Solvent Pairs Research Articles

Colloidal Dispersions of Sterically and Electrostatically Stabilized PbS Quantum Dots: Structure Factors, Second Virial Coefficients, and Film-Forming Properties.

Electrostatically stabilized nanocrystals (NCs) and, in particular, quantum dots (QDs) hold promise for forming strongly coupled superlattices due to their compact and electronically conductive surface ligands. However, studies of the colloidal dispersion and interparticle interactions of electrostatically stabilized sub-10 nm NCs have been limited, hindering the optimization of their colloidal stability and self-assembly. In this study, we employed small-angle X-ray scattering (SAXS) experiments to investigate the interparticle interactions and arrangement of PbS QDs with thiostannate ligands (PbS-Sn2S64-) in polar solvents. The study reveals significant deviations from the ideal solution behavior in electrostatically stabilized QD dispersions. Our results demonstrate that PbS-Sn2S64- QDs exhibit long-range interactions within the solvent, in contrast to the short-range steric repulsion characteristic of PbS QDs with oleate ligands (PbS-OA). Introducing highly charged multivalent electrolytes screens electrostatic interactions between charged QDs, reducing the length scale of the repulsive interactions. Furthermore, we calculated the second virial (B2) coefficients from SAXS data, providing insights into how surface chemistry, solvent, and size influence pair potentials. Finally, we explore the influence of long-range interparticle interactions of PbS-Sn2S64- QDs on the morphology of films produced by drying or spin-coating colloidal solutions. The long-range repulsive term of PbS-Sn2S64- QDs promotes the formation of amorphous films, and screening the electrostatic repulsion by the addition of an electrolyte enables the formation of crystalline domains. These findings highlight the critical role of NC-NC interactions in tailoring the properties of functional materials made of colloidal NCs.

Photo‐Mediated RAFT Step‐Growth Polymerization With Diacrylate Monomers: Investigating Versatility and Oxygen Tolerance

AbstractPhotomediated reversible addition fragmentation chain transfer (RAFT) step‐growth polymerization is performed using a trithiocarbonate‐based chain transfer agent (CTA) and acrylate‐based monomers both with and without a photocatalyst. The versatility of photo‐mediated RAFT step‐growth is demonstrated by one‐pot synthesis of a graft copolymer via sequential monomer addition. Furthermore, oxygen‐tolerant photo‐mediated RAFT step‐growth is demonstrated, facilitated by the appropriate selection of photocatalyst and solvent pair (zinc tetraphenyl porphyrin [ZnTPP] and dimethyl sulfoxide [DMSO]), enabling ultralow volume polymerization under open‐air conditions.

Study of Manipulative In Situ Pore-Formation upon Polymeric Coating on Cylindrical Substrate for Sustained Drug Delivery.

Herein, the micro-porous polylactic acid coating applied on the surface of the cylindrical substrate is fabricated by a novel in situ pore-formation strategy based on the combinational effect of breath figure (BF) and vapor-induced phase separation (VIPS) processes. Under the condition of high environmental humidity, solvent pair of chloroform and dimethylformamide is employed for post-treatment onto pre-formed PLA coating to induce the pore-formation following the mechanism of BF and VIPS, respectively. A composite porous structure with both cellular-like and bi-continuous network morphologies is obtained. By tunning the experimental factors including the ratio of the solvent pair, environmental humidity, and temperature, morphological manipulation upon the pore morphology can be facilely achieved based on the control of mechanism transition between BF and VIPS. Paclitaxel is used as a model drug and loaded into the porous coating by the wicking effect of post-immersion. Coatings with different morphological features show varying drug loading and release capacities. The 28-day release test reveals dynamic release profiles between different coating samples, with the total release rate ranging from 35.70% to 79.96%. Optimal loading capacity of 19.28µg cm-2 and 28-day release rate of 35.70% are achieved for the coating with composite BF-VIPS structure. This research established a cost-efficient strategy with high flexibility in the structural manipulation concerning the construction of drug-eluting coating with the feature of manipulative drug delivery.

P-Phenylenediamine-derived carbon nanodots for probing solvent interactions.

Carbon nanodots, the luminescent nanoparticles of carbon with size restriction below 10 nm, have attracted inordinate attention in materials science due to their widespread applications in optoelectronic and biological fields. Low toxicity and facile synthesis pathways render them favourites in the above-mentioned areas in the context of green chemistry. This work presents fine applications of p-phenylenediamine-derived carbon nanodots (PD-CNDs) achieved via a facile one-pot hydrothermal method. Adequate characterization using X-ray diffraction and spectroscopic and microscopic studies confirmed spherical particles with an average particle size of 2.8 nm, functionalised with amino, carboxyl, and hydroxyl groups. The carbon framework was functionalised with pyridinic and pyrrolic nitrogens. Upon 365 nm UV light illumination, an aqueous dispersion of PD-CNDs showed red-orange fluorescence. Detailed spectral analysis using UV-visible absorption and fluorescence spectroscopy identified edge states and surface groups as luminescent centres, with a significant contribution arising from the latter. The investigation conducted using a collection of solvents, categorized into polar and nonpolar, indicated the potential of the system for applications based on its solvatochromic nature. The feature enabled the determination of different polarity parameters of the solvents, as well as dielectric constants of solvents and solvent mixtures, with considerable accuracy. The system was potent for predicting the composition of a given pair of solvents. The service of the system is also extended for moisture sensing in organic solvents within an error percentage < 1. High quantum yield values (0.61) combined with solvent composition-dependent optical features ensure broader applications of the system to probe solvent interactions.

Swelling of Polypropylene Separators and Its Effect on the Lithium-Ion Battery Performance

The safety of lithium-ion batteries (LIBs) depends on separators -- porous materials providing ionic transport between the electrodes while preventing them from direct contact. Many commercial separator materials are polymers, e.g., polypropylene. Polypropylene has a non-polar structure, so it tends to interact favorably with non-polar solvents, such as carbonates used in LIBs as electrolyte solvents. These favorable interactions result in two effects: separator plasticization (softening) [1] and swelling [2]. Both swelling and plasticization affect the battery performance and cause safety concerns.Here we present a model which predicts the swelling of a porous polymer separator based on the molecular structures of the polymer and the solvent. The model is based on Flory's theory of polymer solutions and the Flory–Huggins parameter for polymer–solvent interactions. We introduced two additional parameters to Flory's theory, taking into account the complex structure of the porous polymers. These two parameters can be obtained from experimental data on two solvents. The Flory–Huggins parameter is calculated based on the UNIFAC-FV group contribution method for a given polymer–solvent pair. Our model predicts swelling of polypropylene separators in various solvents, matching the experimental data [3] quite well. By relating the swelling of the separator to the change in its porosity and tortuosity, we estimated the increase of cell impedance as a result of the swelling.Finally, the plasticization of the separator makes it less persistent to mechanical impacts, increasing the chances of failure. Since the solvent-induced plasticization of the separator is correlated with its swelling [3], our model can also be utilized to assess this effect. Therefore, our model can be used to quickly evaluate various polymer–solvent pairs for application in lithium-ion batteries.1. Sheidaei, A.; Xiao, X.; Huang, X.; Hitt, J. Mechanical behavior of a battery separator in electrolyte solutions. J. Power Sources 2011, 196, 8728−8734.2. Cannarella, J.; Liu, X. Y.; Leng, C.; Sinko, P.; Gor, G. Y.; Arnold, C. B. Mechanical properties of a battery separator under compression and tension. J. Electrochem. Soc. 2014, 161, F3117−F3122.3. Gor, G. Y.; Cannarella, J.; Leng, C. Z.; Vishnyakov, A.; Arnold, C. B. Swelling and softening of lithium-ion battery separators in electrolyte solvents. J. Power Sources 2015, 294, 167−172.4. Maksimov, A. V.; Molina, M.; Maksimova, O. G.; Gor, G. Y. Prediction of Swelling of Polypropylene Separators and Its Effect on the Lithium-Ion Battery Performance. ACS Appl. Polym. Mater. 2023, 5(3), 2026-2031.

Solvent-pair surfactants enabled assembly of clusters and copolymers towards programmed mesoporous metal oxides

Organic-inorganic molecular assembly has led to numerous nano/mesostructured materials with fantastic properties, but it is dependent on and limited to the direct interaction between host organic structure-directing molecules and guest inorganic species. Here, we report a “solvent-pair surfactants” enabled assembly (SPEA) method to achieve a general synthesis of mesostructured materials requiring no direct host-guest interaction. Taking the synthesis of mesoporous metal oxides as an example, the dimethylformamide/water solvent pairs behave as surfactants and induce the formation of mesostructured polyoxometalates/copolymers nanocomposites, which can be converted into metal oxides. This SPEA method enables the synthesis of functional ordered mesoporous metal oxides with different pore sizes, structures, compositions and tailored pore-wall microenvironments that are difficult to access via conventional direct organic-inorganic assembly. Typically, nitrogen-doped mesoporous ε-WO3 with high specific surface area, uniform mesopores and stable framework is obtained and exhibits great application potentials such as gas sensing.

Solvent modulation strategy for Sb-based anode to achieve stable potassium storage

High-concentration electrolyte (HCE) and localized high-concentration electrolyte (LHCE) strategies have been successfully developed for potassium-ion batteries (PIBs) to address the interface incompatibility issue, especially for the high-theoretical-capacity antimony (Sb)-based alloy-typed anode suffering from the drastic volume expansion problem. However, the high costs along with special solvents for these electrolytes significantly limits their widespread applications in PIBs. Herein, a new dilute electrolyte of 1 M KFSI in a mixed solvent of ethylene carbonate (EC) and 1, 2-dimethoxyethane (DME) (1:1 v/v) is developed to stabilize the K-storage kinetics of Sb anodes. The mixed solvent of common ester and ether promotes the formation of stable K+-EC solvent pair and thus generates a robust solid-electrolyte-interphase (SEI) for stable K-storage. As a result, the fabricated Sb@NC anode exhibits a stable capacity of 376 mAh/g after 100 cycles at 100 mA g−1, which is comparable to that in the HCE of 5 M KFSI/DME. These results demonstrated that low-cost and high-compatibility electrolytes for alloy-typed anodes can be achieved via rational design of the solvation structures for dilute electrolytes, resulting into stable K-storage properties and huge prospects of commercialized applications.

Tunable Non-Kasha Behaviors and Excited-State Dynamics of Quadrupolar Squaraine Aggregates.

Versatile coupling theories have been developed for rationalizing unusual aggregation phenomena of multipolar chromophores. Here, diverse excitonic couplings of a quadrupolar squaraine dye protonated by trifluoroacetic acid could be achieved and tuned unprecedentedly in different solvation media. Subtle changes of the solvent and ion pair influenced the aggregation of the donor-acceptor-donor (D-A-D)-type SQC6 and led to significant variations in optical properties. In contrast to conventional H/J aggregates, strong spectroscopic evidence of nonfluorescent and red-shifted hJ aggregation was obtained. Assumptions of the excitonic interplay with variable strength stabilized by the synergic contributions of π-π stacking and electronic interaction were addressed. Comparative excited-state dynamics in the aggregates clarified the distinctive excitonic coupling of adjacent quadrupolar molecules and the nature of the excited state beyond the dimers. Meanwhile, dominant two-photon absorption transitions could be elucidated by a resonance-enhanced mechanism. The present unusual molecular interplay provides a strategy to fine tune the optical properties of multipolar aggregates.

Ranking of dispersive-extraction solvents pairs with TOPSIS for the extraction of mifepristone in water samples using dispersive liquid-liquid microextraction

TOPSIS, known as Technique for Order of Preference by Similarity to Ideal Solution, is an example of a multi-criteria decision analysis (MCDA) tools useful for decision making for ranking or selecting alternatives based on multiple criteria. In this study, rankings of dispersive-extraction solvents used in DLLME for the extraction of mifepristone in tap water samples was performed to assess their greenness. Two TOPSIS methods based on the objective mean weight (TOPSIS-MW) and entropy (TOPSIS-Entropy) weighting methods were proposed. Criteria were divided into three main categories describing different analytical perspectives: analytical performance, solvents greenness, and combination of analytical performance and solvent greenness. The properties and safety data of the solvents, mean detector response and coefficient of variance were considered as attributes to rank the greener solvent pairs from the combination of sixteen different extraction and disperser solvents as alternatives. The best overall analytical performance for mifepristone was for dichloroethane-acetone and chlorobenzene-tetrahydrofuran pair of solvents, weighted by mean and entropy weights, respectively. The assessment of solvents greenness showed that chloroform-acetone was the most favourable option in terms of green chemistry. The first rank in the combination of the two group of assessment criteria was also achieved by chloroform-acetone solvents. The performance of TOPSIS-MW and TOPSIS-Entropy was evaluated against that of simple additive weighting (SAW) weighted by mean and entropy in terms of the performance of LC-QTOF-MS. The methods were found to be closely correlated with some leading precisely to similar ranking observations.

Prediction of Swelling of Polypropylene Separators and Its Effect on the Lithium-Ion Battery Performance

The safety and reliability of lithium-ion batteries depend on porous separators, many of which are made of polymer materials, such as polypropylene. Favorable interactions between a separator and organic electrolyte solvents used in the batteries often induce separator swelling. Swelling increases the electric resistance of the cell and is accompanied by plasticization of the separator, which also affects the battery’s performance. Here we propose a model based on Flory’s theory of polymer solutions which can predict the swelling of a porous polymer separator based on the Flory–Huggins parameter for polymer–solvent interactions. Despite the complexity of the polymer structure, introducing only two additional parameters provides predictive capability for the model. These two parameters can be obtained based on experimental measurements of separator swelling in two different solvents; the model also requires the Flory–Huggins parameter as an input, which can be calculated based on the UNIFAC-FV group contribution method for a given polymer–solvent pair. We illustrated the applicability of this model to recent experimental data on the swelling of polypropylene separators in various solvents. We also showed a simple relation between the separator swelling and an increase in cell resistance. Our model can be used for a quick assessment of various polymer–solvent pairs for application in lithium-ion batteries.

Demonstration of Solute-specific Synergism in Binary Solvents.

The structure and solvation behavior of binary liquid mixtures of Methanol (MeOH) and N, N-Dimethylformamide (DMF) are explored by ascertaining their intermolecular interactions with either Rhodamine-B (RhB) or Rhodamine101 (Rh101) dye through steady-state absorption, emission, and two-photon induced fluorescence. Specifically, in the present investigation, we examine the strong synergistic solvation observed for the combinations of hydrogen bond donating (MeOH) and accepting (DMF) solvent pairs. Solvatochromism causes the solvatochromic probe molecules to sense increased polarity compared to their bulk counterparts. The origin of synergism was explained in terms of solute-solvent and solvent-solvent interactions in binary solvent mixtures interactions, as evidenced by probe dependence. The solvation behavior of the Methanol and DMF binary solvent mixture shows strong probe dependence, with Rh101 showing synergism while RhB does not.

Solvent and H/D Isotopic Substitution Effects on the Krichevskii Parameter of Solutes: A Novel Approach to Their Accurate Determination

We establish a direct route for the accurate determination of the solvent effect on the Krichevskii parameter of a solute, based solely on the contrasting solvation behavior of the solute in the desired solvent relative to that of the reference solvent, i.e., in terms of the distinct solvation Gibbs free energies of the solute and the corresponding Krichevskii parameters of an ideal gas solute in the pair of solvents. First, we illustrate the proposed approach in the determination of the H/D−solvent effect on the Krichevskii parameter of gaseous solutes in aqueous solutions, when the solvents are different isotopic forms (isotopomers) of water, and then, by generalizing the approach to any pair of solvents. For that purpose, we (a) identify the links between the standard solvation Gibbs free energy of the i−solute in the two involved solvent environments and the resulting Krichevskii parameters, (b) discuss the fundamentally based linear behavior between the Krichevskii parameter and the standard solvation Gibbs free energy of the i−solute in an α−solvent, and interpret two emblematic cases of solutions involving either an ideal gas solute or an i−solute behaving identically as the solvating species, as well as (c) provide a novel microstructural interpretation of the solvent effect on the Krichevskii parameter according to a rigorous characterization of the critical solvation as described by a finite unambiguous structure making/breaking parameter Siα∞(SR) of the i−solute in the pair of α−solvents.

Absolute molar mass determination in mixed solvents. 2. SEC/MALS/DRI in a mix of two “nearly-isovirial” solvents

The accurate determination of polymer molar mass (M) averages and distributions via size-based separation methods employing mixed solvents remains one of the great macromolecular characterization challenges. This is due to the possibility for preferential solvation, whereby the region in the immediate vicinity of the polymer in solution becomes enriched in one of the solvents as compared to this solvent's fractional amount in the mix. In such cases, the chromatographic baselines of differential detectors such as light scattering photometers and differential refractometers no longer provide a quantitative reflection of the solvents' contribution to the heights of individual peak slices, thereby introducing error into molar mass calculations. The problem is addressed here through the use of a “nearly-isovirial” solvent pair. The second virial coefficient (A2) of both solvents being nearly equal for the polymers analyzed means that preferential solvation is obviated. The accuracy of this approach is shown via analysis by size-exclusion chromatography with on-line multi-angle static light scattering and differential refractometry detection (SEC/MALS/DRI), for a trio of narrow-dispersity polystyrene (PS) standards covering a nearly 40-fold range in M. In a mix of two nearly isovirial solvents, namely tetrahydrofuran (THF) and toluene, calculated molar mass averages and distributions are shown to be essentially identical across the range of solvent ratios. Polymer size is likewise shown to be constant with solvent ratio in this scenario. This is contrasted with the same polymers dissolved in a mix of the non-isovirial, non-isorefractive solvents THF and dimethylformamide (DMF). Results from this latter set of experiments show the large error in calculated M that results from preferential solvation, which can be as high as ≈ 1 × 105 g mol−1 for an 8 × 105 g mol−1 narrow-dispersity polystyrene. It is determined that, for a 25:75 THF:DMF mix, the solvent ratio in the immediate vicinity of the polymers examined “flips” to ≈75:25 THF:DMF due to preferential solvation.

Hitherto Unknown Solvent and Anion Pairs in Solvation Structures Reveal New Insights into High-Performance Lithium-Ion Batteries.

Solvent‐solvent and solvent‐anion pairings in battery electrolytes have been identified for the first time by nuclear magnetic resonance spectroscopy. These hitherto unknown interactions are enabled by the hydrogen bonding induced by the strong Lewis acid Li+, and exist between the electron‐deficient hydrogen (δ +H) present in the solvent molecules and either other solvent molecules or negatively‐charged anions. Complementary with the well‐established strong but short‐ranged Coulombic interactions between cation and solvent molecules, such weaker but longer‐ranged hydrogen‐bonding casts the formation of an extended liquid structure in electrolytes that is influenced by their components (solvents, additives, salts, and concentration), which in turn dictates the ion transport within bulk electrolytes and across the electrolyte‐electrode interfaces. The discovery of this new inter‐component force completes the picture of how electrolyte components interact and arrange themselves, sets the foundation to design better electrolytes on the fundamental level, and probes battery performances.

Accurate Binding Free Energy Method from End-State MD Simulations.

Herein, we introduce a new strategy to estimate binding free energies using end-state molecular dynamics simulation trajectories. The method is adopted from linear interaction energy (LIE) and ANI-2x neural network potentials (machine learning) for the atomic simulation environment (ASE). It predicts the single-point interaction energies between ligand–protein and ligand–solvent pairs at the accuracy of the wb97x/6-31G* level for the conformational space that is sampled by molecular dynamics (MD) simulations. Our results on 54 protein–ligand complexes show that the method can be accurate and have a correlation of R = 0.87–0.88 to the experimental binding free energies, outperforming current end-state methods with reduced computational cost. The method also allows us to compare BFEs of ligands with different scaffolds. The code is available free of charge (documentation and test files) at https://github.com/otayfuroglu/deepQM.

Solvent selection for polymers enabled by generalized chemical fingerprinting and machine learning.

We present machine learning models trained on experimental data to predict room-temperature solubility for any polymer-solvent pair. The new models are a significant advancement over past data-driven work, in terms of protocol, validity, and versatility. A generalizable fingerprinting method is used for the polymers and solvents, making it possible, in principle, to handle any polymer-solvent combination. Our data-driven approach achieves high accuracy when either both the polymer and solvent or just the polymer has been seen during the training phase. Model performance is modest though when a solvent (in a newly queried polymer-solvent pair) is not part of the training set. This is likely because the number of unique solvents in our data set is small (much smaller than the number of polymers). Nevertheless, as the data set increases in size, especially as the solvent set becomes more diverse, the overall predictive performance is expected to improve.

Nickel-Based Inks for Flexible Electronics — A Review on Recent Trends

Inkjet printing (IJP) is an efficient, simple, scalable and low-cost additive manufacturing technique for the deposition of functional materials on substrates used in flexible electronic devices, sensors, and light-emitting diodes to name a few. Nanoparticle ink, metal oxide decomposition (particle-free ink), polymer ink, and semiconductor ink are classifications of the inks used in IJP. Effective printing of the material is possible when the ink parameters (viscosity, particle size, surface tension) and its derived dimensionless quantities (Weber number, Reynolds’ number, and Ohnesorge number) fall within a desirable range. The formation of the coffee-ring effect during the post-printing process is one of the major concerns, which affects the morphology and electrical conductivity of the printed pattern. In this review, a summary of recent developments of Ni-based inks in terms of formulation, sintering and properties is presented, along with the effect of combining Ni with other materials such as NiO, Ag, Cu, Zn, Fe, carbon, and rare earth metals on the film properties. The precursors and solvents used for the Ni ink preparation, along with the additives and surfactants, have been presented to understand their impact on the film’s properties and develop a design to choose the ideal precursor–solvent pair. Finally, the challenges in formulating inks and the necessity to develop a model to optimize the choice of solvent/ precursor are presented. The model would improve the selection of additives and precursors and reduce material wastage and enhance performance with fewer defects.

Small difference between the nonlinear refractions of normal and deuterated solvents measurable by nonlinear ellipse rotation

In this work, we have measured the nonlinear refractions of six different normal and deuterated solvents: water, DMSO, methanol, acetone, toluene, and chloroform using a nonlinear ellipse rotation (NER) signal with femtosecond laser pulses. High-precision, self-referenced NER measurements could detect small differences between the refractive nonlinearities of normal and deuterated solvents. We observed that the replacement of hydrogen with deuterium atoms slightly reduces the magnitude of the nonlinearity. Basically, the reduction is related to the amount of hydrogen and the replacement by deuterium atoms in the molecules; in this way, toluene (chloroform) presents the major (minor) difference. By measuring the nonlinear refraction as a function of the pulse width, we also could observe that the refractive nonlinearity increases as the pulse gets longer. Using a simple empirical model, we could discriminate the ultrafast electronic and delayed orientational refractive nonlinearities of these six pairs of solvents.

Isolation of natural caffeine from liptonâ„¢ black tea through acid-base liquid-liquid extraction approach, its medical significance and its characterization by thin layer chromatography and IR analysis

To isolate the caffeine from Liptonâ„¢ Black Tea Brand, a sequence of practices was applied. An Acid-Base Liquid-Liquid Extraction approach carried out to force the caffeine to be isolated in upper organic layer as extractant. By this method, first caffeine was isolated from tea bags through passing different steps of extraction, then caffeine was isolated from tea with the use of both Solid-Liquid approach as well as liquid-liquid extraction approach. A product of 0.05 g of pure caffeine was obtained giving the percentage yield or percent recovery of 1.22%. Calculated percent recovery was 1.2 %, this percentage yield clarified that in this tea brand, very small caffeine is investigated, this deduces a significant loss of product throughout the procedure which are due to formation of emulsions and not due to washing thoroughly with DCM to extract maximum yield. It is also significant to be considered that reactions of precursor with solvent pair may not be completed, so 100% yield is not conceivable. Due to much transfers in all processes, this loss might be occurred. Due to much transfers in all processes, this loss might be occurred that’s why repeated the process three times again. It is also revealed that as much water was added which decreased the concentration of Caffeine. On analysis with IR, Peak at f=3000Hz indicates the presence of -NH2 and -CONH2 groups while the peaks at f=1600 Hz and f=1750 Hz indicates the presence of alkene portion of the caffeine molecule which concluded that Caffeine is a purine base. Â

Exploring the Role of Anti-solvent Effects during Washing on Active Pharmaceutical Ingredient Purity.

Washing is a key step in pharmaceutical isolation to remove the unwanted crystallization solvent (mother liquor) from the active pharmaceutical ingredient (API) filter cake. This study looks at strategies for optimal wash solvent selection, which minimizes the dissolution of API product crystals while preventing the precipitation of product or impurities. Selection of wash solvents to avoid both these phenomena can be challenging but is essential to maintain the yield, purity, and particle characteristics throughout the isolation process. An anti-solvent screening methodology has been developed to quantitatively evaluate the propensity for precipitation of APIs and their impurities of synthesis during washing. This is illustrated using paracetamol (PCM) and two typical impurities of synthesis during the washing process. The solubility of PCM in different binary wash solutions was measured to provide a basis for wash solvent selection. A map of wash solution composition boundaries for precipitation for the systems investigated was developed to depict where anti-solvent phenomena will take place. For some crystallization and wash solvent combinations investigated, as much as 90% of the dissolved PCM and over 10% of impurities present in the PCM saturated mother liquor were found to precipitate out. Such levels of uncontrolled crystallization during washing in a pharmaceutical isolation process can have a drastic effect on the final product purity. Precipitation of both the product and impurities from the mother liquor can be avoided by using a solvent in which the API has a solubility similar to that in the mother liquor; for example, the use of acetonitrile as a wash solvent does not result in precipitation of either the PCM API or its impurities. However, the high solubility of PCM in acetonitrile would result in noticeable dissolution of API during washing and would lead to agglomeration during the subsequent drying step. Contrarily, the use of n-heptane as a wash solvent for a PCM crystal slurry resulted in the highest amount of precipitation among the solvent pairs evaluated. This can be mitigated by designing a multi-stage washing strategy where wash solutions of differing wash solvent concentrations are used to minimize step changes in solubility when the mother liquor and the wash solvent come into contact.