Experimental screening of Metal Organic Frameworks (MOFs) for separation applications can be costly and time-consuming. Computational methods can provide many benefits in this process, as expensive compounds and a wide range of operating conditions can be tested while crucial mechanistic insights are gained. TAMOF-1, a recently developed MOF, stands out for its exceptional stability, robustness and cost-effective synthesis. Its good CO2 uptake capacity makes it a promising agent for flue gas separation applications. In this work, we combine experiments with simulations at the atomistic and numerical level to investigate the adsorption and separation of CO2 and N2. Using Monte Carlo simulations, we accurately reproduce experimental adsorption isotherms and elucidate the adsorption mechanisms. TAMOF-1 effectively separates CO2 from N2 because of preferential binding sites near Cu2+ atoms. To assess separation performance in equilibrium at different conditions along the entire isotherm pressure range, adsorbed mole fractions, selectivities, and the trade-off between selectivity and uptake (TSN) are calculated. The dynamic separation performance is assessed by breakthrough experiments and numerical simulations, demonstrating efficient dynamic separation of CO2 and N2, with CO2 being retained in the column.

Cyclopentyl methyl ether (CPME) is a promising green solvent due to its eco-friendly properties; it is produced by adding methanol (MeOH) to cyclopentene. Separation of the resulting product mixture containing CPME and MeOH is critical, and it requires vapor-liquid equilibrium (VLE) data. In this work, isobaric VLE data were measured experimentally using an ebulliometer in a 60.0–101.3 kPa pressure range for a binary system of CPME + MeOH. VLE data were modeled using excess Gibbs (G (Formula presented.)) energy-based models such as Wilson, NRTL, and UNIQUAC. The formation of an azeotrope was analyzed. Flash point, surface tension, Gibbs adsorption, and thickness of surface layer were estimated using the Wilson model, which can help in determining molecule interaction and overall behavior of the system. Atmospheric and high-pressure distillation columns were designed using Aspen Plus to study the separation of CPME + MeOH, and an economic evaluation of the same was carried out.

Computation of the excess entropy (Formula presented.) from the second-order density expansion of the entropy holds strictly for infinite systems in the limit of small densities. For the reliable and efficient computation of (Formula presented.) it is important to understand finite-size effects. Here, expressions to compute (Formula presented.) and Kirkwood–Buff (KB) integrals by integrating the Radial Distribution Function (RDF) in a finite volume are derived, from which (Formula presented.) and KB integrals in the thermodynamic limit are obtained. The scaling of these integrals with system size is studied. We show that the integrals of (Formula presented.) converge faster than KB integrals. We compute (Formula presented.) from Monte Carlo simulations using the Wang–Ramírez–Dobnikar–Frenkel pair interaction potential by thermodynamic integration and by integration of the RDF. We show that (Formula presented.) computed by integrating the RDF is identical to that of (Formula presented.) computed from thermodynamic integration at low densities, provided the RDF is extrapolated to the thermodynamic limit. At higher densities, differences up to (Formula presented.) are observed.

Heat pumps, which recycle waste heat, are a promising technology for reducing CO₂ emissions. Efficiently using low-grade waste heat remains challenging due to the limitations of standard heat exchangers and the need for more effective working fluids. This work introduces a multi-scale methodology that combines force field-based Monte Carlo simulations, quantum mechanics, and equations of state to explore the potential of formic acid as a new reactive fluid in thermodynamic cycles. Formic acid exhibits dimerization behavior, forming cyclic dimers in the gas phase, which can enhance the thermodynamic efficiency of heat recovery systems. The dimerization reaction of formic acid is crucial because it integrates chemical energy into thermodynamic processes, potentially improving the performance of heat pumps and other energy systems. The study implements umbrella sampling in Monte Carlo simulations to compute the thermodynamic properties of HCOOH dimerization, including equilibrium constants, enthalpy, and entropy. Results from two different methods to study dimer formation, namely the dimer counter method and the potential of mean force method, show strong agreement with the enthalpy of dimerization of −60.46 kJ mol⁻¹ and −62.91 kJ mol⁻¹, and entropy of −137.36 J mol⁻¹K⁻¹ and −146.98 J mol⁻¹K⁻¹, respectively. A very good agreement of the Monte Carlo results with Quantum Mechanics and experimental data validates the accuracy of the simulations. For phase equilibrium properties, the Peng–Robinson equation of state, coupled with advanced mixing rules, was applied and compared to Monte Carlo simulations in the Gibbs ensemble. This approach enabled the determination of the Global Phase Equilibrium of the system, vaporization enthalpy, phase composition, vapor and liquid densities of the coexisting phases, and entropy as a function of temperature. The agreement between the thermodynamic model and Monte Carlo simulations confirms the reliability of the methodology in capturing the phase behavior of the system. The findings demonstrate a promising approach for discovering and characterizing new reactive fluids, contributing to more efficient and sustainable energy technologies.

Hydrate-based H2 storage is based on the mechanism of trapping H2 in water-based structures that are environmentally friendly and cost-efficient. Understanding the effects of common promoters on hydrate-based H2 storage at the molecular level is crucial for designing efficient storage systems, and for discovering novel promoters. Here, a series of μs-scale molecular dynamics simulations are performed to investigate the nucleation of binary H2 hydrates from gas-liquid two-phase solutions in the presence of various promoters, i.e., CH4, CO2, C2H6, C3H8, C5H10, and THF. The simulation results indicate that the H2 and promoter molecules first dissolve in water from the gas phase and then are absorbed on the cage-faces, promoting the nucleation and growth of binary H2 hydrates. THF is the most effective promoter for hydrate-based H2 storage, exhibiting high performance in converting H2 from the gas phase to hydrates. It is followed by CH4, C2H6, and CO2; C3H8 and C5H10 molecules are less effective H2 hydrate promoters. The presence of large promoter molecules enhances multi-occupied cage formation. The molecular insight into the nucleation of binary H2 hydrates with various promoters provided here not only contributes to a broader understanding of hydrate-based H2 storage but is expected to motivate further experimental and computational studies.

One of the most promising energy carriers for transport applications are hydrogen-based energy carriers. NaBH₄ is a hydrogen energy carrier and produces hydrogen bubbles when it is dissolved in water. The formation of hydrogen bubbles hinders experimental measurements of the thermodynamic and transport properties of aqueous NaBH₄ solutions at elevated temperatures. Accurate knowledge of these properties is essential for the NaBH₄ hydrolysis reactor modeling and design. Molecular dynamics (MD) simulations provide the option to study the thermodynamic and transport properties of NaBH₄ aqueous solutions without hindering hydrogen bubble formation. In this work, a new force field is developed for BH₄^-, namely, the Delft force field of BH₄^- (DFF/BH₄^-), which, combined with additional force fields, can accurately describe experimental densities and viscosities of 0 to 5 m (mol salt/kg water) NaBH₄, 0 to 3 m NaB(OH)₄, and 1 m NaOH aqueous solutions at 295 K within 1.8% and 10.8% maximum deviation, respectively. Empirical fitting correlations are created for densities, viscosities, and self-diffusivities obtained from the MD simulations of 0 to 5 m NaBH₄, 0 to 5 m NaB(OH)₄, and 0 to 1 m NaOH aqueous solutions at 295-363 K for NaBH₄ hydrolysis reactor modeling and design purposes.

We study important aspects of shape selectivity effects of zeolites for hydroisomerization of linear alkanes, which produces a myriad of isomers, particularly for long chain hydrocarbons. To investigate the conditions for achieving an optimal yield of branched hydrocarbons, it is important to understand the role of chemical equilibrium in these reversible reactions. We conduct an extensive analysis of shape selectivity effects of different zeolites for the hydroisomerization of C₇ and C₈ isomers at chemical reaction equilibrium conditions. The reaction ensemble Monte Carlo method, coupled with grand-canonical Monte Carlo simulations, is commonly used for computing reaction equilibrium of heterogeneous reactions. The computational demands become prohibitive for a large number of reactions. We used a faster alternative in which reaction equilibrium is obtained by imposing chemical equilibrium in the gas phase and phase equilibrium between the gas phase components and the adsorbed phase counterparts. This effectively mimics the chemical equilibrium distribution in the adsorbed phase. Using Henry’s law at infinite dilution and mixture adsorption isotherm models at elevated pressures, we calculate the adsorbed loadings in the zeolites. This study shows that zeolites with cage or channel-like structures exhibit significant differences in selectivity for alkane isomers. We also observe a minimal impact of pressure on the gas-phase equilibrium of these reactions at typical experimental reaction temperatures 400 − 700 K . This study marks initial strides in understanding the reaction product distribution for long-chain alkanes.

Linear regression (LR) is used to predict thermochemical properties of alkanes at temperatures (0–1000) K to study chemical reaction equilibria inside zeolites. The thermochemical properties of C1 until C10 isomers reported by Scott are used as training data sets in the LR model which is used to predict these properties for alkanes longer than C10 isomers. Second-order groups are used as independent variables which account for the interactions between the neighboring groups of atoms. This model accurately predicts Gibbs free energies, enthalpies, Gibbs free energies of formation, and enthalpies of formation for alkanes which exceeds the chemical accuracy of 1 kcal/mol and outperforms the group contribution methods developed by Benson et al., Joback and Reid, and Constantinou and Gani. Predictions from our model are used to compute the reaction equilibrium distribution of hydroisomerization of C10 and C14 isomers in MTW-type zeolite. Calculation of reaction equilibrium distribution inside zeolites also requires Henry coefficients of the isomers which can be computed using classical force field-based molecular simulations using the RASPA2 software for which we created an automated workflow. The reaction equilibrium distribution for C10 isomers obtained using the LR model and the training data set for this model are in very good agreement. The tools developed in this study will enable the computational study of hydroisomerization of long-chain alkanes (>C10).

Molecular-based equations of state for describing the thermodynamics of chain molecules are often based on mean-field like arguments that reduce the problem of describing the interactions between chains to a simpler one involving only nonbonded monomers. While for dense liquids such arguments are known to work well, at low density they are typically less appropriate due to an incomplete description of the effect of chain connectivity on the local environment of the chains’ monomer segments. To address this issue, we develop three semi-empirical approaches that significantly improve the thermodynamic description of chain molecules at low density. The approaches are developed for chain molecules with repulsive intermolecular forces; therefore, they could be used as reference models for developing equations of the state of real fluids based on perturbation theory. All three approaches are extensions of Wertheim’s first-order thermodynamic perturbation theory (TPT1) for polymerization. The first model, referred to as TPT1-v, incorporates a second-virial correction that is scaled to zero at liquid-like densities. The second model, referred to as TPT1-y, introduces a Helmholtz-energy contribution to account for correlations between next-nearest-neighbor segments within chain molecules. The third approach, called TPT-E, directly modifies TPT1 without utilizing an additional Helmholtz energy contribution. By employing TPT1 at the core of these approaches, we ensure an accurate description of mixtures and enable a seamless extension from chains of tangentially bonded hard-sphere segments of equal size to hetero-segmented chains, fused chains, and chains of soft repulsive segments (which are influenced by temperature). The low-density corrections implemented in TPT1 are designed to preserve these good characteristics, as confirmed through comparisons with novel molecular simulation results for the pressure of various chain fluids. TPT1-v exhibits excellent transferability across different chain types, but it relies on knowing the second virial coefficient of the chain molecules, which is non-trivial to obtain and determined here using Monte Carlo simulation. The TPT1-y model, on the other hand, achieves comparable accuracy to TPT1-v while being fully predictive, requiring no input besides the geometry of the chain molecules.

We explore the impact of force field parameters and reaction equilibrium on the scaling behavior towards the critical point in reactive binary systems, focusing on NO ₂/N ₂O ₄. This system can be considered as a special single-component system since NO ₂ and N ₂O ₄ are in chemical equilibrium via the chemical reaction 2NO ₂⇌N ₂O ₄. We simplify the system by representing both components as single LJ particles, achieving excellent agreement with densities computed using molecular simulations in which all-atom force fields were used. We investigate the effect of force field parameters (ɛ and σ) on phase behavior and show that the critical exponent β remains constant, which means that intermolecular interactions do not affect the scaling to the critical point when the chemical reaction takes place. We also investigate the sensitivity of the reaction equilibrium constant and show that even small changes in isolated molecule partition functions lead to large differences in chemical equilibria. We show that the critical exponent β is different for systems with different reaction equilibrium constants, so a careful parameterization of β is needed for an accurate computation of critical temperatures of reactive mixtures. We perform a screening of reactive binary mixtures for a wide range of ideal gas reaction equilibrium constants, revealing key insights into the thermodynamic behavior and critical properties. Thereby we facilitate the efficient screening of reactive binary mixtures for various applications. Our results emphasize the importance of accurately parameterizing β and provide valuable insights into the critical scaling behavior of complex reactive systems.

Continuous Fractional Component Monte Carlo (CFCMC) and molecular dynamics (MD) simulations are performed to calculate the solubilities and self-diffusion coefficients of four light n-alkanes (methane, ethane, propane, and n-butane) in aqueous NaCl solutions as well as the thermodynamic properties of their corresponding hydrate crystals. Correction factors k_ij to the Lorentz-Berthelot combining rules for alkane groups (CH₃) and water are optimized (k_ij = 1.04) by fitting excess chemical potentials to experimental data at 1 bar and 298.15 K. Using these values of k_ij, we calculate the solubilities of the four alkanes in aqueous NaCl solutions with different molalities (0-6) mol/kg at different temperatures (278.15-308.15) K and pressures (1, 100, 200, 300) bar. The diffusion coefficients of the four alkanes in NaCl solutions (0-6) mol/kg are calculated at different temperatures (278.15-308.15) K and 1 bar and corrected for the finite-size effects. The lattice parameters of the corresponding hydrates with different guest molecules are computed using MD simulations at different temperatures (150-290) K and pressures (5-700) MPa. Isothermal compressibilities at 287.15 K and thermal expansion coefficients at 14.5 MPa for the corresponding hydrates are calculated. We present an extensive collection of thermodynamic data related to gas hydrates that contribute to a fundamental understanding of natural gas hydrate science.

Vapor-Liquid Equilibria (VLE) of hydrogen (H₂) and aqueous electrolyte (KOH and NaCl) solutions are central to numerous industrial applications such as alkaline electrolysis and underground hydrogen storage. Continuous fractional component Monte Carlo simulations are performed to compute the VLE of H₂ and aqueous electrolyte solutions at 298-423 K, 10-400 bar, 0-8 mol KOH/kg water, and 0-6 mol NaCl/kg water. The densities and activities of water in aqueous KOH and NaCl solutions are accurately modeled (within 2% deviation from experiments) using the non-polarizable Madrid-2019 Na⁺/Cl⁻ ion force fields for NaCl and the Madrid-Transport K⁺ and Delft Force Field of OH⁻ for KOH, combined with the TIP4P/2005 water force field. A free energy correction (independent of pressure, salt type, and salt molality) is applied to the computed infinite dilution excess chemical potentials of H₂ and water, resulting in accurate predictions (within 5% of experiments) for the solubilities of H₂ in water and the saturated vapor pressures of water for a temperature range of 298-363 K. The compositions of water and H₂ are computed using an iterative scheme from the liquid phase excess chemical potentials and densities, in which the gas phase fugacities are computed using the GERG-2008 equation of state. For the first time, the VLE of H₂ and aqueous KOH/NaCl systems are accurately captured with respect to experiments (i.e., for both the liquid and gas phase compositions) without compromising the liquid phase properties or performing any refitting of force fields.

Non-polarizable force fields fail to accurately predict free energies of aqueous electrolytes without compromising the predictive ability for densities and transport properties. A new approach is presented in which (1) TIP4P/2005 water and scaled charge force fields are used to describe the interactions in the liquid phase and (2) an additional Effective Charge Surface (ECS) is used to compute free energies at zero additional computational expense. The ECS is obtained using a single temperature-independent charge scaling parameter per species. Thereby, the chemical potential of water and the free energies of hydration of various aqueous salts (e.g., NaCl and LiCl) are accurately described (deviations less than 5% from experiments), in sharp contrast to calculations where the ECS is omitted (deviations larger than 20%). This approach enables accurate predictions of free energies of aqueous electrolyte solutions using non-polarizable force fields, without compromising liquid-phase properties.

The confinement effect of porous materials on the thermodynamical equilibrium of the CO₂ hydrogenation reaction presents a cost-effective alternative to transition metal catalysts. In metal-organic frameworks, the type of metal center has a greater impact on the enhancement of formic acid production than the scale of confinement resulting from the pore size. The M-MOF-74 series enables a comprehensive study of how different metal centers affect HCOOH production, minimizing the effect of pore size. In this work, molecular simulations were used to analyze the adsorption of HCOOH and the CO₂ hydrogenation reaction in M-MOF-74, where M = Ni, Cu, Co, Fe, Mn, Zn. We combine classical simulations and density functional theory calculations to gain insights into the mechanisms that govern the low coverage adsorption of HCOOH in the surrounding of the metal centers of M-MOF-74. The impact of metal centers on the HCOOH yield was assessed by Monte Carlo simulations in the grand-canonical ensemble, using gas-phase compositions of CO₂, H₂, and HCOOH at chemical equilibrium at 298.15-800 K, 1-60 bar. The performance of M-MOF-74 in HCOOH production follows the same order as the uptake and the heat of HCOOH adsorption: Ni > Co > Fe > Mn > Zn > Cu. Ni-MOF-74 increases the mole fraction of HCOOH by ca. 10⁵ times compared to the gas phase at 298.15 K, 60 bar. Ni-MOF-74 has the potential to be more economically attractive for CO₂ conversion than transition metal catalysts, achieving HCOOH production at concentrations comparable to the highest formate levels reported for transition metal catalysts and offering a more valuable molecular form of the product.

The series of metal–organic frameworks M-MOF-74 gained popularity in the field of capture and separation of CO₂ due to the presence of numerous, highly reactive open-metal sites. The description of effective interactions between guest molecules and open-metal sites without accounting for polarization effects is challenging but it can significantly reduce the computational cost of simulations. In this study, we propose a non-polarizable force field for CO₂, and H₂ adsorption in M-MOF-74 (M = Ni, Cu, Co, Fe, Mn, Zn) by scaling the Coulombic interactions of M-MOF-74 atoms, and Lennard-Jones interaction potentials between the center of mass of H₂ and the open-metal centers. The presented force field is based on UFF and DREIDING parameters, characterized by high transferability and efficiency. The quantum behavior of H₂ at cryogenic temperatures is considered by incorporating Feynman–Hibbs quantum corrections. To validate the force field, the experimental isotherms of CO₂ at 298 K and 10⁻¹ – 10²kPa, the isotherms of H₂ at 77 K and 10⁻⁵ – 10²kPa, the corresponding enthalpy of adsorption, and the binding geometries in the M-MOF-74 series were reproduced using Monte Carlo simulations in the grand-canonical ensemble. The computed loadings, heats of CO₂ and H₂ adsorption, and binding geometries in M-MOF-74 are in very good agreement with the experimental values. The temperature transferability of the force field from 77 K to 87 K, and 298 K was shown for adsorption of H₂. The validated force field was used to study the adsorption and separation of CO₂/H₂ mixtures at 298 K. The adsorption of H₂ practically does not occur when CO₂ is present in the mixture. As indicated from simulated breakthrough curves, the breakthrough time of CO₂ in M-MOF-74 follows the same order as the uptake and the heat of CO₂ adsorption: Ni ¿ Co ¿ Fe ¿ Mn ¿ Zn ¿ Cu. Increasing the feed mole fraction of CO₂ in the breakthrough simulations from 0.1 to 0.9 speeds up the saturation of the adsorbent, leading to a faster exit of CO₂ with the column effluent. The application of the non-polarizable force field allows full investigation of the capture and separation of CO₂ in M-MOF-74, and can be expanded to study multi-component mixtures or industrial reactions in future research.

Knowledge of the microscopic behavior of CO₂ hydrates in oceanic sediments is crucial to evaluate the efficiency and stability of hydrate-based CO₂ sequestration in oceans. Here, systematic molecular dynamics simulations are executed to investigate the growth and dissociation of CO₂ hydrates, and the mechanical instability of CO₂ hydrate-Illite interface in the brine-urea-Illite system. Simulation results show that the CO₂ hydrate growth is jointly affected by the confined space, Illite surface properties, and presence of urea. Specifically, the interfacial H₂O and the ion layer on the Illite surface hinder the growth of CO₂ hydrate crystals toward Illite surfaces. Urea molecules can bind salt ions and increase CO₂ concentrations in the water, thus kinetically promoting CO₂ hydrate growth. The dissociation of the CO₂ hydrate is affected by Illite surface properties and the CO₂ hydrate structure. CO₂ hydrate starts from the regions where hydrate particles are minimally in contact and extends on both sides. The mechanical tension and compression of the CO₂ hydrate-Illite interface exhibit nonlinear characteristics by changing the hydrogen bonds and the CO₂ hydrate structure. The molecular insight into the microscopic behavior of CO₂ hydrates in the brine-urea-Illite system contributes to a broader understanding of hydrate-based CO₂ sequestration.

Entropies for alkane isomers longer than C10 are computed using our recently developed linear regression model for thermochemical properties which is based on second-order group contributions. The computed entropies show excellent agreement with experimental data and data from Scott’s tables which are obtained from a statistical mechanics-based correlation. Entropy production and heat input are calculated for the hydroisomerization of C7 isomers in various zeolites (FAU-, ITQ-29-, BEA-, MEL-, MFI-, MTW-, and MRE-types) at 500 K at chemical equilibrium. Small variations in these properties are observed because of the differences in reaction equilibrium distributions for these zeolites. The effect of chain length on heat input and entropy production is also studied for the hydroisomerization of C7, C8, C10, and C14 isomers in MTW-type zeolite at 500 K. For longer chains, both heat input and entropy production increase. Enthalpies and absolute entropies of C7 hydroisomerization reaction products in MTW-type zeolite increase with higher temperatures. These findings highlight the accuracy of our linear regression model in computing entropies for alkanes and provide insight for designing and optimizing zeolite-catalyzed hydroisomerization processes.

Knowledge on the kinetics of gas hydrate dissociation in clay pores at static and dynamic fluid conditions is a fundamental scientific issue for improving gas production efficiency from hydrate deposits using thermal stimulation and depressurization respectively. Here, molecular dynamics simulations were used to investigate poly- and mono-crystalline methane hydrates in Na-montmorillonite clay nanopores. Simulation results show that hydrate dissociation is highly sensitive to temperature and pressure gradients, but their effects differ. Temperature changes increase thermal instability of water and gas molecules, leading to layer-by-layer dissociation from the outer surface. Under flow conditions, laminar flow predominates in nano-pores, and non-Darcy flow occurs due to clay-fluid interactions. Viscous flow disrupts hydrogen bonding at the hydrate surface, enhancing kinetic instability of water. Grain boundaries of polycrystalline hydrates are less stable compared to bulk phases and preferentially decompose, forming new dissociation fronts. This accelerates dissociation compared to monocrystalline hydrates. Fracture occurs at the grain boundaries of polycrystalline hydrate in the fluid, resulting in separate hydrate crystal grains. This fracture process further accelerates hydrate dissociation. In flow systems, methane nanobubbles form in fluid and readily transport with fluid flow. Unlike surface nanobubbles at static conditions, these liquid nanobubbles exhibit mobility. The findings of this study can contribute to a better understanding of the complex phase transition behavior of hydrate in confined environment, and provide theoretical support for improving production control technology.

Focused ultrasound has experimentally been found to enhance the diffusion of nanoparticles; our aim with this work is to study this effect closer using both experiments and non-equilibrium molecular dynamics. Measurements from single particle tracking of 40 nm polystyrene nanoparticles in an agarose hydrogel with and without focused ultrasound are presented and compared with a previous experimental study using 100 nm polystyrene nanoparticles. In both cases, we observed an increase in the mean square displacement during focused ultrasound treatment. We developed a coarse-grained non-equilibrium molecular dynamics model with an implicit solvent to investigate the increase in the mean square displacement and its frequency and amplitude dependencies. This model consists of polymer fibers and two sizes of nanoparticles, and the effect of the focused ultrasound was modeled as an external oscillating force field. A comparison between the simulation and experimental results shows similar mean square displacement trends, suggesting that the particle velocity is a significant contributor to the observed ultrasound-enhanced mean square displacement. The resulting diffusion coefficients from the model are compared to the diffusion equation for a two-time continuous time random walk. The model is found to have the same frequency dependency. At lower particle velocity amplitude values, the model has a quadratic relation with the particle velocity amplitude as described by the two-time continuous time random walk derived diffusion equation, but at higher amplitudes, the model deviates, and its diffusion coefficient reaches the non-hindered diffusion coefficient. This observation suggests that at higher ultrasound intensities in hydrogels, the non-hindered diffusion coefficient can be used.

The use of reactive working fluids in thermodynamic cycles is currently being considered as an alternative to inert working fluids, because of the preliminarily attested higher energy-efficiency potential. The current needs to simulate their use in thermodynamic cycles, which may operate in liquid, vapour or vapour-liquid state, are an accurate real-fluid equation of state and ideal gas thermochemical properties of each molecule constituting the mixture, to calculate the equilibrium constant. To this end, the appeal to a multi-scale theoretical methodology is paramount and its definition represents the objective of the present work. This methodology is applied and validated on the system N₂O₄ ⇌ 2NO₂. Firstly, the equations solved for simultaneous two-phase and reaction equilibrium are presented. Secondly, ideal gas thermochemical properties of N₂O₄ and NO₂ are computed at atomic scale by quantum mechanics simulations. Then, to apply the selected cubic equation of state, pure-component properties of the species forming the reactive mixture (critical point coordinates and acentric factor) are required as input. However, these properties are not measurable, since NO₂ and N₂O₄ do not exist in nature as pure components. To get around this difficulty, the methodology relies on molecular Monte Carlo simulations of the pure N₂O₄ and NO₂, as well as on the reactive N₂O₄ ⇌ 2NO₂, enabling the determination of those missing pure-component properties and thus the calculation, on a macroscopic scale, of the reactive mixture properties. Finally, the comparison of calculated mixture properties with available experimental data leads to validate the accuracy of the proposed methodology.