Additive-mediated interfacial engineering of H_2SO_4-catalyzed isobutane alkylation from molecular design to industrial process intensification

Domain: biology
Published: 2026-03-21
Editorial outcome: minor_revision

Abstract
Understanding and correlation of the multiscale interfacial mass transport behaviors mediated by the additive for liquid/liquid dispersion system is challenging. Here, we propose interfacial mass transfer flux through the quantitative coupling between microscopic interfacial parameters and mesoscopic droplet mass transfer model for H SO -catalyzed isobutane alkylation with emphasis on additive molecular design to industrial process intensification. Microscopic interfacial parameters are incorporated into CFD-PBM model to determine interfacial mass transfer flux of isobutane (N ). Based on the ratio of N in the system with and without the additives, the interfacial enhancement factor E is proposed and validated as an indicator for optimal additive screening. Decoupled N from apparent kinetic model, mass transfer-free kinetic parameters of isobutane alkylation are determined, quantitatively confirming the reaction is mass transfer controlled. Additive-mediated process intensification reveals PPG400 additive increases alkylate capacity by 24.85% up to 99.83 kt/a from 79.96 kt/a in additive-free system.

Introduction
Immiscible liquid-liquid interfacial reactions exhibit distinct energetic states and organizational behaviors compared to those in the bulk phases1,2,3,4. The interfacial intensification of the liquid-liquid systems mediated by amphiphilic additives is a noteworthy development, which has emerged as a promising technique in the oil recovery5, pharmaceutical production6, and solvent extraction7, primarily because of increased Marangoni convection and enhanced interfacial mass flux8,9,10,11. A typical case of heterogeneous liquid-liquid interfacial reaction is the isobutane alkylation with C3-C5 olefins under conditions of strong acid (H SO ) and intense shear forces to generate C alkylate product, where numerous rapid reactions and mass transport take place simultaneously at the acid/hydrocarbon interfacial regions12, 13. The promising green catalysts such as ionic liquids (ILs) have been extensively investigated, yet remain challenging due to high operating costs, difficult disposal of spent salts, and insufficient stability under industrial operating conditions. In contrast, concentrated H SO -catalyzed isobutane alkylation still represents the dominant industrial process, owing to its high stability and excellent catalytic performance. Due to the polarity difference, the nonpolar isobutane exhibits lower solubility in the acid phase and undergoes slower diffusion across the acid/hydrocarbon interface compared to butene, and thus the interfacial mass transfer of isobutane is the rate-determining step for the isobutane alkylation14,15,16. Over the past decades, the high ratio of isobutane to olefins (I/O ratio>8) in feedstock and the inadequate mixing between C4 hydrocarbons phase and H SO phase have seriously hindered the further increase in the capacity of a single reactor of the H SO -catalyzed isobutane alkylation17,18. Alternatively, the introduction of intensified additives (e.g., ionic liquids, deep eutectic solvents, surfactants, etc.) proved to be one of the promising ways to reduce the interfacial tension, promote the bi-phase mixing, increase the interfacial I/O ratio, inhibit the butene oligomerization, and thus improve the quality and capacity of alkylate, which has attracted considerable attentions19,20. However, the quantitative correlations of the additive-intensified behaviors for the H SO -catalyzed isobutane alkylation from microscale interfacial properties to mesoscale mass transfer behaviors and to industrial process intensification still remain greatly ambiguous.

The prerequisite to bridge the gap between the microscale interfacial properties to mesoscale mass transfer behaviors and to industrial process intensification for the isobutane alkylation relies on the estimation of the isobutane mass transfer across the acid/hydrocarbon interface to quantify how it tunes the multiscale transport behaviors and related kinetics. From the mesoscale perspective, the utilization of the electro microscope, clear photos of the isobutane mixing with catalytic systems found that the addition of ammonium surfactant can significantly decrease droplet size and enhance the dispersion of isobutane21, which mainly arises from the improvement of trace additives on the microscale interfacial properties at liquid/liquid acid/hydrocarbon interface of H SO -catalyzed isobutane alkylation22,23. At the molecular scale, furthermore, the understanding of interfacial properties altered by additives (e.g., ionic liquids, deep eutectic solvents, and surfactants) has been considerably investigated to elucidate the interfacial transport behaviors of isobutane using molecular dynamics (MD) simulation 24,25,26. It is found that additives with long-chain and organic aromatic structures have a propensity to align perpendicularly to the interface, which is conducive to their accumulation at the interface, thereby enlarging the interfacial thickness (σ), reducing the interfacial tension (𝛾), and giving rise to the different mesoscopic mass transport behaviors and kinetics27,28. These behaviors and kinetics are also influenced with respect to the proportion of the dispersed phase, mechanical mixing conditions, physicochemical characteristics of reactants and catalyst, and reactor geometry29,30,31,32. Recently, according to the volume of fluid (VOF) model, the flow behaviors of hydrocarbon phase in the acid phase for H SO -catalyzed isobutane alkylation were investigated in detail, which indicates strong vortices can accelerate surface renewal and significantly enhance the mass transfer of isobutane16,20, but the effect of the additive on the interfacial behaviors was not considered33.

Despite the considerable microscale and mesoscale investigations for the H SO -catalyzed isobutane alkylation, there is a large gap in the quantitative correlation between the microscale interfacial properties and mesoscale droplet dispersion behaviors. Fortunately, obtaining microscopic key interfacial parameters and further combining them with the mesoscopic flow behaviors to obtain interfacial mass transfer flux (N ) could potentially allow to bridge the gap for the quantitative correlation between the microscale interfacial properties and mesoscale droplet dispersion behaviors, and simultaneously quantitatively evaluate the enhancement effect of additives on the acid/hydrocarbon interfacial properties of H SO -catalyzed isobutane alkylation.

In addition, reliable kinetic parameters are essential for fundamentally assessing whether additives facilitate the crucial steps in alkylation reactions34,35. These reactions are extremely complex, involving simultaneous pathways such as alkylation, polymerization, cracking, disproportionation, and self-alkylation, which proceed via carbonium ion intermediates36,37,38. Early efforts have systematically studied the apparent kinetics of additive-mediated alkylation systems to elucidate the formation pathways of key components, including trimethylpentanes (TMPs), dimethylhexanes (DMHs), and heavy ends (HEs, C +) in alkylate39. Moreover, the increased selectivity of TMPs components observed in systems with additives like [N ][C SO ] is attributed to an increased rate constant for hydride transfer from isobutane to TMPs cations, a phenomenon linked to accelerated mass transfer of isobutane40. However, these apparent kinetic parameters are inherently confounded by mass-transfer effects under varying conditions, which cannot isolate and accurately quantify the transport enhancement solely attributable to the additive, making direct comparisons unreliable and hindering the establishment of a theoretical basis for rational screening of additives. To address this challenge, this study aims to develop a mass transfer-free kinetic model that decouples chemical reaction rates from mass-transfer limitations, thereby providing a more robust framework for evaluating additive efficacy from the perspective of kinetics.

In this work, we proposed an interfacial mass transfer flux through the quantitatively coupling between the microscopic interfacial parameters and mesoscopic droplet mass transfer model of the liquid/liquid dispersion system of H SO -catalyzed isobutane alkylation with emphasis on the additive molecular design to the industrial process intensification based on the complex reaction/mass transfer coupling kinetics (Fig.1). Firstly, for the H SO -catalyzed isobutane alkylation system with non-ionic additives and ionic amphiphilic additives at controlled interface coverage as well as varying temperature, three representative microscopic interfacial parameters, including 𝛾, c*, and diffusion coefficients (D) were determined, underscoring the role of additives in regulating interfacial properties. Upon incorporating the microscopic interfacial parameters into the mesoscopic liquid-liquid mass transfer model, the simulated droplet size distribution, specific surface area (a), mass transfer parameters (k , k a), and crucial N were determined by CFD-population balance model (PBM) simulation and semi-empirical formula calculation, respectively. Thereafter, based on the ratio of N in the system without and with the additives, the interfacial enhancement factor (E) was proposed as an indicator to quantitatively assess the mass transfer intensification degree of isobutane. Significantly, it shows good agreement with macroscopic enhanced catalytic performance in the isobutane alkylation systems with diverse additives. In particular, by leveraging the N into the apparent kinetic models of isobutane alkylation to decouple the rate-determining step of isobutane mass transfer, mass transfer-free reaction rate constants of the isobutane alkylation were obtained, and the activation energies of the ultrafast hydride ion transfer reactions were calculated. Furthermore, the kinetic parameters were inserted into the process simulation to predict the additive-intensified industrial C4 alkylation process, which predicts the production capacity of alkylate with propylene glycol with a molecular weight of 400 (PPG400) additives can be increased by about 24.85% up to 99.83 kt/a from the typical 79.96 kt/a in the additive-free system for the typical industrial alkylation unit. The strategy we proposed not only deepens the comprehension of additive-intensified isobutane alkylation but also has a great potential to be extended into more liquid-liquid heterogeneous systems from microscale properties to macroscale process optimization.

Results
Effects of PPG400 additive on microscale acid/hydrocarbon interfacial properties

Initially, PPG400 was selected as the surfactant additive for the reaction reinforcement due to the numerous advantages, such as low price, no halogen and metallic elements, and reactive functional groups at the terminal sites41, 42. Considering the enrichment of additives at the interface can alter the physical properties and concentration gradients to a large extent, detailed interfacial properties for the H SO -catalyzed isobutane alkylation system without and with PPG400 additive at different interface coverage and temperature was initially studied via MD simulations with the optimized structures of each moiety shown in Supplementary Fig. 1. The equilibrated snapshots and mass density profiles along the z-axis of PPG400 distribution at various concentrations across the acid/hydrocarbon interface for H SO -catalyzed isobutane alkylation are presented in Fig. 2a. The PPG400 molecules tend to accumulate at the acid/hydrocarbon interface (Supplementary Figs. 2-4) exhibiting a distinct peak in the interfacial regions, and the distribution of 2-butene is closer to the acid phase compared to isobutane. In particular, the interfacial coverage is defined as the number of PPG400 molecules per interfacial area (molecule/nm2)29. As the interfacial coverage of the PPG400 additive increases, the intensity of this peak rises significantly (Supplementary Fig. 4). The orientation of the long carbon chains of PPG400 towards the acid phase enables a more substantial penetration of C4 hydrocarbons into the interface (Supplementary Fig. 3).

To fully elucidate the effect of PPG400 additive on the regulation of microscopic interfacial transport, the interfacial tension (𝛾) and interfacial thickness (σ) for the PPG400-aiding system as a function of interfacial coverage were further studied (Fig. 2b and Supplementary Note 1-2). σ is positively correlated with interfacial coverage, whereas 𝛾 exhibits an inverse relationship. Specifically, 𝛾 and σ of the fresh H SO system are 26.20 mN/m and 0.24 nm, respectively. Upon incorporation of PPG400, as the interfacial coverage increases from 0.028 to 0.194 molecule/nm2, 𝛾 decreases from 26.17 mN/m to 24.95 mN/m, while σ rises from 0.254 nm to 0.328 nm (Fig. 2b and Supplementary Fig. 5). Consequently, the PPG400 additive reduces 𝛾 and concurrently enhances σ compared to the additive-free system.

On the other hand, the microscopic interfacial parameters, including interfacial isobutane concentration difference between the interface and the acid phase (∆c *) and D of isobutane, altered by the addition of PPG400, were quantified. ∆c*, identified as the key mass transfer driving force in H SO -catalyzed alkylation (Fig. 2c and Supplementary Note 3), is significantly higher than that of the fresh H SO system. Notably, ∆c * reaches a maximum value of 4.81×10-3 mol/kg at the interfacial coverage of 0.055 molecule/nm2, equivalent to the PPG400 concentration of 0.3 wt%. The effect of PPG400 coverage on ∆c * presents a trade-off relationship. At moderate coverage, PPG400 can enrich the isobutane at the interface by optimizing thermodynamic driving forces, whereas excessive coverage introduces larger steric hindrance, causing a slight decline in ∆c *. Concurrently, the D of C4 reactants across the interface as a function of interfacial coverage was calculated (Supplementary Note 4 and Fig. 2c). Compared to the additive-free system, existence of PPG400 at the interface restricts the isobutane diffusion, reducing D to a minimum value of 0.115×10-10 m2/s at the highest interfacial coverage. This suppression of interfacial dynamics is primarily attributed to the increased σ, which elongates the diffusion path for isobutane molecules and imposes transport limitations due to interfacial blocking by the long chains of PPG400. To quantitatively assess the thermodynamic standard free energy of key isobutane molecule, the potential of mean force (PMF) of isobutane was calculated under varying PPG400 concentrations (Supplementary Note5 and Table 1). The interfacial PMF difference (ΔPMF), defined as the energy barrier for isobutane transfer from the interface to the acid phase, decreases markedly from 35.40 kJ/mol in the fresh H SO system to a minimum of 28.92 kJ/mol at 0.3 wt% PPG400. This reduction reveals a significantly lowered mass transfer resistance, since the additive accumulates at the interface and improves its properties to favor the isobutane penetration.

In addition, the elevated temperature decreases the 𝛾 from 26.92 mN/m to 25.60 mN/m, while increasing the σ from 0.253 nm to 0.279 nm (Fig. 2d). This interfacial remodeling is driven by intensified molecular dynamics, which enhances hydrocarbon penetration across the phase boundary. Consequently, the D of isobutane rises significantly (Fig. 2e). The accelerated diffusion promotes rapid equilibration, which shortens the residence time of isobutane at the interface and thereby suppresses the buildup of a high concentration gradient, leading to a decrease in ∆c * (Fig. 2e).

It should be noted that the simulated I/O ratio is 16:1 for MD simulations, which is the same as the following experimental alkylation conditions. To eliminate significant differences in isobutane and butene concentration, MD simulations are also conducted under a 1:1 I/O ratio. Significantly, the interface properties with 1:1 I/O ratio (Supplementary Figs. 6-10) are aligned with those observed in the system with 16:1 I/O ratio, confirming the reliability of the MD simulation results.

Quantitative correlation of microscale interfacial characteristics with mesoscale mass transfer coefficients

According to the above MD simulations, the effects of the additive on microscopic interfacial thermodynamics and dynamics properties are well explained, but such efforts remain inadequate to clarify the mechanism of additive-mediated isobutane mass transfer enhancement at the mesoscopic scale. Mesoscale N is an effective and reasonable parameter for quantifying the amount of isobutane entering the acid phase via interfacial mass transfer. Upon incorporating the microscopic interfacial parameters (D, 𝛾, ∆c *) without and with the PPG400 additive at different concentrations into the mesoscopic droplet mass transfer model (Supplementary Note 6), the hydrocarbon droplet diameter (d ), specific surface area (a), mass transfer parameters (k , k a), and N in the corresponding system can be determined by semi-empirical heterogeneous droplet mass transfer model and CFD-PBM simulations based on the same size of the batch experimental alkylation reactor with the actual dimensions. For each simulation case, the d and hydrocarbon volume fraction were allowed to fully converge to an equilibrium state prior to data acquisition, ensuring that the reported results are representative of steady state conditions (Supplementary Fig. 11).

In isobutane alkylation processes, the hydrocarbon phase, acting as the dispersed phase, is sheared into droplets in the acid continuous phase. Evidently, butene is rapidly and completely oligomerized within seconds of mixing, and the isobutane mass transfer across the droplet interface is the determining step for the alkylation43, 44. Under certain operating conditions, the rate of energy dissipation (ε), dispersed phase dispersion rate (ϕ), and physical properties such as viscosity (μ), density (ρ), stirrer geometry, and reaction conditions are all fixed. Only the microscopic interfacial properties (D, 𝛾, ∆c *) mediated by additives have an impact on the mesoscale mass transfer. The decrease of 𝛾 induced by the incorporation of PPG400 permits the dispersed droplets with smaller d , which means the enlarged a of hydrocarbon phase (Fig. 3a and 3d, and Supplementary Fig. 12). As the dosage of the PPG400 increases, the d distribution shifts toward smaller values and render spatial distribution as homogeneous as possible (Supplementary Fig.13). This phenomenon improves the mesoscopic dispersion efficiency between hydrocarbon phase and acid phase for isobutane alkylation, all of which exert a positive effect on the alkylation process. While the value of k exhibits a continuous downward trend first and then almost remains unchanged as the PPG400 concentration increases (Supplementary Fig. 14), which is consistent with the variation of the microscopic D restricted by the interfacial hindrance effect of the additive. The overall mass transfer coefficient (k a), determined by k and a, first decreases from 0.424 s-1 to 0.421 s-1 as the dosage of the PPG400 increases from 0.1 to 0.6 wt%, and then increases to 0.430 s-1 as the dosage of the PPG400 further increases to 1.0 wt% (Fig. 3b and 3e). Generally, the values of k a in liquid-liquid heterogeneous reactors are between 0.1 and 100 s−1, which proves that the obtained values of k a for the H SO -catalyzed isobutane alkylation are within a reasonable range45,46.

Integrating multiple parameters (k a, ϕ, ∆c *), a quantitative N can be acquired using the following equation:

N =k a (c* -c* )=k a Δc* (1)

where ϕ is the fraction of the dispersed phase, as a constant (Supplementary S10). Based on the semi-empirical calculated results of N distribution in Figs. 3c and 3f, it is observed that the addition of the PPG400 additive significantly promotes the distribution shift of N in the alkylation reactor toward higher magnitudes, compared to the additive-free system. Specifically, at a dosage of 0.3 wt%, the N value reaches a peak of 0.121 mol/kg, corresponding to the most remarkable enhancement of mass transfer of isobutane. Moreover, comparison of the semi-empirical calculated results with those from CFD-PBM simulations (see Fig.3a-c and Supplementary Fig. 13-14) shows that the d , a, k , k a, and N data fall within a 5% error margin, confirming the reliability of the semi-empirical calculated results.

Furthermore, a multi-scale validation framework was established, in which CFD-PBM simulations under varying interfacial tension conditions were used to predict key parameters d and a. Values predicted by the CFD-PBM model show excellent agreement with calculations from semi-empirical formulas that incorporate microscopically derived parameters from following 35 distinct ILs additive systems (Supplementary Fig. 15-17). And a model experiment was designed using the pendant drop method to verify the water/n-octane interfacial tension reduction caused by PPG400 additive in heterogeneous liquid-liquid system (Supplementary Fig. 18 and Table 2).

Correlation of interfacial mass transfer flux with reaction performance

PPG-based additives were employed to experimentally explore the effects of molecular weight, additive amount, reaction time, and temperature on the H SO -catalyzed isobutane alkylation (Supplementary Fig. 19-20 and Table 3). Research octane number (RON) is derived from the proportion of alkylate components and correlates with the changes in selectivity of C components and improved performance47. Among PPG with various molecular weights of 200 to 1500, PPG400 shows the best catalytic performance with the highest yield of C components (Supplementary Fig. 20). The effects of the PPG400 concentration on the alkylate components (Fig. 4a) as well as C components (Supplementary Fig. 21) in fresh H SO systems were investigated. As the dosage of PPG400 increases from 0.1 wt% to 0.3 wt%, the RON and C components show a marked increase from 96.40 to 97.07 and 77.66 wt% to 81.37 wt%, respectively, with the 2,2,4-TMP and 2,3,3-TMP components reaching the maximum values of 29.98 wt% and 22.45 wt%, respectively. However, excessive PPG400 concentration facilitates butene oligomerization and the generation of by-products, with the maximum content of HEs components up to 11.18 wt% at the amount of 1.0 wt%. Furthermore, a lower reaction temperature leads to further improvement in the quality of alkylate with higher selectivity of targeted TMPs components (Fig.4b and Supplementary Fig. 22). The effects of the fresh H SO with and without PPG400 on the alkylate components as a function of reaction time were investigated, as depicted in Supplementary Fig. 23. Upon the addition of PPG400 at the optimized dosage of 0.3 wt%, the alkylate RON is 94.97 at 5 min, and 96.97 at 10 min, versus 90.36 at 5 min and 92.36 at 10 min in the fresh H SO system, respectively, which reveals that PPG400 plays an important role in accelerating the reaction rate.

In particular, a dimensionless parameter, the interfacial enhancement factor E, representing the enhanced degree of the N , was constructed to quantitatively evaluate the impact of additive-mediated microscopic interfacial regulation on mesoscopic mass transfer. E can be derived using Equation (2).

𝐸= (k a) (Δc* ) / (k a) (Δc* ) (2)

where (k a) and (∆c *) are the mass transfer coefficient and interfacial concentration difference of isobutane in the additive-free system, and (k a) as well as (∆c *) are those in the additive-adding system. Notably, the variation trends of the parameter E and macroscopic enhanced catalytic performance in the systems with different PPG400 concentrations were in complete alignment (Fig. 4c). At the optimal dosage of 0.3 wt%, the parameter E attains a peak value of 1.14, corresponding to the most significant enhancement in alkylate RON. Similarly, parameter E calculated by substituting the microscopic interfacial parameters obtained from I/O ratio of 1:1 MD model with different PPG400 concentrations into the empirical formula, agreed well with the macroscopic enhanced catalytic performance of the corresponding PPG400-aiding systems (Supplementary Fig. 24). This concordance robustly demonstrates that E is invariant to the macroscopic I/O ratio, thereby serving as a reliable descriptor exclusively capturing the interfacial mass transfer enhancement induced by additive. To sum up, the introduction of the PPG400 can markedly enhance the acceleration of N , thereby inhibiting the oligomerization of butene and shortening residence time for isobutane alkylation, which can benefit the alkylate quality36.

Generally, the formation of key alkylate components (e.g., TMPs, DMHs) proceeds via instantaneous hydride ion transfer from an isobutane molecule to a larger carbonium ion intermediate (e.g., TMAPs⁺, DMHs⁺), in which mass transfer of isobutane to the acid phase is the rate-determining step, effectively controlling the overall rate of the alkylation process. The apparent kinetic model based on C4 alkylation reaction pathway (Fig. 4d) is initially fitted. To avoid overfitting, the simplified model is used48 (details in Supplementary Notes 7-8 and Supplementary Fig. 25). The apparent kinetics is actually a comprehensive reaction that integrates both the reaction itself and the mass transfer of isobutane. The limiting steps relevant to the mass transfer of isobutane are mainly associated with key rate constants to generate TMPs, DMHs, and HEs, including k , k , k , and k , which within the apparent kinetic model remain susceptible to alterations regulated by the mass transfer of isobutane39,48.

Apparent kinetic model accurately predicts the concentration variations of key alkylate components (Supplementary Notes 7-8 and Supplementary Figs. 26-28), enabling the determination of detailed kinetic constants. For the kinetic parameters k and k in the apparent kinetic model, as the dosage of PPG400 rises from 0.1 wt% to the optimal 0.3 wt%, the value of k relative to the generation of TMPs components varies from 1.35 to 1.75 kg/(mol·min). However, upon excessive addition of PPG400, reaching up to 1.0 wt%, the value of k diminishes to 1.60 kg/(mol·min). Notably, the remaining kinetic parameters relative to hydride ion transfer demonstrate the same tendency (Supplementary Tables 4-6). Notably, the k and k for TMPs and DMHs, respectively, show a good agreement as the enhancement factor E (Fig. 4e). The positive correlation between the enhancing effectiveness of the additive and the magnitude of apparent key kinetic parameters further supports that the reaction rate is primarily determined by mass transfer of isobutane.

To unravel the mass transfer-free kinetics behaviors, a mass transfer-free kinetic model for isobutane alkylation was successfully developed by decoupling N from the apparent kinetic model (Fig. 4f and Supplementary Note 9). Excellent agreement exists between the fitted results from the additive-free system and our previous experimental data39 (Fig. 4g), with confidence intervals for kinetic parameters an order of magnitude smaller than the rate constants. Specifically, the apparent kinetic parameters (k , k , k , k ) for this system are significantly lower, with the values of 1.03 kg mol-1 min-1, 4.36 kg mol-1 min-1, 108.49 kg mol-2 min-2, and 32.62 kg mol-2 min-2, respectively, than those derived from the mass transfer-free model, which yields constant values of 192.87 kg mol-1 min-1, 863.92 kg mol-1 min-1, 1688.16 kg mol-2 min-2, and 8457.40 kg mol-2 min-2, respectively, regardless of additive presence (Supplementary Table 7). The markedly higher values of mass transfer-free kinetics are consistent with the characteristics of instantaneous reaction, underscoring the need to decouple mass transfer effect.

The invariance of mass transfer-free kinetic parameters across varying PPG400 concentrations definitively confirms that the PPG400 enhancement on the isobutane alkylation process operates exclusively through modulating the N , without altering the reaction kinetics. This conclusion is robustly supported by the precise predictions of the mass transfer-free kinetics, which successfully predicted the time-dependent evolution of key product concentrations across systems with different PPG400 dosages, all showing strong agreement with experimental data (Fig. 4h, Supplementary Fig. 29).

To further elucidate the mass transfer-free nature of the alkylation reaction, Arrhenius parameters for key steps (k , k , k , and k ) were derived by plotting the logarithm of each rate constant ln(k) against 1/T, as shown in Figs. 4i-l and Supplementary Fig. 30, with the detailed activation energies and pre-exponential factors in Supplementary Table 8. The calculated activation energies for these elementary steps are consistently below 15.00 kJ/mol, a remarkably low value. These exceptionally low values are characteristic of ultrafast hydride transfer reactions, consistent with prior literature reporting values of 5–20 kJ/mol49. The term activation energies herein refer to the values derived from the chemical rate constants obtained after mathematically decoupling the mass transfer resistance. They are distinguished from the energies of individual elementary steps.

This theoretical insight explains the instantaneous reaction behavior and underscores why the process rate is predominantly governed by N rather than mass transfer-free chemical kinetics. The accurate predictive capability of the model, grounded in these mass transfer-free kinetic parameters, provides a powerful tool for optimizing the industrial alkylation process with additive.

Verification and comparison of additive enhancement performance

To further validate the rationality and reliability of the enhancement factor E, we systematically investigated the microscopic interfacial properties (𝛾, σ, D, ∆c *) and mesoscopic mass transfer parameters (d a, k , k a, N ) in systems with different ILs additives ([N ][C SO ], where m=4,8,14, and n=1,10,14, Fig. 5a) at a fixed ILs dosage of 0.3 wt%. MD simulation results (Supplementary Figs. 31-33 and Fig. 5b-c) confirmed that both cations and anions synergistically enhance interfacial properties. ILs additives with longer alkyl chains exhibited a more pronounced peak at the interface, leading to increased σ and ∆c *, and reduced D as well as 𝛾47,50. At the mesoscopic level, as the length of alkyl chains increases, a increases by reducing the d , while concurrently elevating steric hindrance at the interface. This heightened hindrance impedes the diffusion of isobutane, leading to a decrease in k (Fig. 5d). The net effect of these competing factors is a decrease in k a, as exemplified by the [N ][C SO ] system, where a 7.31% reduction in k outweighed a 6.48% gain in a, resulting in a drop in k a from 0.445 s-1 to 0.413 s-1 (Fig. 5e). However, N is determined not only by k a but also by the ∆c *, which serves as the fundamental driving force. The increase in N with longer alkyl chains is dominated by the significant rise in ∆c * resulting from IL-mediated optimization, rather than being limited by the reduction in k a.

Most importantly, the variation trends of parameter E across different ILs additive systems were in complete alignment with the experimentally measured RON (Fig. 5f), where the RON data were referenced from previous work37. The highest E, at 1.34, was observed in the [N ][C SO ] additive system, attributable to the greatest improvement in the N , demonstrating its superior mass transfer intensification effect. Furthermore, the parameter E, calculated from microscopic interfacial parameters obtained via MD simulations under a 1:1 I/O ratio, consistently matched the macroscopically observed enhancement in catalytic performance (Supplementary Fig. 34). This comprehensive validation strongly confirms the robustness of the parameter E as a predictive metric for interfacial enhancement.

To address concerns about generalizability, additional analyses were conducted to evaluate the E across 35 distinct ILs additive systems featuring diverse cationic structures and anionic species (Fig. 5g). This comparative analysis was conducted under a 1:1 I/O ratio model, which was selected for its more pronounced variation in the E value, thereby providing a more sensitive basis for comparison (Supplementary Figs. 35-37). Among all systems screened, [C C Phyr][C SO ] emerged as the most effective additive, yielding the highest E value of 5.87. The superiority of [C C Phyr][C SO ] can be attributed to its unique molecular structure, which is optimized to simultaneously maximize both k a and ∆c *, synergistically enhancing the N .

Furthermore, the model successfully identifies optimal additives based on multidimensional evaluation beyond a single parameter. A comparative analysis of key metrics demonstrated PPG400 has distinct advantages in terms of enhancement performance, cost-effectiveness, and low dosage requirement compared to other ILs (Fig. 5h). These practical benefits, combined with its environmentally benign advantages, specifically the absence of halogens and metallic elements, validate parameter E not only as a robust theoretical indictor but also as a practical tool for screening and identifying ideal additives like PPG400 for industrial alkylation.

Industrial alkylation process intensification

Actually, the alkylate production capacity in industry using pure H SO as catalyst with 98.3 wt% acid content is unreliable. Instead, the concentrated H SO in typical industrial reactors generally contains 6.0–7.0 wt% organics, 1.0–3.0 wt% water, and 90.0–92.0 wt% H SO , referred to as the used H SO to distinguish it from the fresh one40,51,52. The systematic alkylation experiments employing the used H SO as catalyst without and with the PPG400 additive were conducted, as described in Supplementary Figs. 38-40. Due to the positive effect induced by acid-soluble oil (ASO), the experimental results identified an optimal PPG400 dosage of 0.2 wt% in the used H SO -catalyzed system, which maximized the beneficial effects on alkylate quality with an elevated RON of 0.24 compared to the used H SO system. The detailed kinetic constants of the used H SO catalytic system without and with the addition of PPG400 additive were obtained, as listed in Supplementary Fig.41 and Table 9.

A detailed process simulation of the reaction effluent refrigeration process for C4 alkylation was conducted using the Aspen Plus simulation platform, with a custom user model based on complex reaction kinetics. The main unit equipment of the effluent refrigeration process is illustrated in Fig. 6a, and its specific process units are depicted in Supplementary Note 10 and Table 1018,53. Specifically, the influences of key operating parameters, including space time and feedstock I/O ratio, on the C4 alkylation process were systematically investigated for the system without and with the PPG400 additive. The quality and process capacity of alkylate were employed as the core indicators to assess the performance of the additive on the process intensification of C4 alkylation.

To achieve the optimal yield and quality of the alkylate, it is critical to maintain a sufficient space time (τ) of 20~30 minutes to ensure full emulsification between the acid and hydrocarbon phases40,43. The influences of space time on the alkylate composition, RON, and product yield were systematically investigated under a fixed reaction temperature, with comparisons between the system without and with the PPG400 additive, as illustrated in Fig. 6b. The alkylate composition under varied space times in both systems are further provided in Supplementary Fig. 42. The RON of the alkylate for the PPG400-aiding system with a space time of 20 min reaches 97.05, which is still higher than that of 96.71 in the used H SO system at 30 min. These results indicate that PPG400 effectively enhances both the RON and yield of the alkylate even under a shorter space time.

Two process intensification strategies were developed to utilize the advantages of PPG400 additive in enhancing the quality and process capacity of alkylate, with the core goal of increasing process capacity while ensuring the quality of alkylate is superior to the additive-free system. For the first strategy, increasing the feed quantity shortens the space time at a fixed reactor volume, thus leading to lower quality of alkylate (Fig. 6c and Supplementary Fig. 43). Notably, the PPG400-aiding system performed well even at a higher capacity of 100 kt/a within 20 min, achieving an alkylate RON of 96.90 and a C yield of 76.64%. This result is better than the RON of 96.52 and C yield of 75.42% obtained in the used H SO system at 80 kt/a with a space time of 25 min.

For the strategy of reducing the I/O ratio, the impacts of the I/O ratio on the composition of the alkylate, along with the capacity and RON in the used H SO -catalyzed alkylation process, both without and with the addition of the PPG400 additive, were explored (Fig. 6d). In the used H SO system, when the I/O ratio declines from 10:1 to 4:1, the RON gradually declines from 96.46 to 95.35, and the proportion of the low-RON components, including HEs, LEs, and DMHs, rises significantly (Supplementary Fig. 44). Despite the negative impact on product quality, reducing the I/O ratio substantially enhances process capacity. Specifically, when the I/O ratio is lowered from 10:1 to 4:1, the alkylate production capacity increases dramatically by 117.79%, from 84.90 kt/a to 184.90 kt/a. Excessively reducing the I/O ratio in pursuit of increased capacity will significantly exacerbate the load on the refrigeration and distillation sections. Against this backdrop, reducing the molar I/O ratio to 6:1 is a more suitable option for practical application. At an I/O ratio of 6:1 in the PPG400 system, the RON of the alkylate can be maintained at 96.66, with capacity reaching 133.67 kt/a, representing a 28.71% increase compared to the used H SO system without additive operating at the industrially standard I/O ratio of 8:1. These findings demonstrate that the addition of PPG400 additive can remarkably enhance product quality while simultaneously increasing production capacity, achieving by reducing the space time or feedstock I/O ratio.

Methods
MD simulation details

To simulate the behaviors of PPG400 additives at the H SO /C4 hydrocarbons interface, the OPLS-AA force field was employed to treat the interaction among the additives, H SO , and C4 hydrocarbons. The structures and force field parameters for the concentrated H SO (including the H SO molecule, bisulphate ion, and hydronium ion), as well as C4 hydrocarbons for MD simulations, were directly taken from our previous research22, 54. The force field parameters of PPG400 were obtained from LigParGen. The charges of the additives were optimized through the ChelpG method at the basis set of 6-311++G(d,p) level, utilizing the Gaussian 09 program.

In each simulation system, the C4 reactant box comprises 160 molecules of 2-butene and 2560 molecules of isobutane, with the box size of 8.0 × 8.0 × 4.0 nm3. The size of H SO box (8.0 × 8.0 × 24.0 nm3) contains 5696 H SO molecules, 168 hydronium ions, and 168 bisulphate ions55. For the interfacial simulation, a gap of 2 nm was maintained between the H SO box and the C4 hydrocarbons box to place PPG400 additives. The number of additives in the gap was 1, 4, 8, and 12, corresponding to the concentrations of 0.1, 0.3, 0.6, and 1.0 wt%, respectively. An initial energy minimization of 100000 steps was conducted to eliminate the unreasonable initial structure.

The canonical (NVT) simulations were performed at 281.15 K using nose-hoover thermostat for 10 ns. Subsequently, the isothermal-isobaric (NPT) ensemble was further carried out for 40.0 ns. To ensure full equilibration, the number density distribution of each component was sampled every 2.0 ns, and no apparent density deviations could be found. A further 30.0 ns NPT was performed for data collection with the time steps of 1.0 fs. To maintain a stable interface, the semi-isotropic Parrinello Rahman barostat method was applied along the z-axis, with a relaxation time of 2.0 ps at 1 bar for all NPT ensembles.

For all MD simulations, GROMACS software was employed with periodic boundary conditions (PBC) in three dimensions. Both Lennard-Jones interaction and Coulombic interaction were cut off at 1.2 nm. The LINCS algorithm was employed to manage all covalent bonds involving hydrogen atoms. Maxwell distribution was employed to obtain the initial atomic velocity. Long-range electrostatic interactions were addressed using the particle mesh Ewald method. It should be noted that the interface model constructed in this work can be considered as a pseudo phase model, which is used to quantify the interfacial composition, thermodynamic driving forces, and microscopic interfacial parameters (D, σ, 𝛾, ∆c *) of the additive-modified alkylation system. More detailed information for interfacial properties calculation was included in the Supplementary Notes 1-5.

CFD simulation details

To model the multiscale phenomena, 3D steady and transient CFD-PBM simulations were performed by ANSYS Workbench 2022 R2. The simplified structure of the stirring tank reactor was constructed by Space Claim 2022 R2. The Euler method for incompressible fluid is used to study the flow field in the liquid–liquid dispersion process. The reactor has three-blade flat impellers. The fluid domain was divided into a stationary domain and a rotational domain. The rotation of the impeller was simulated by multiple reference frames (MRF). The PBM was solved by the discrete method, which discretizes the droplet population into a finite number of size intervals.

Materials

All chemicals were purchased commercially and used as received. Fresh H SO (98 wt%) was bought from Sinopharm Chemical Reagent Co., Ltd. Polypropylene glycols (PPGs) were obtained from Shanghai Titan Scientific Co., Ltd. The Nitrogen (99.99%) gas was purchased from Air Liquide (Shanghai) Gas Co., Ltd. Mixed C4 hydrocarbons were obtained from Shanghai Weichuang Standard Gas Analysis Technology Co., Ltd. The detailed composition of Mixed C4 hydrocarbons is listed in Supplementary Table 2.

Experimental procedures

C4 alkylation was performed in a batch glass reactor at the temperature range of 273.15 to 285.15 K and an operating pressure of 0.5 MPa18. The dosages of PPG400 were 0.33, 0.66, 1.00, 2.00, and 3.30 g, corresponding to the mass percentages of 0.1, 0.2, 0.3, 0.6, and 1.0 wt%, respectively. A certain amount of PPG additives was dissolved in 180 ml of H SO and added to the reactor, followed by purging with N gas three times to remove air. Subsequently, 120 mL of a mixed C4 hydrocarbon feed, with a volume ratio of I/O 16:1, was introduced into the reactor while maintaining the pressure at 0.5 MPa to ensure the mixture remained in the liquid phase. The agitator was then adjusted to a stirring speed of 3000 rpm to achieve a uniform dispersion between the hydrocarbon phase and acid phase. Simultaneously, the temperature within the reactor was regulated using a thermostatic bath. After the given reaction time, the product mixtures were collected at the sampling outlet. The alkylate samples were then extracted and separated from the acid phase using carbon tetrachloride. The colorless transparent liquid in the upper layer was analyzed via gas chromatography (GC) to determine the octane number, with further analytical details provided in Supplementary Fig. 19.

Kinetic modeling

The fundamental understanding of reaction kinetics is crucial for gaining insights into reaction mechanisms and optimizing reactor design and processes. The alkylation reaction is complex, involving simultaneous reactions such as alkylation, polymerization, cracking, disproportionation, and self-alkylation, all mediated by carbonium ions56, 57. With over thirty iso-paraffins present, detecting each one using current analytical methods is challenging, particularly in a strong acid reaction system. Due to the close molecular weight, i.e., TMPs, DMHs, HEs, and LEs are treated to be one pseudo component, respectively. It is widely recognized that the C4 alkylation reaction occurs via the classical carbonium ion mechanism15. Building upon our prior work and informed by insights into the isomerization reactions of butene and the pathways for the formation of HEs, the alkylation kinetic model has been further refined39. Detailed kinetic modeling for information was included in the Supplementary Notes 7-9 and Tables 4-9.

Peer review rounds
[{"round": 1, "reviewer_comments": {"reviewer_1": "Dear Editor,\nI would like to express my sincere gratitude to the editor for providing me with the opportunity to review the manuscript titled\n\"Additive-mediated Interfacial Engineering of H2SO4-catalyzed Isobutane Alkylation: From Molecular Dynamics to Industrial\nProcess Intensification.\" In an era where research on electric vehicles and batteries is gaining significant attention, and the\nproduction of fossil fuels is facing considerable challenges, it is truly commendable that Sun and Zheng continue their\ninvestigation into sulfuric acid-catalyzed alkylation reactions. Realistically speaking, I hope their paper could be considered\nfor publication in Nature Communications to highlight the ongoing importance of catalytic processes in traditional energy\nsystems. However, there are several issues within the manuscript that warrant further discussion. I hope the authors will give\nthem careful consideration.\n1. We have carefully reviewed the manuscript and also read almost all of the papers published by Sun and Zheng's group\non isobutane alkylation. We observed that many of the methods and techniques used in this work have been repeatedly\nemployed in their previous papers. For instance, using molecular dynamics (MD) simulations to discuss interfacial layer\nthickness, diffusion coefficients, etc. It appears that the authors are applying the same methodology to discuss different\nadditive-sulfuric acid catalytic systems. While these methods are indeed effective and well-established, the frequent use of\nsimilar research approaches might significantly diminish the novelty of this work.\n2. The papers previously published by Sun and Zheng's group mention several additives, such as [OPSim][HSO4],\n[C8PSim][HSO4], [PSMim][HSO4], [OMim][HSO4], [OSMim][HSO4], [OPSim][HSO4]/H2SO4, quaternary ammonium ionic\nliquids... Why was PPG400 selected in this study? There are many cheap and effective surfactants available, so what\njustifies the choice of PPG400 as the additive? Additionally, why was only PPG400 chosen, and why were other molecular\nweights of PPG not considered?\n3.Upon reading the entire manuscript, it is clear that the isobutane-to-olefin ratio (I/O) is a key variable in this study.\nAccording to the paper, PPG400 makes isobutane-butene coordination the dominant component in the interfacial region,\nthereby reducing oligomerization of the olefins, etc. However, Corma et al. have emphasized in classical literature\n（Chemistry, Catalysts, and Processes for Isoparaffin–Olefin Alkylation: Actual Situation and Future Trends. Catal. Rev. Sci.\nEng. 35, 483–570 (1993)）that, in actual alkylation processes, due to the excess and re-circulation of isobutane, the I/O ratio\nat the acid-hydrocarbon interface can be as high as 1000:1. Even if the actual molar ratio of isobutane to butene at the\ninterface is not this high, it should not be lower than 1:1. The manuscript and supplementary materials repeatedly mention\nthat I/O is below 1 (with PPG400 increasing the I/O but still remaining below 1, Supplementary Table 2), which is\nunconvincing. More importantly, when performing MD simulations, why are the numbers of isobutane and butene molecules\nboth set to 440? In actual alkylation reaction experiments, the feed I/O is 16:1?\n4. Is the interfacial enhancement factor truly useful? The authors have performed a verification of this factor, but it is only\ntested with IL additives of different alkyl chain lengths ([N111m][CnSO4], m = 4, 8, 14, and n = 1, 10, 14). The authors have\nused various additives in sulfuric acid; is the E factor effective in all cases? We expect the E factor to be applicable to all (or\nat least most) additive-sulfuric acid systems for alkylation reactions. Furthermore, we hope the E factor could correlate the\nalkylation performance in other liquid acid systems (ionic liquids, HF, trifluoromethanesulfonic acid, Liquid coordination\ncomplexes, deep eutectic solvents). However, based on the current work, the E factor does not yet demonstrate broader\ngeneralizability.\n5. The article discusses the kinetics, and the solution of the ODE equation for the apparent kinetic model of the sulfuric acid\nsystem has always been a concern for researchers in reaction kinetics. Supplementary Note 12 | Apparent Kinetic Modeling\nbriefly outlines the method for determining the kinetic constants (ki). Unfortunately, the explanation is vague. Could the\nrelevant Matlab code be provided? How can readers trust that all calculated ki values fall within the 95% confidence\ninterval?\n6. There is a specific concern here. Equation 3 (line 289) discusses the mass transfer rate for Nisobutane. However, on the\nright-hand side, the explanation for C*isobutane states that \"Since isobutane is almost insoluble in the acid phase, the\nisobutane concentration in the acid phase can be considered as 0.\" This implies that Nisobutane would be equal to 0, which\nseems incorrect.\n7. Another point that may be unconvincing to readers is the statement: \"The process simulation with the inserted kinetic\nmodel predicts that PPG400 additive at 0.3 wt% can increase the alkylate capacity by 122.35%, from 83.53 kt/a to 185.73\nkt/a in the additive-free system.\" If this result were derived from a pilot or commercial-scale unit, it would indeed be\nremarkable. However, since it is based solely on a simulation in Aspen Plus, the conclusion lacks sufficient credibility.", "reviewer_2": "The manuscript addresses the impact of surface active substances on the performance of H2SO4 catalyzed alkylation. This\nis per se a very interesting topic and would be important for a variety of different processes. The currently chosen\nengineering aspects, however, must fall short to analyze the observed positive phenomena, because it does not link the\ncatalytic chemistry to the actual molecular transformation. The local concentrations will be important for entropic reasons, but\nit will require to consider the thermodynamic state of the constituents at the interface beyond the generation of a larger\ninterface between the sulfuric acid and hydrocarbon.\nBefore analyzing the shortfalls, I have two editorial remarks. One concerns the use of values beyond the comma, which are\nat large meaningless for the analysis and should be avoided whenever possible. The second is the use of composed figures\nwith tiles, which makes the analysis of the components more difficult for the reader. One should restrain the main text to\nthose figures which are relevant in the text and embed them to support the verbal description of the findings.\nSpecific comments:\n1. In order to analyze the impact of the local interface one would need to carefully remove the effect of the larger interfacial\narea induced by the surfactants. Without this information it is difficult to weigh and analyze the following deliberations.\n2. The major effect is attributed to changes in the local concentration of the hydrocarbons. I agree with this general\nassessment but would like to point out that the alkylation reaction is not limited by transport in a diffusion layer. The rate\ndetermining step is the hydride transfer from an isobutane molecule to the sulfate ester.\n3. The highlighted increase in octane number is related to the decrease in the dimethyl hexane formation. It did not change\nthe distribution between the trimethyl pentanes markedly, except for the slight decrease in the 223 TMP (the primary\nproduct), pointing to an even slightly reduced hydride transfer. In this respect it is important to also quantify the red oil\nformation, as one could speculate that the gain and conversion and octane number is related to a lower formation of red oil.\nThe speculation is supported by the impressive improvement of the alkylation products as displayed in figure 3c.\n4. The specificity of the surfactants, thus, appeared to change the local concentration of isobutane versus n-butene. It may be\ninteresting to understand the level of alkane in that mixture and the impact at the interface.\n5. It should be considered that the thermodynamic standard free energy of the constituents will change at that interface with\nchanging concentration, but the objective values of the free energies can be evaluated by the general composition, the gas\nphase pressure, and the local concentrations. Determining these concentrations at the interface and understanding the\nreaction between the isooctyl ester and isobutane will be crucial to rationalize the interesting observations.\nConcluding, let me state that this is a very interesting chemistry, but the current analysis does not allow to draw conclusions\nthat are transferable beyond the specific observations for the test case alkylation. I encourage the authors to conduct new\nexperiments and rethink the causes for the positive effect. At present, I do not recommend publication.", "reviewer_3": "Review comments: I would like to express my sincere gratitude to the editor for providing me with the opportunity to review the manuscript titled “Additive-mediated Interfacial Engineering of H2SO4-catalyzed Isobutane Alkylation: From Molecular Dynamics to Industrial Process Intensification.” In an era where research on electric vehicles and batteries is gaining significant attention, and the production of fossil fuels is facing considerable challenges, it is truly commendable that Sun and Zheng continue their investigation into sulfuric acid-catalyzed alkylation reactions. Realistically speaking, I hope their paper could be considered for publication in Nature Communications to highlight the ongoing importance of catalytic processes in traditional energy systems. However, there are several issues within the manuscript that warrant further discussion. I hope the authors will give them careful consideration.\n\nComment 1: We have carefully reviewed the manuscript and also read almost all of the papers published by Sun and Zheng's group on isobutane alkylation. We observed that many of the methods and techniques used in this work have been repeatedly employed in their previous papers. For instance, using molecular dynamics (MD) simulations to discuss interfacial layer thickness, diffusion coefficients, etc. It appears that the authors are applying the same methodology to discuss different additive-sulfuric acid catalytic systems. While these methods are indeed effective and well-established, the frequent use of similar research approaches might significantly diminish the novelty of this work.\n\nComment 2: The papers previously published by Sun and Zheng's group mention several additives, such as [OPSim][HSO4], [C PSim][HSO4], [PSMim][HSO4], [OMim][HSO4], [OSMim][HSO4], [OPSim][HSO4]/H2SO4, quaternary ammonium ionic liquids... Why was PPG400 selected in this study? There are many cheap and effective surfactants available, so what justifies the choice of PPG400 as the additive? Additionally, why was only PPG400 chosen, and why were other molecular weights of PPG not considered?\n\nComment 3. Upon reading the entire manuscript, it is clear that the isobutane-to-olefin ratio (I/O) is a key variable in this study. According to the paper, PPG400 makes isobutane-butene coordination the dominant component in the interfacial region, thereby reducing oligomerization of the olefins, etc. However, Corma et al. have emphasized in classical literature (Chemistry, Catalysts, and Processes for Isoparaffin-Olefin Alkylation: Actual Situation and Future Trends. Catal. Rev. Sci. Eng. 35, 483–570 (1993)) that, in actual alkylation processes, due to the excess and re-circulation of isobutane, the I/O ratio at the acid-hydrocarbon interface can be as high as 1000:1. Even if the actual molar ratio of isobutane to butene at the interface is not this high, it should not be lower than 1:1. The manuscript and supplementary materials repeatedly mention that I/O is below 1 (with PPG400 increasing the I/O but still remaining below 1, Supplementary Table 2), which is unconvincing. More importantly, when performing MD simulations, why are the numbers of isobutane and butene molecules both set to 440? In actual alkylation reaction experiments, the feed I/O is 16:1?\n\nComment 4. Is the interfacial enhancement factor truly useful? The authors have performed a verification of this factor, but it is only tested with IL additives of different alkyl chain lengths ([N111m][CnH2n+1SO4], m = 4, 8, 14, and n = 1, 10, 14). The authors have used various additives in sulfuric acid; is the E factor effective in all cases? We expect the E factor to be applicable to all (or at least most) additive-sulfuric acid systems for alkylation reactions. Furthermore, we hope the E factor could correlate the alkylation performance in other liquid acid systems (ionic liquids, HF, trifluoromethanesulfonic acid, Liquid coordination complexes, deep eutectic solvents). However, based on the current work, the E factor does not yet demonstrate broader generalizability.\n\nComment 5. The article discusses the kinetics, and the solution of the ODE equation for the apparent kinetic model of the sulfuric acid system has always been a concern for researchers in reaction kinetics. Supplementary Note 12 | Apparent Kinetic Modeling briefly outlines the method for determining the kinetic constants (ki). Unfortunately, the explanation is vague. Could the relevant Matlab code be provided? How can readers trust that all calculated ki values fall within the 95% confidence interval?\n\nComment 6. There is a specific concern here. Equation 3 (line 289) discusses the mass transfer rate for Nisobutane. However, on the right-hand side, the explanation for C*isobutane states that “Since isobutane is almost insoluble in the acid phase, the isobutane concentration in the acid phase can be considered as 0.” This implies that Nisobutane would be equal to 0, which seems incorrect.\n\nComment 7. Another point that may be unconvincing to readers is the statement: “The process simulation with the inserted kinetic model predicts that PPG400 additive at 0.3 wt% can increase the alkylate capacity by 122.35%, from 83.53 kt/a to 185.73 kt/a in the additive-free system.” If this result were derived from a pilot or commercial-scale unit, it would indeed be remarkable. However, since it is based solely on a simulation in Aspen Plus, the conclusion lacks sufficient credibility."}, "author_response": "General responses to all reviewers and the modifications for the\nrevised manuscript:\nWe sincerely appreciate all reviewers for the constructive comments that greatly\nhelp us to improve the quality of our manuscript. In the past few months, we have\nconducted a plenty of theoretical simulations and experimental studies to further\nelucidate the positive effect of the additive on enhancing the interfacial mass transfer\nflux of isobutane (N ) in H SO -catalyzed isobutane alkylation. Upon\nisobutane 2 4\nquantitatively coupling of the microscopic interfacial parameters and mesoscopic\ndroplet mass transfer model of the liquid/liquid dispersion system of H SO -catalyzed\n2 4\nisobutane alkylation, the droplet size distribution (d ), specific surface area (a), mass\np\ntransfer parameters (k , k a), and crucial mass transfer flux of isobutane (N ) were\nL L isobutane\ndetermined by complementary computational fluid dynamics (CFD)-population\nbalance model (PBM) simulation. Through the additional verification with 35 distinct\nILs additive systems, it has been proven that the interfacial enhancement factor E,\nestablished based on the ratio of N in the system with and without the additives,\nisobutane\ncan serve as an indicator for guiding the additives molecular design. Incorporating\nN into the apparent kinetic model, it is the first time to obtain the intrinsic\nisobutane\nactivation energy of the H SO -catalyzed isobutane alkylation via Arrhenius analysis\n2 4\nof the intrinsic rate constants, which quantitatively confirms it is a fast reaction\ndetermined by the mass transport of isobutane at the interface. Furthermore, the kinetic\nparameters were used to predict the industrial process intensification for the additive-\nmediated used H SO -catalyzed isobutane alkylation. With these new results, we have\n2 4\nthoroughly rewritten the manuscript, including the title, figures and most texts,\nresulting in almost a new paper. We summarize our major revisions on the manuscript\nfirst, then new results from theoretical simulations and additional experiments. Lastly,\nwe provide point-by-point responses to detailed comments from all referees.\n1. The major revisions on our manuscript are summarized as follows.\n1) The original title of “Additive-mediated interfacial engineering of H SO -catalyzed\n2 4\nisobutane alkylation: From molecular dynamics to industrial process intensification”\nwas revised as “Additive-mediated interfacial engineering of H SO -catalyzed\n2 4\nisobutane alkylation: From molecular design to industrial process intensification”. This\nvariation aims to emphasize the key point of “molecular design” and make the scientific\nimplications of this work clearer.\n2) The original manuscript presented a broad comparison of a series of novel additives\nat different dosages and temperatures, discussing their regulation of microscopic\ninterfacial properties, mesoscale mass transfer, and their impacts on macroscopic\nreaction performance and apparent kinetics. The analysis required deeper validation to\nfirmly establish the link between additive-induced interfacial modifications and the\nenhancement in mesoscale mass transfer, and to demonstrate the broader\ngeneralizability of the enhancement factor (E). In the revised manuscript, we have\nstrategically deepened our investigation by incorporating more variable conditions,\nincluding the reaction temperature and ratio of isobutane to olefins (I/O ratio), to\ncomprehensively illustrate the effect of additives on microscopic interfacial properties.\nThen, we have employed abundant MD and CFD-PBM simulations, kinetics analysis\nand process simulations to reveal the strengthening effect of additives from a multi-\nscale perspective. Furthermore, the study is expanded to include both non-ionic and\nionic additive systems, rigorously verifying the practicality and generalizability of the\nproposed theory.\n3) All the figures are revised, since many new results are supplemented. Fig. 1 in the\nrevised manuscript presents the MD simulation results along with error analysis, which\nelucidate the effect of PPG400 additive on the regulation of microscopic interfacial\ntransport at controlled interface coverage and varying temperature. Fig. 2 in the revised\nmanuscript includes the simulation results, along with error analysis, from the semi-\nempirical mesoscopic droplet mass transfer model and CFD-PBM model, respectively,\nto unravel the quantitative correlation between microscale interfacial characteristics\nand mesoscale mass transfer coefficients. Fig. 3 in the revised manuscript includes the\nestablishment of the interfacial enhancement factor E, and validates it by demonstrating\nits alignment with the alkylation reaction performance and kinetic analysis. Fig. 4 in\nthe revised manuscript validates the rationality and reliability of the enhancement factor\nE across the distinct ILs additive systems featuring diverse cationic structures and\nanionic species. Fig. 5 proposes the feasible strategies for industrial process\nintensification, developed through Aspen Plus simulations, which demonstrate a\npotential capacity increase of at least 24.85% while maintaining product quality through\nthe addition of PPG400. Except for the figures in the manuscript, we also supplemented\nmany related results in the revised supplementary materials.\n2. New results from theoretical simulations are further summarized.\n1) More MD simulations for determining microscale interfacial properties\nTo get an insight into the effect of PPG400 additive on the regulation of\nmicroscopic interfacial transport, the detailed interfacial properties for the H SO -\n2 4\ncatalyzed isobutane alkylation system without and with PPG400 additive at different\ninterface coverages and temperature were reinvestigated via MD simulations under the\n16:1 isobutane/olefin (I/O) feed ratio, ensuring full consistency between our MD\ncomputational models and experimental conditions (Fig. R1). Furthermore, four\nrepresentative microscopic interfacial parameters, including interfacial tension (𝛾),\ninterfacial thickness (σ), diffusion coefficients (D), and interfacial concentration\ndifference of isobutane between the interface and the acid phase (∆c *) were\nisobutane\ndetermined, underscoring the role of additives in regulating interfacial properties.\n[...]"}, {"round": 2, "reviewer_comments": {"reviewer_2": "The authors have answered all my questions.", "reviewer_4": "[Note from the Editor: Reviewer #4 was asked to assess the response given to reviewer #1.]\nAfter carefully reviewing the authors' responses to all of reviewer 1's observations, I can conclude that the authors have\nthorougly addressed all of this reviewer's observations and comments, and from my point of view, I consider that, as far as\nreviewer 1 is concerned, the manuscript is ready for publication. The work supports the conclusions and is novel, interesting,\nand well-structured.\nThe authors have demonstrated that, despite employing a widely used theoretical tool for the alkylation reaction, their work\ndelves into several aspects of the process, contributing to the novelty of their research.\nMy only regret is that the highest-performing formulation continues to contain H₂SO₄, which remains a highly toxic and\ncorrosive product that requires significant water for its removal. Therefore, it should be completely eliminated in favor of\nenvironmentally friendly catalysts such as the ionic liquids proposed in this work.", "reviewer_5": "[Note from the Editor: Reviewer #5 was asked to assess the response given to reviewer #3.]\nThe rebuttal provided by Ma et al. represents a comprehensive and technically rigorous response to the multi-scale\nconcerns raised by the reviewers. By integrating Molecular Dynamics (MD), Computational Fluid Dynamics (CFD), and\nexperimental validation, the authors have significantly strengthened the manuscript. However, to fully satisfy the specific\ninquiries of Reviewer 3 regarding the interfacial species' status and the validity of the calculated kinetic parameters,\nfurther clarification is required.\nInterfacial Thermodynamic State and Species Status: Reviewer 3 repeatedly emphasizes the need to characterize the\nthermodynamic state of the constituents at the interface. While the authors respond with Potential of Mean Force (PMF)\ncalculations to demonstrate changes in the energy barrier (ΔPMF) for isobutane, the response remains somewhat focused\non the macroscopic result (mass transfer flux) rather than the microscopic nature of the species itself.\nThe reviewer is seeking an understanding of how the surfactant environment alters the chemical potential and local\nenvironment of the intermediate species (e.g., carbonium ions or sulfate esters) at the liquid-liquid interface. The current\nrebuttal provides a \"black box\" approach where the interface is a region of modified resistance, but it does not fully elucidate\nthe solvation state or orientation of the reactants within the PPG400 layer. To bridge this gap, the authors should explicitly\nstate that their model treats the interface as a pseudo-phase where measurable bulk parameters are modified by local\nenrichment factors. While this engineering approach is practical for industrial process intensification, it acknowledges the\n\"thermodynamic state\" primarily through the lens of concentration gradients and energy barriers rather than molecular\nspectroscopy or transition state theory.\nKinetic Modeling and Activation Energies: A significant point of contention involves the calculation of activation energies.\nThe authors claim to have decoupled the intrinsic kinetics from mass transfer to obtain \"intrinsic\" activation energies below\n15 kJ/mol. However, as noted, these values may still be apparent rather than representative of a single elementary step. In a\ncomplex liquid-liquid system, the measured rate constant is a convolution of: Intrinsic Chemical Kinetics: The actual Ea;\nDiffusion/Mass Transfer: Regulated by the interfacial enhancement factor; Mixing Effects: As demonstrated by the sensitivity\nto stirring rates.\nThe current method of plotting ln(k) vs 1/T after \"decoupling\" Nisobutane assumes that all non-chemical barriers have been\nperfectly accounted for. If the mass transfer model (CFD-PBM) has even a small margin of error, that error is propagated\ninto the \"intrinsic\" k and subsequently the Ea. To improve the clarity of the rebuttal, the authors should adopt a more integrated\nmodeling approach. Instead of a sequential fit, the model should simultaneously solve the Ordinary Differential Equations\n(ODEs) for kinetics, diffusion, and mixing, using temperature (T) as a global parameter. This would allow the entire kinetic\nmanifold to be fitted across different temperatures, ensuring that the temperature dependence of physical properties\n(viscosity, D) is not mistaken for chemical activation energy.\nOverall Assessment: Despite these nuances, the work is very solid. The authors have gone to great lengths to provide\nindustrial validation with pilot plant data from 2019 to bridge the gap between Aspen simulations and reality; multi-scale\nconsistency, showing that the trends in 1:1 and 16:1 I/O ratios are consistent, which justifies the use of MD for microscale\ninsights; economic viability, a clear cost-benefit analysis that justifies PPG400 as a practical industrial additive. If the authors\ncan be more transparent about the limitations of their \"intrinsic\" parameters and the specific thermodynamic environment of\nthe interfacial species, the manuscript will be well-positioned for publication in a high-impact journal such as Nature\nCommunications."}, "author_response": "Point-by-point reply to Reviewers’ comments\nManuscript ID: NCOMMS-25-19174\nTitle: Additive-mediated Interfacial Engineering of H SO -catalyzed Isobutane\n2 4\nAlkylation: From Molecular Design to Industrial Process Intensification\nAuthors: Zhihong Ma1, Yijie Ding1, Weizhen Sun*,1, Ling Zhao1, Wenli Du2, and\nWeizhong Zheng*,1\n[...]"}]

Decision letter