PA coating may be associated with the affinity of the amine group for the zeolite surface. This study demonstrates that gas adsorption rates and selectivities in zeolites are highly sensitive to the composition and density of monolayer films on the external surface.

Aldol condensation of mixtures of acetaldehyde and acetone was investigated over TiO2 catalysts modified with phosphate groups of varying coverages to probe effects of surface composition on reaction selectivity. Whereas the self-aldol condensation of acetaldehyde to crotonaldehyde was observed to dominate on unmodified TiO2, we found that modifying the TiO2 catalyst with surface phosphate groups resulted in improved selectivity toward cross-aldol condensation. Moreover, whereas high phosphate coverages led to lower overall condensation rates, decreasing the density of the phosphate layer resulted in activities on par with the unmodified catalyst, while maintaining higher selectivity. Characterization of reactant binding affinities and the electronic nature of the catalyst using temperature-programmed desorption, diffuse reflectance Fourier transform spectroscopy, and X-ray photoelectron spectroscopy suggested that the changes in selectivity stem from changes in reactant binding driven by the phosphates modifying the electronic nature of the catalyst. This approach represents a promising path toward tuning selectivity for aldol condensation reactions in heterogeneous systems with a relatively facile catalyst modification technique.

The synergistic effects of cosolvent and hydrogen-donor (formate) concentration on Pd-catalyzed transfer hydrogenation of vinylphenol are explored for water and water-alcohol mixtures, with a change in the optimum cosolvent mixture observed for different formate concentrations. The results are interpreted in terms of solvent-based tuning of the formate surface coverage, where an optimal formate coverage is required to facilitate hydrogen transfer without excessively blocking surface binding sites. This interpretation is supported by measurements of the formate surface coverage using adsorption-induced attenuation of self-diffusiophoretic Janus particle motion in water and a water-alcohol solvent. The adsorption isotherms demonstrated tuning of formate surface coverage by the cosolvent, with addition of the alcohol cosolvent increasing formate adsorption. The results contribute to rational solvent selection for transfer hydrogenation reactions and provide insight into the roles cosolvents can play in the design of liquid-phase catalytic reaction systems.

Aluminosilicate materials have been extensively studied as efficient aldol catalysts for C-C coupling reactions due to their acidic nature, high surface area, thermal stability, and porous structure. This work investigated the impact of water vapor pressure on the catalytic reactivity of aluminosilicates for the aldol condensation of propanal to 2-methyl-2-pentenal (MP). The catalytic performance of amorphous SiO2-Al2O3 (A-Si-Al) and aluminated MCM-41 (Al-MCM-41) for the vapor-phase aldol condensation of propanal was evaluated at 200 degrees C as a function of vapor-phase water content at atmospheric pressure. Our findings demonstrate that co-feeding low water vapor pressures (1-18 kPa) with propanal enhances the rates of MP production at 200 degrees C on A-Si-Al. Conversely, water vapor pressures of 25 kPa result in a decrease in aldol dimer formation rates. The rate of MP production evaluated on Al-MCM-41 also increased in the presence of 5 kPa water compared to anhydrous conditions. Propylamine temperature-programmed desorption analyses revealed an increase in Br & Oslash;nsted acid site density when both catalysts were exposed to water, which likely accounts for the observed enhancement in aldol condensation reactivity under hydrous conditions. Reversibility testing of the water vapor effect under reaction conditions, combined with X-ray diffraction analysis of fresh, spent, and regenerated catalysts, revealed no structural changes in either aluminosilicate upon exposure to water or reaction conditions. The rates of aldol condensation and the impact of water vapor were highly consistent across both materials, suggesting that zeolite crystallinity has minimal influence on the catalytic performance.

Selective hydrogenation of acetylene in ethylene-rich streams is important for industrial applications of ethylene and is commonly performed on Pd-based catalysts. To improve the ethylene selectivity, we incorporated highly dispersed Pd into 4A, a Linde type A zeolite with a pore size of similar to 4 & Aring;, with the assistance of mercaptosilanes. Reaction studies indicated that incorporation of Pd within the zeolite (Pd@4A) resulted in higher ethylene selectivity compared to deposition on the external surface of the zeolite (Pd/4A), even at high acetylene conversions near 99%. Pressure decay adsorption measurements showed that diffusion was markedly faster for acetylene compared to ethylene within the 4A. To test the hypothesis that pore (window) size determined selectivity, the Pd@4A zeolite pore size was further modified by variable loadings of NaOH. Breakthrough curve measurements and kinetic adsorption studies indicated that the ethylene diffusion rate decreased with increasing deposition of NaOH, suggesting that accessibility of ethylene to the encapsulated Pd within the LTA zeolite was hindered. The NaOH-modified zeolites exhibited a higher ethylene selectivity (similar to 80% under 93% acetylene conversion). However, excessive NaOH loading led to a low activity. This strategy provides an avenue for enhancing the selectivity by tuning the accessibility of active sites inside of the porous material.

Ceria composite catalysts have long been used for ketonization reactions, which is a valuable chemistry for the upgrading of biomass-derived carboxylates. To better understand the interaction of zirconia with ceria in the context of ketonization, thin epitaxial films of ceria-zirconia mixed metal oxide Ce1-xZrxO2-delta (x = 0-1) were grown on a Pt(111) substrate in ultrahigh vacuum conditions and studied with X-ray photoelectron spectroscopy (XPS). Core level and valence band XPS results suggest a strong interaction between ceria and zirconia cations, possibly due to increased filling of unoccupied 4f0 orbitals of ceria from neighboring Zr cations in the lattice structure. This leads to a partial reduction of ceria from Ce4+ to Ce3+, with Zr remaining predominantly in the 4+ oxidation state. Ketonization of acetic acid was studied using temperature programmed desorption (TPD) and high-resolution electron energy loss spectroscopy (HREELS). These results found ketonization over mixed Ce-Zr composite oxides exhibited lower activation energies than for pure CeO2 and ZrO2, with Ce0.38Zr0.62O2-delta exhibiting the highest yield of acetone among the studied surfaces. These results suggest the high activity of CeZr catalysts appears to be a result of oxygen vacancy formation, stabilized by electron donation from Zr cations.

We report enhanced active particle motion in hydrogen peroxide-fueled self-diffusiophoretic active particle systems of up to 400% via addition of low concentrations of oxygen scavenging agents such as formic acid (as well as other organic acids, hydrazine, and citric acid), whereas active motion was inhibited at higher concentrations. Control experiments showed that enhanced motion was decoupled from catalytic hydrogen peroxide decomposition rate and insensitive to particle surface chemistry. Experimental results point to bulk oxygen scavenging as the cause for the enhanced active motion, representing a realization of recently predicted promotional effects of product sinks on self-diffusiophoretic motion. Diminished active motion at high oxygen scavenger concentrations was attributed to catalytic site blocking by adsorbed solute.

This study investigated the high-intensity focused ultrasound (HIFU)-mediated propulsion of mesoporous silica nanoparticles (MSNs) and microspheres (MSMs). Nanoparticles are heavily sought as vehicles for drug delivery, but their transport through tissue is often restricted. Here, MSNs and MSMs are hydrophobically modified and coated with phospholipids to facilitate inertial cavitation to promote propulsion under HIFU. Modified nanoparticles show significantly enhanced cavitation and propulsion, achieving a maximum displacement of 250 mu m (approximate to 2500 body length) and speed of approximate to 1600 mu m s-1 (16 000 body length s-1), compared to unmodified nanoparticles (2 mu m, 20 body length, 60 mu m s-1, 600 body length). In contrast, microparticles demonstrate comparable cavitation responses. Modified microparticles reached a maximum speed of 4000 mu m s-1 (800 body length s-1) and displacement of 230 mu m (46 body length), and unmodified microparticles achieved 2000 mu m s-1 (400 body length s-1) and 75 mu m (15 body length). In all HIFU-responsive samples, displacement and speed decreased with successive pulses, implying that particles fatigue with continued pulsing. Analyses of particle trajectories and rotational diffusion times suggest that cavitation occurs uniformly on particle surfaces rather than at specific sites. These principles are important for the design of future drug-delivery vehicles capable of ultrasound-triggered motion. High-intensity focused ultrasound (HIFU) is used to propel silica nano- and microparticles through inertial cavitation. Surface modifications dramatically enhance nanoparticle propulsion, but microparticles propel regardless of modification. Nanoparticles reached speeds as high as 16 000 body lengths per second. These insights inform the design of ultrasound-responsive particles for potential drug delivery applications. image

Aldol condensation of mixtures of acetaldehyde, acetone and butanone was investigated over a powder TiO2 catalyst to probe a method for coupling light oxygenates generated from biomass pyrolysis into heavier, higher-value products. Self-aldol condensation (SAC) of each component was found to produce the expected dimers (e.g., crotonaldehyde from acetaldehyde, mesityl oxide from acetone) and higher molecular weight products formed from multiple coupling reactions. Mixed-aldol condensation (MAC) reactions for acetaldehyde, acetone, and butanone yielded the same products as well as cross-condensation products such as 3-penten-2-one. In MAC reactions, acetaldehyde suppressed the reaction of the other species in the mixture, such that in low-conversion reactions with equimolar feeds, crotonaldehyde dominated product selectivity. Kinetic experiments conducted with variable partial pressures of the reactants indicated a higher dependence of reactions rates on the pressures of acetone and butanone compared to acetaldehyde, consistent with a difference in the saturation of catalytic active sites between reactant molecules. Infrared spectroscopy experiments after pyridine chemisorption showed that acetaldehyde SAC reactions decreased Lewis acid site availability more quickly than acetone SAC reactions. Results from kinetic and temperature programmed desorption studies indicated that the higher rates for acetaldehyde conversion could be attributed to both its tendency to out-compete acetone for access to adsorption sites and its effectiveness as an electrophile.

Reductive catalytic fractionation (RCF) is a promising method to extract and depolymerize lignin from biomass, and bench-scale studies have enabled considerable progress in the past decade. RCF experiments are typically conducted in pressurized batch reactors with volumes ranging between 50 and 1000 mL, limiting the throughput of these experiments to one to six reactions per day for an individual researcher. Here, we report a high-throughput RCF (HTP-RCF) method in which batch RCF reactions are conducted in 1 mL wells machined directly into Hastelloy reactor plates. The plate reactors can seal high pressures produced by organic solvents by vertically stacking multiple reactor plates, leading to a compact and modular system capable of performing 240 reactions per experiment. Using this setup, we screened solvent mixtures and catalyst loadings for hydrogen-free RCF using 50 mg poplar and 0.5 mL reaction solvent. The system of 1:1 isopropanol/methanol showed optimal monomer yields and selectivity to 4-propyl substituted monomers, and validation reactions using 75 mL batch reactors produced identical monomer yields. To accommodate the low material loadings, we then developed a workup procedure for parallel filtration, washing, and drying of samples and a H-1 nuclear magnetic resonance spectroscopy method to measure the RCF oil yield without performing liquid-liquid extraction. As a demonstration of this experimental pipeline, 50 unique switchgrass samples were screened in RCF reactions in the HTP-RCF system, revealing a wide range of monomer yields (21-36%), S/G ratios (0.41-0.93), and oil yields (40-75%). These results were successfully validated by repeating RCF reactions in 75 mL batch reactors for a subset of samples. We anticipate that this approach can be used to rapidly screen substrates, catalysts, and reaction conditions in high-pressure batch reactions with higher throughput than standard batch reactors.

Chemical recycling of end-of-life plastic wastes through hydrogenolysis is a promising pathway for achieving a circular plastics economy and reducing overall energy costs. Understanding molecular interactions at the inorganic-organic depolymerization interface is crucial for enhancing catalyst performance and overcoming challenges posed by mixed plastic waste streams. We investigated a fundamental step in the depolymerization process: physisorption of polymers onto the metal oxide support preceding diffusion to and reaction at the catalyst-support junction. Molecular dynamics simulations, augmented with well-tempered metadynamics, were conducted to explore the adsorption of polylactic acid (PLA) and polyethylene terephthalate (PET) oligomers onto a hydroxylated alumina support surface. Our findings revealed multiple layers of highly oriented solvent molecules (1,4-dioxane) above the surface, creating significant barriers to polyester adsorption. Disrupting and displacing these solvent layers led PET oligomers to adsorb closer to and interact stronger with the surface than PLA oligomers, possibly contributing to the higher reaction temperatures needed to achieve full conversion in PET versus PLA hydrogenolysis. We further suggest an experimental approach to validate our results of solvent layering behavior through predictions of X-ray reflectivity that are consistent with our initial experiments. The insights gained in this study can be leveraged to refine our understanding of catalytic mechanisms to predict depolymerization reactivity and selectivity and improve future hydrogenolysis catalyst designs.

Aldehydes are selectively oxidized to carboxylates on group 11 metals at low potentials (<0.4 V vs. RHE) in alkaline media. This process can occur by a pathway that generates H2 gas from the aldehyde, known as electro-oxidative dehydrogenation (EOD) or anodic hydrogen production. The EOD process occurs with transfer of only one electron per aldehyde, whereas typical oxidation with discharge of hydrogen to form water is a two-electron process. Here, we study the catalytic activity and selectivity toward H2 of Au, Ag, and Cu electrodes using benzaldehyde with rotating disk and ring-disk electrode (RDE/RRDE) techniques. The average number of electrons per benzaldehyde molecule obtained via H2 detection by RRDE agrees with that obtained via Koutecký-Levich analysis conducted at various rotation rates. We find that Au and Ag have much higher H2 and benzoate formation rates than Cu, but that Cu can perform the reaction at about 0.2 V lower overpotentials. On all three materials, benzaldehyde oxidation has high selectivity to anodic H2 (one-electron pathway) below ~0.5 V vs. RHE, but, with increasing potential, the selectivity shifts to H-oxidation forming water (two-electron pathway).

Phosphonic acid (PA) self-assembled monolayers (SAMs) were deposited onto Pt/Al2O3 catalysts to modify the support to enable control over CO2 adsorption and CO2 hydrogenation activity. Significant differences in catalytic activity toward CO2 hydrogenation (reverse water-gas shift, RWGS) were observed after coating Al2O3 with PAs, suggesting that the reaction was mediated by CO2 adsorption on the support. Amine-functionalized PAs were found to outperform their alkyl counterparts in terms of activity, however there was little effect of amine location in the SAM (i. e., spacing between the amine functional group and phosphonate attachment group). One amine-PA and one alkyl-PA, aminopropyl phosphonic acid (C(3)NH(2)PA) and methyl phosphonic acid (C(1)PA), respectively, were investigated in more detail. The C(3)NH(2)PA-modified catalyst was found to bind CO2 as a combination of carbamate and bicarbonate. Additionally, at 30 degrees C, both PAs were found to reduce CO2 adsorption uptake by approximately 50 % compared to unmodified 5 %Pt/Al2O3. CO2 adsorption enthalpy was measured for the catalysts and found to be strongly correlated with hydrogenation activity, with the trend in binding enthalpy and CO2 hydrogen rate trending as uncoated >C(3)NH(2)PA>C(1)PA. PA SAMs were found to have weaker effects on CO binding and CO selectivity, consistent with selective modification of the Al2O3 support by the PAs.

Controlling reactant adsorption on catalyst surfaces is crucial to reaction activity and selectivity. One method for improving selectivity is by imposing steric constraints to bias the reactant binding orientation. In this study, thiol self-assembled monolayers (SAMs) were deposited onto Pt/Al2O3 catalysts as a method for controlling activity and selectivity via steric effects. In addition to a full monolayer, a low-density SAM-coated catalyst was employed. A number of characterization techniques demonstrated the successful deposition of homogeneous low-density SAMs on the metal surface with reduced site-blocking compared to a full high-density monolayer. Reaction kinetic studies showed increased benzyl alcohol hydrodeoxygenation (HDO) selectivity for both SAM-modified catalysts. This was attributed to the inability of the reactant to adsorb on the catalyst with the aromatic ring parallel to the surface, thus preventing decarbonylation and ring hydrogenation reaction pathways. Additionally, SAM density influenced reaction activity significantly, with the low-density-modified SAM catalyst being more active than the catalyst coated with a full monolayer. Moreover, liquid-phase hydrogenation reactions were used to investigate the relationship between SAM density and reactivity for reactant molecules of various sizes. In all cases, the low-density SAM improved reaction rates relative to dense SAMs. The effect of controlling ligand density depended on the type of reaction: high ligand densities greatly diminished ring hydrogenation, while HDO was largely unaffected, suggesting a potential strategy for size-selective reaction rate and selectivity control.

Phenolic moieties strongly influence lignin reactivity and physical properties, and thus accurate quantification of phenolic groups in lignin is a critical analytical chemistry need. Today, 31P nuclear magnetic resonance (NMR) spectroscopy is widely considered the standard method to this end, but this approach uses a hazardous and expensive derivatization agent, and the NMR spectroscopy experiments are time consuming due to long relaxation times. Here, we report a complementary method that enables accurate identification and quantification of phenolic groups in lignin samples using pentafluoropyridine (PFP) as a derivatizing reagent followed by 19F NMR spectroscopy. Using dimethyl sulfoxide as a solvent in the presence of K2CO3, phenolic hydroxyl groups in lignin model compounds were fully converted to the corresponding tetrafluoropyridyl-ether products within 1 min. PFP exhibits high selectivity for the reaction with phenolic hydroxyl groups relative to aliphatic alcohols, and we show that side reactions with carboxylic acids, if present, can be avoided through the addition of 40% water to the reaction solvent. The PFP 19F method achieved similar results compared to 31P NMR spectroscopy when applied to reductive catalytic fractionation oil from poplar, softwood kraft lignin, and corn stover milled wood lignin, thereby offering a safe and cost-effective method for phenolic measurements in lignin.

The adsorption strengths of organic compounds on metal surfaces are sensitive to the metal composition, and they play a central role in many catalytic reactions, helping to control the coverage of the reactant and altering the overall reaction rate. While adsorption energies are straightforward to measure and calculate in vacuum and gas-phase environments, adsorption energetics can be dramatically altered by the presence of solvent in liquid-phase reactions. However, the effects of metal composition on binding strengths in a liquid environment are less well understood, primarily due to the difficulty of accurate in situ measurements of organic binding on metal surfaces in the liquid phase. Here, we utilize the motion of active particles in water to probe the adsorption energies of an organic adsorbate (furfural) on a range of metal surfaces (pure Pd, pure Pt, and four PdAu alloy compositions) to elucidate the effect of metal composition. Janus particles with catalytic caps of particular metal compositions all exhibited active motion resulting from consumption of H2O2; adsorbate binding was inferred through the decrease in the velocity of active motion and was modeled by a Langmuir adsorption isotherm. The measured adsorption affinities were used to extract the adsorption enthalpy of furfural on the different metals. The Pd surface was found to bind furfural more strongly than the Pt surface by some 10 kJ/mol. Furthermore, the adsorption of furfural on the alloys was found to increase monotonically in magnitude with Pd content. The data reported herein aid the development of accurate understanding of organic adsorption in the presence of solvent and the role of the metal surface in tuning adsorption strengths to optimize catalytic processes in the liquid phase.

Self-assembled monolayers (SAMs) of thiolates have increasingly been used for modification of metal surfaces in electrochemical applications including selective catalysis (e.g., CO2 reduction, nitrogen reduction) and chemical sensing. Here, the stable electrochemical potential window of thiolate SAMs on Au, Pt, and Cu electrodes is systematically studied for a variety of thiols in aqueous electrolyte systems. For fixed tail-group functionality, the reductive stability of thiolate SAMs is found to follow the trend Au < Pt < Cu; this can be understood by considering the combined influences of the binding strength of sulfur and competitive adsorption of hydrogen. The oxidative stability of thiolate SAMs is found to follow the order: Cu < Pt < Au, consistent with each surface's propensity toward surface oxide formation. The stable reductive and oxidative potential limits are both found to vary linearly with pH, except for reduction above pH ∼10, which is independent of pH for most thiol compositions. The electrochemical stability across different functionalized thiols is then revealed to depend on many different factors including SAM defects (accessible surface metal atom sites decrease stability), intermolecular interactions (hydrophilic groups reduce the stability), and SAM thickness (stability increases with alkanethiol carbon chain length) as well as factors such as SAM-induced surface reconstruction and the ability to directly oxidize or reduce the non-sulfur part of the SAM molecule.

Oxidative conversion of biomass-derived compounds to value-added chemicals is challenging due to the tendency of multi-functional reactants to overoxidize. Catalyst performance can be sensitive to both synthesis and pretreatment conditions. Additionally, coating the catalyst with self-assembled monolayers (SAMs) has shown promise in modulating activity and selectivity. Here, the liquid-phase partial oxidation of glutaraldehyde (GA) to glutaric semialdehyde (GSA) was investigated as a model reaction using a Pd/Al2O3 catalyst, with and without various thiolate SAM modifiers. Reductive pretreatment of the catalyst showed enhancement in the activity and a shortening of an apparent induction period relative to the untreated catalyst. The selectivity for GSA was further found to be sensitive to the identity of the SAM layers, with hydrophilic thioglycerol (TG) and thiolactic acid (TLA) coatings showing an enhancement in selectivity to GSA; the TG coating raised selectivity from - 60 % (on uncoated catalyst and catalysts coated with hydrophobic thiols) to - 80 % at identical conversion (- 30 %). However, the TG coating exhibited lower catalytic rates compared to UC and hydrophobically coated materials. Morphological and electronic causes were ruled out with various materials characterization techniques. Density functional theory (DFT) calculations suggested that hydrogen bonding stabilizes adsorption of GSA compared to the uncoated Pd surface. However, a large stabilization of glutaric acid (GAC) adsorption for TG-coated Pd was also predicted, likely leading to accumulation of this overoxidation product and lower overall rates. Inhibition of the rate of GA partial oxidation by GAC adsorption was then corroborated experimentally. Finding ways to stabilize the less-oxidized intermediates with more specificity is thus suggested as a strategy to improve rate and selectivity.

We investigate how four different processing routes influence the grain boundary chemistry of the proton-conducting oxide BaZr 0.9 Y 0.1 O 3− δ (BZY10) via atom probe tomography (APT). Differing processing routes can cause large variations in GB chemistry.

We used a combination of experimental spectroscopies, density functional theory calculations, and CO2 hydrogenation studies to investigate the effects of modifying single-atom Rh-1/TiO2 catalysts with functionalized phosphonic acid monolayers. We found that the deposition of specific amine-functionalized ligands resulted in an similar to 8x increase in site-specific CO2 reduction turnover frequency at 150 degrees C and a similar to 2x increase at 250 degrees C. On-stream stability also improved following ligand deposition. The effect of the modifier on reactivity was highly sensitive to the proximity of the amine functional group to the surface, which was controlled by adjusting the length of the phosphonic acid tail. Furthermore, deposition of alkyl phosphonic acids without an amine functional group resulted in blocked CO2 adsorption and a near-complete loss of catalytic activity. Infrared spectroscopy studies suggested that the amine group provided binding sites for CO2 that enabled hydrogenation when the amine was positioned near a Rh-1 site. Phosphonic acid-modified catalysts also exhibited high selectivity to CO over the series product methane; the selectivity effect was traced to modification of the Rh-1 sites to favor CO desorption. Phosphonic acid deposition resulted in 80-90% loss of accessible Rh-1 sites, likely due to blocking by tail groups. However, even with the loss of sites, under low-temperature reaction conditions, the rates of CO2 hydrogenation were improved with the coatings, indicating that the remaining sites are highly efficient. Organic functionalization of the supports for atomically dispersed catalysts offers the opportunity to precisely control the positioning of functional groups in the vicinity of a well-defined active site, potentially enabling an additional level of control over active site design.