Solvent Exchange Rates Research Articles

Solvent Exchange Dynamics in M2(dobdc): An Interplay among Binding Strength, Exchange Kinetics, and Cooperativity.

Solvent exchange is a crucial step in ensuring the complete activation of metal-organic frameworks (MOFs); however, the conditions for solvent exchange vary among MOFs, even within the isostructural variants. This study examines the factors contributing to solvent exchange by investigating the isostructural M2(dobdc) (M═Mg, Co, Zn) series. Common solvents N,N-dimethylformamide (DMF), ethanol (EtOH), and methanol (MeOH) are employed to assess the solvent exchange at coordinatively unsaturated sites (CUS) of M2(dobdc). By monitoring both solvents released from the MOF during solvent exchange and the coordination environment of metals within the MOF, a picture is constructed of exchange rates during early stages of solvent exchange as well as expulsion of the last traces of bound solvents. This differentiation is achieved by a combination of bulk monitoring of solvent phase composition and microscopic application of Raman spectroscopy on the single-crystal level. The kinetics of solvent replacement is revealed to have a substantial contribution from cooperativity; this phenomenon is observed in both the forward and reverse directions. Thermogravimetric analysis coupled with IR spectroscopy and density functional theory (DFT) calculations are employed to elucidate the relationship between solvent exchange rates and solvent binding energy. The solvent exchange rates are determined by the kinetic barriers of solvent exchange that do not follow the order of the solvent binding affinity. This work contributes to understanding the solvent exchange of MOFs by examining the interplay among the binding strength, exchange kinetics, and cooperativity. It further provides valuable insights for scrutinizing MOF activation protocols.

Testing the hypothesis that solvent exchange limits the rates of calcite growth and dissolution.

It is established that the rates of solvent exchange at interfaces correlate with the rates of a number of mineral reactions, including growth, dissolution and ion sorption. To test if solvent exchange is limiting these rates, quasi-elastic neutron scattering (QENS) is used here to benchmark classical molecular dynamics (CMD) simulations of water bound to nanoparticulate calcite. Four distributions of solvent exchanges are found with residence times of 8.9 ps for water bound to calcium sites, 14 ps for that bound to carbonate sites and 16.7 and 85.1 ps for two bound waters in a shared calcium-carbonate conformation. By comparing rates and activation energies, it is found that solvent exchange limits reaction rates neither for growth nor dissolution, likely due to the necessity to form intermediate states during ion sorption. However, solvent exchange forms the ceiling for reaction rates and yields insight into more complex reaction pathways.

From Bulk to Interface: Solvent Exchange Dynamics and Their Role in Ion Transport and the Interfacial Model of Rechargeable Magnesium Batteries.

Multivalent battery chemistries have been explored in response to the increasing demand for high-energy rechargeable batteries utilizing sustainable resources. Solvation structures of working cations have been recognized as a key component in the design of electrolytes; however, most structure-property correlations of metal ions in organic electrolytes usually build upon favorable static solvation structures, often overlooking solvent exchange dynamics. We here report the ion solvation structures and solvent exchange rates of magnesium electrolytes in various solvents by using multimodal nuclear magnetic resonance (NMR) analysis and molecular dynamics/density functional theory (MD/DFT) calculations. These magnesium solvation structures and solvent exchange dynamics are correlated to the combined effects of several physicochemical properties of the solvents. Moreover, Mg2+ transport and interfacial charge transfer efficiency are found to be closely correlated to the solvent exchange rate in the binary electrolytes where the solvent exchange is tunable by the fraction of diluent solvents. Our primary findings are (1) most battery-related solvents undergo ultraslow solvent exchange coordinating to Mg2+ (with time scales ranging from 0.5 μs to 5 ms), (2) the cation transport mechanism is a mixture of vehicular and structural diffusion even at the ultraslow exchange limit (with faster solvent exchange leading to faster cation transport), and (3) an interfacial model wherein organic-rich regions facilitate desolvation and inorganic regions promote Mg2+ transport is consistent with our NMR, electrochemistry, and cryogenic X-ray photoelectron spectroscopy (cryo-XPS) results. This observed ultraslow solvent exchange and its importance for ion transport and interfacial properties necessitate the judicious selection of solvents and informed design of electrolyte blends for multivalent electrolytes.

In Vitro and In Vivo Hydrolytic Degradation Behaviors of a Drug-Delivery System Based on the Blend of PEG and PLA Copolymers.

This paper presents the in vitro and in vivo degradation of BEPO, a marketed in situ forming depot technology used for the formulation of long-acting injectables. BEPO is composed of a solution of a blend of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) triblock and diblock in an organic solvent, where a therapeutic agent may be dissolved or suspended. Upon contact with an aqueous environment, the solvent diffuses and the polymers precipitate, entrapping the drug and forming a reservoir. Two representative BEPO compositions were subjected to a 3-month degradation study in vitro by immersion in phosphate-buffered saline at 37 °C and in vivo after subcutaneous injection in minipig. The material erosion rate, as a surrogate of the bioresorption, determined via the depot weight loss, changed substantially, depending on the composition and content of polymers within the test item. The swelling properties and internal morphology of depots were shown to be highly dependent on the solvent exchange rate during the precipitation step. Thermal analyses displayed an increase of the depot glass transition temperature over the degradation process, with no crystallinity observed at any stage. The chemical composition of degraded depots was determined by 1H NMR and gel permeation chromatography and demonstrated an enrichment in homopolymers, i.e., free PLA and (m)PEG, to the detriment of (m)PEG-PLA copolymers in both formulations. It was observed that the relative ratio of the degradants within the depot is driven by the initial polymer composition. Interestingly, in vitro and in vivo results showed very good qualitative consistency. Taken together, the outcomes from this study demonstrate that the different hydrolytic degradation behaviors of the BEPO compositions can be tuned by adjusting the polymer composition of the formulation.

The regulation of surface nanobubble generation via solvent exchange on different substrates

Surface nanobubbles (SNBs) play an essential role in fluid transport, interfacial reactions, electrochemistry, material fabrication, surface cleaning, etc. Controllable preparation of SNBs is very crucial for their applications, such as controlling material preparation and increasing the efficiency of surface cleaning. Ethanol-water exchange, as a typical example of solvent exchange, is one of the most widely used methods to produce SNBs. By controlling the conditions, it is possible to manipulate the size and number density of nanobubbles. In this work, we systematically investigated the formation of SNBs on hydrophobic and hydrophilic surfaces by ethanol-water exchange at different rates using atomic force microscopy. Results indicate that the exchange rate has a significant effect on the size and number density of SNBs. On both hydrophobic surface of highly oriented pyrolytic graphite (HOPG) and hydrophilic surface of mica, formed nanobubbles exhibit smaller sizes and higher number density with increased exchange rates. But at the same solvent exchange rate, SNBs generated on HOPG surface were in greater number and width than on mica, while their heights change much less. To understand the effect of exchange rate on nanobubble production, we proposed a mechanism of non-uniform nucleation and diffusion-driven growth. A simulation of the gas concentration near SNBs was performed, and the results show good agreement between numerical calculations and experimental data. We believe that our results will contribute to the understanding of nanobubble generation and stabilization processes. It also provides a new perspective on the factors that affect the generation of SNBs, which allows the production and application of nanobubbles to be controlled in a reliable manner.

Self-assembled zein organogels as in situ forming implant drug delivery system and 3D printing ink

Recently, biomedical applications of organogels have been increasing; however, there is a demand for bio-based polymers. Here, we report self-assembled zein organogels in N-methyl pyrrolidone (NMP), Dimethyl sulfoxide (DMSO), and glycerol formal (GF). The gel formation was driven by the solvent’s polarity and the hydrogen bonding component of Hansen Solubility Parameters was important in promoting gelation. Gels exhibited shear-thinning and thixotropic properties. Furthermore, water-induced self-assembly of zein allows mechanically robust in situ implant formation by solvent exchange. Ciprofloxacin was incorporated as a model drug and sustained release depending upon the solvent exchange rate was observed. In situ implants in agarose gel retained antibacterial efficacy against S. aureus for more than 14 days. Zein-based organogels were further applied as 3D printing ink and it was found that zein gel in DMSO had superior printability than gels prepared in NMP and GF. Using three solvents to prepare organogels can enable the encapsulation of various drugs and facilitate the preparation of composite gels with other biocompatible polymers. These organogel systems can further be used for developing 3D printed drug delivery systems or scaffolds for tissue engineering.

Nanobowls from Amphiphilic Core–Shell Cyclic Bottlebrush Polymers

Cyclic bottlebrush polymers are macrocycles that contain pendent side-chain polymers on nearly every repeat unit. We leveraged a method to generate cyclic bottlebrush polymers utilizing ring-expansion polymerization (REP) followed by subsequent grafting-from via atom-transfer radical polymerization (ATRP) to produce core–shell cyclic bottlebrush polymers and investigated their self-assembly behavior in water. The bottlebrush polymers were comprised of a cyclic backbone with side chains composed of a hydrophobic polystyrene block and a hydrophilic poly(acrylic acid) block. A two-step morphological transformation from spheres to porous spheres to nanobowls (spheres with a single large pore) was observed with solvent exchange from tetrahydrofuran to water. In contrast, under identical experimental conditions, an analogous linear bottlebrush polymer with a similar backbone and side chain degrees of polymerizations did not aggregate into nanobowls but rather exhibited a porous sphere morphology. These unusual morphologies and their propensities to transform can be attributed to changes in the internal viscosity of the aggregates during the solvent exchange process. Additionally, the rate of solvent exchange was found to influence the propensity for shape transformation to occur.

Stochastic Model of Solvent Exchange in the First Coordination Shell of Aqua Ions.

Ion microsolvation is a basic, yet fundamental, process of ionic solutions underlying many relevant phenomena in either biological or nanotechnological applications, such as solvent reorganization energy, ion transport, catalytic activity, and so on. As a consequence, it is a topic of extensive investigations by various experimental techniques, ranging from X-ray diffraction to NMR relaxation and from calorimetry to vibrational spectroscopy, and theoretical approaches, especially those based on molecular dynamics (MD) simulations. The conventional microscopic view of ion solvation is usually provided by a “static” cluster model representing the first ion–solvent coordination shell. Despite the merits of such a simple model, however, ion coordination in solution should be better regarded as a complex population of dynamically interchanging molecular configurations. Such a more comprehensive view is more subtle to characterize and often elusive to standard approaches. In this work, we report on an effective computational strategy aiming at providing a detailed picture of solvent coordination and exchange around aqua ions, thus including the main structural, thermodynamic, and dynamic properties of ion microsolvation, such as the most probable first-shell complex structures, the corresponding free energies, the interchanging energy barriers, and the solvent-exchange rates. Assuming the solvent coordination number as an effective reaction coordinate and combining MD simulations with enhanced sampling and master-equation approaches, we propose a stochastic model suitable for properly describing, at the same time, the thermodynamics and kinetics of ion–water coordination. The model is successfully tested toward various divalent ions (Ca2+, Zn2+, Hg2+, and Cd2+) in aqueous solution, considering also the case of a high ionic concentration. Results show a very good agreement with those issuing from brute-force MD simulations, when available, and support the reliable prediction of rare ion–water complexes and slow water exchange rates not easily accessible to usual computational methods.

Initial Leuprolide Acetate Release from Poly(d,l-lactide-co-glycolide) in Situ Forming Implants as Studied by Ultraviolet-Visible Imaging.

The initial drug release from in situ forming implants is affected by factors such as the physicochemical properties of the active pharmaceutical ingredient, the type of the excipients utilized, and the surrounding environment. The feasibility of UV-vis imaging for characterization of the initial behavior of poly(d,l-lactide-co-glycolide) (PLGA)/1-methyl-2-pyrrolidinone (NMP) in situ forming implants was investigated. The in vitro release of leuprolide acetate (LA) and implant formation in real time were monitored using dual-wavelength imaging at 280 and 525 nm, respectively, in matrices based on agarose gel and hyaluronic acid (HA) solution emulating the subcutaneous matrix. Three hours upon injection of the pre-formulation, approximately 15% of the total amount of LA administered was found in the agarose gel, while 5% was released from the implant into the HA solution. Concurrently, more extensive swelling of the implants in the HA solution as compared to implants in the agarose gel was observed. Transport of both LA and the solvent NMP was investigated using UV-vis imaging in a small-scale cell where the geometry of the formulation was controlled, showing a linear correlation between drug release and solvent escape. Light microscopy showed that the microstructures of the resulting implants in agarose gel and HA solution were different, which may be attributed to the different solvent exchange rates. UV imaging was also used to examine the interaction of LA with the release medium by characterizing the diffusion of LA in agarose gel, HA solution, and phosphate buffered saline. The reduced LA diffusivity in HA solution as compared to agarose gel and the LA distribution coefficient in the agarose gel-HA system indicated the presence of interactions between LA and HA. Our findings show that the external environment affects the solvent exchange kinetics for in situ forming implants in vitro, resulting in different types of initial release behavior. UV-vis imaging in combination with biorelevant matrices may offer an interesting approach in the development of in situ forming implant delivery systems.

Sensitivity enhancement of homonuclear multidimensional NMR correlations for labile sites in proteins, polysaccharides, and nucleic acids

Multidimensional TOCSY and NOESY are central experiments in chemical and biophysical NMR. Limited efficiencies are an intrinsic downside of these methods, particularly when targeting labile sites. This study demonstrates that the decoherence imparted on these protons through solvent exchanges can, when suitably manipulated, lead to dramatic sensitivity gains per unit time in the acquisition of these experiments. To achieve this, a priori selected frequencies are encoded according to Hadamard recipes, while concurrently subject to looped selective inversion or selective saturation procedures. Suitable processing then leads to protein, oligosaccharide and nucleic acid cross-peak enhancements of ≈200–1000% per scan, in measurements that are ≈10-fold faster than conventional counterparts. The extent of these gains will depend on the solvent exchange and relaxation rates of the targeted sites; these gains also benefit considerably from the spectral resolution provided by ultrahigh fields, as corroborated by NMR experiments at 600 MHz and 1 GHz. The mechanisms underlying these experiments’ enhanced efficiencies are analyzed on the basis of three-way polarization transfer interplays between the water, labile and non-labile protons, and the experimental results are rationalized using both analytical and numerical derivations. Limitations as well as further extensions of the proposed methods, are also discussed.

Assessing Site-Specific Enhancements Imparted by Hyperpolarized Water in Folded and Unfolded Proteins by 2D HMQC NMR.

Hyperpolarized water can be a valuable aid in protein NMR, leading to amide group 1H polarizations that are orders of magnitude larger than their thermal counterparts. Suitable procedures can exploit this to deliver 2D 1H–15N correlations with good resolution and enhanced sensitivity. These enhancements depend on the exchange rates between the amides and the water, thereby yielding diagnostic information about solvent accessibility. This study applied this “HyperW” method to four proteins exhibiting a gamut of exchange behaviors: PhoA(350–471), an unfolded 122-residue fragment; barstar, a fully folded ribonuclease inhibitor; R17, a 13.3 kDa system possessing folded and unfolded forms under slow interconversion; and drkN SH3, a protein domain whose folded and unfolded forms interchange rapidly and with temperature-dependent population ratios. For PhoA4(350–471) HyperW sensitivity enhancements were ≥300×, as expected for an unfolded protein sequence. Though fully folded, barstar also exhibited substantial enhancements; these, however, were not uniform and, according to CLEANEX experiments, reflected the solvent-exposed residues. R17 showed the expected superposition of ≥100-fold enhancements for its unfolded form, coexisting with more modest enhancements for their folded counterparts. Unexpected, however, was the behavior of drkN SH3, for which HyperW enhanced the unfolded but, surprisingly, enhanced even more certain folded protein sites. These preferential enhancements were repeatedly and reproducibly observed. A number of explanations—including three-site exchange magnetization transfers between water and the unfolded and folded states; cross-correlated relaxation processes from hyperpolarized “structural” waters and labile side-chain protons; and the possibility that faster solvent exchange rates characterize certain folded sites over their unfolded counterparts—are considered to account for them.

Role of Water Molecules in Protein–Ligand Dissociation and Selectivity Discrimination: Analysis of the Mechanisms and Kinetics of Biomolecular Solvation Using Molecular Dynamics

The mechanism by which water molecules modulate biomolecular interactions and the time scale of microscopic solvation processes are usually not known. This is particularly problematic as it prevents the incorporation of effects of water molecules into the design of drug molecules with optimal binding kinetics and selectivity. We investigated this crucial problem of drug discovery using trypsin and thrombin in complex with benzamidine and N-amidinopiperidine. For these systems, we studied the mechanism and time scale of solvation using molecular dynamics and umbrella sampling calculations. In thrombin, water molecules are seemingly stable in the apo binding pocket and have an exchange rate on the nanosecond time scale. On the contrary, water molecules in apo trypsin exchange approximately one order of magnitude faster than in thrombin. This difference in the exchange rate is due to internal water channels that are only found in thrombin linking the interior of the binding pocket with bulk solvent. These cause the exchange rate of water molecules to be independent of the ligand molecule. However, in the case of trypsin, the solvent exchange rate greatly varies between the two complexes, indicating a strong dependence on the ligand molecule. Furthermore, the binding mechanism of the ligand molecules critically depends on water molecules that intercalate between key amino acids and the ligand, leading to enhanced water residence times in intermediate dissociation steps. Our findings strongly indicate a selectivity discriminating role of water molecules for these two proteins and underline the functional interplay between water channels and binding affinity of ligand molecules.

BEPO®: Bioresorbable diblock mPEG-PDLLA and triblock PDLLA-PEG-PDLLA based in situ forming depots with flexible drug delivery kinetics modulation

This article presents BEPO®, an in situ forming depot (ISFD) technology mediated by a solvent-exchange mechanism. The matrix of the in situ formed drug delivery depot is composed of the combination of a diblock (DB) and a triblock (TB) polyethylene glycol-polyester copolymer. This combination offers a broad capability to tune the release of a wide variety of drugs to the desired pharmacokinetics. The work described in the present article demonstrates that the delivery rate and profile can be adjusted by changing the composition of either TB or DB or the relative ratio between them, among other parameters. It has been shown that the polymeric composition of the formulation has a substantial impact on the solvent exchange rate between the organic solvent and the surrounding aqueous medium which subsequently determines the internal structure of the resulting depot and the delivery of the therapeutic cargo. This has been demonstrated studying the in vitro release of two model molecules: bupivacaine and ivermectin.Formulations releasing these drugs have been administered to animal models to show the possibility of delivering therapeutics from weeks to months by using BEPO® technology.

Highly Stable FAxMA1 − xPbI3 − xBrx–2P Precursor for Crystalizing High‐Quality, Large‐Area Perovskite Film in an Ambient Atmosphere

Perovskite solar cells (PSCs) are one of the highly promising new‐generation photovoltaic technologies. One of the remaining challenges for commercializing PSCs is to prepare high‐quality, large‐area perovskite films in an ambient atmosphere reproducibly using less toxic materials. Herein, a nonvolatile, less toxic substance, 2‐pyrrolidinone (2P), is used as a complexant solvent for the perovskite precursor solution. Combining this with a newly developed spin‐assisted solvent extraction (SASE) crystallization method, a high‐quality perovskite film is prepared in air reproducibly. The nonvolatile nature of 2P and the formation of MAI–PbI2–2P adduct widen the time window for antisolvent engineering, and SASE enhances the solvent exchange rate of the precursor film to form a high‐quality perovskite film in air. An inverted cell (based on the postsolvent‐treated perovskite absorber) exhibits a power conversion efficiency of more than 18%. This film preparation method is feasible for depositing a high‐quality mixed‐cation or mixed‐cation, mixed‐halide perovskite film on both PEDOT:PSS and TiO2 surfaces to fabricate inverted and regular PSCs, respectively, to achieve efficiencies of more than 16%. More importantly, high‐quality, large‐area MAPbI3 film is prepared reproducibly in air for fabricating perovskite submodules to achieve an efficiency of 14% (verified at 13.04% after the cell is packed for efficiency evaluation).

Investigation of the Amide Proton Solvent Exchange Properties of Glycosaminoglycan Oligosaccharides.

One-dimensional 1H NMR experiments were conducted for aqueous solutions of glycosaminoglycan oligosaccharides to measure the amide proton temperature coefficients and activation energy barriers for solvent exchange and evaluate the effect of pH on the solvent exchange properties. A library of mono- and oligosaccharides was prepared by enzymatic depolymerization of amide-containing polysaccharides and by chemical modification of heparin and heparan sulfate saccharides including members that contain a 3- O-sulfated glucosamine residue. The systematic evaluation of this saccharide library facilitated assessment of the effects of structural characteristics, such as size, sulfation number and site, and glycosidic linkage, on amide proton solvent exchange rates. Charge repulsion by neighboring negatively charged sulfate and carboxylate groups was found to have a significant impact on the catalysis of amide proton solvent exchange by hydroxide. This observation leads to the conclusion that solvent exchange rates must be interpreted within the context of a given chemical environment. On their own, slow exchange rates do not conclusively establish the involvement of a labile proton in a hydrogen bond, and additional supporting experimental evidence such as reduced temperature coefficients is required.

Exchangeable deuterons introduce artifacts in amide 15N CEST experiments used to study protein conformational exchange.

Protein molecules sample different conformations in solution and characterizing these conformations is crucial to understanding protein function. 15N CEST experiments are now routinely used to study slow conformational exchange of protein molecules between a 'visible' major state and 'invisible' minor states. These experiments have also been adapted to measure the solvent exchange rates of amide protons by exploiting the one bond deuterium isotope effect on the amide 15N chemical shifts. However at moderately high temperatures (~ 50°C) that are sometimes required to populate protein minor conformers to levels (~ 1%) that can be detected by CEST experiments solvent H/D exchange can lead to 'dips' in low B115N CEST profiles that can be wrongly assigned to the conformational exchange process being characterized. This is demonstrated in the case of ~ 18kDa T4 Lysozyme (T4L) at 50°C and the ~ 11kDa E. coli hibernation promoting factor (HPF) at 52°C. This problem is trivially solved by eliminating the exchangeable deuterons in the solvent by using either an external D2O lock or by using a small amount (~ 1-3%) of a molecule like d6-DMSO that does not contain exchangeable deuterons to lock the spectrometer.

Measuring Solvent Hydrogen Exchange Rates by Multifrequency Excitation 15N CEST: Application to Protein Phase Separation.

Solvent exchange rates provide important information about the structural and dynamical properties of biomolecules. A large number of NMR experiments have been developed to measure such rates in proteins, the great majority of which quantify the buildup of signals from backbone amides after initial perturbation of water magnetization. Here we present a different approach that circumvents the main limitations that result from these classical hydrogen exchange NMR experiments. Building on recent developments that enable rapid recording of chemical exchange saturation transfer (CEST) pseudo-3D data sets, we describe a 15N-based CEST scheme for measurement of solvent exchange in proteins that exploits the one-bond 15N deuterium isotope shift. The utility of the approach is verified with an application to a 236 residue intrinsically disordered protein domain under conditions where it phase separates and a second application involving a mutated form of the domain that does not phase separate, establishing very similar hydrogen exchange rates for both samples. The methodology is well suited for studies of hydrogen exchange in any 15N-labeled biomolecule. A discussion of the merits of the CEST experiment in relation to the popular CLEANEX-PM scheme is presented.

Macromol. Theory Simul. 5/2017

Front Cover: The channel membrane was successfully prepared by simulations for the first time. Dissipative particle dynamics (DPD) was used to simulate the block copolymer self-assembly with the non-solvent induced phase separation (SNIPS) method and effects of polymer concentration, block ratio and solvent exchange rate on the polymer self-assembly process were investigated. This is reported by Chu Wang, Xuebo Quan, Mingrui Liao, Libo Li, and Jian Zhou* in article number 1700027.

Development of Pharmaceutically Acceptable Crystalline Forms of Drug Substances via Solid-State Solvent Exchange

In the pharmaceutical industry, solid form screening plays an important role to discover forms that exhibit desired physicochemical properties for drug product development. This work describes an approach to meet this objective by the transformation of undesirable solvates to hydrates or cosolvates with water via solid-state solvent exchange. Case studies of two drug substances, imatinib mesylate and linagliptin, are discussed, where linaglipitin methanol/ethanol solvate was converted to an iso-structural hydrate and, similarly, imatinib mesylate methanol–water cosolvate was converted to a predominantly water-containing cosolvate. Through quality by design based optimization, temperature and relative humidity were identified as critical process parameters that impacted the rate of solvent exchange during humidification. In addition, crystallization parameters that impacted the crystal size were found to play a key role in determining the extent of solvent exchange. This unexpected effect of crystal size w...

Computer Simulations on the Channel Membrane Formation by Nonsolvent Induced Phase Separation

The formation of channel membrane of polystyrene‐block‐poly(4‐vinyl pyridine) block copolymer is studied by computer simulations with the nonsolvent induced phase separation (SNIPS) method. Dissipative particle dynamics is employed to study the microphase separation process and the SNIPS mechanism. Simulation results indicate that polymer concentration has a significant effect on the membrane structure. Channel membranes form in the copolymer concentration range of 44–58%. Block ratio plays an important role in shaping the membrane structure. Solvent exchange rate also affects the degree of microphase separation at each evolution stage of simulation. The time evolution of morphologies shows that the microphase separation processes happen with the following sequences: the polymer self‐assembled and many small pores appear, then they form irregular cavities and cross‐link gradually, finally the channel membrane forms. These results throw light on the formation mechanism of polymer membranes and provide insightful guidance for future membrane design and preparation.