Copolymers In Aqueous Solution Research Articles

Effect of Pressure on the Micellar Structure of PMMA-b-PNIPAM Diblock Copolymers in Aqueous Solution

Effect of Pressure on the Micellar Structure of PMMA-<i>b</i>-PNIPAM Diblock Copolymers in Aqueous Solution

Pronounced Cold Crystallization and Hydrogen Bonding Distortion of Water Confined in Microphases of Double Zwitterionic Block Copolymer Aqueous Solutions.

Advanced materials leveraging water control are garnering considerable interest, with the state of water emerging as a critical aspect of material design. This study explored the impact of microphase separation on water using aqueous solutions of double zwitterionic diblock copolymers, specifically poly(carboxybetaine methacrylate) and poly(sulfobetaine methacrylate) (PCB2-b-PSB4). These copolymers form a mesoscale periodic ordered lattice structure consisting of two distinct aqueous phases. Through differential scanning calorimetry and X-ray emission spectroscopy, it was found that water in these PCB2-b-PSB4 aqueous solutions exhibits pronounced cold crystallization and subtle distortions in hydrogen-bonding configurations.

Exploring the impact of cresols on aggregation characteristics of non-linear PEO-PPO-PEO block copolymers in aqueous solution

The present research investigates the intricate interplay between some industrially essential compounds, viz. 2-methylphenol (o-cresol, OC), 4-methylphenol (p-cresol, PC), 4-n-Butylphenol (BP) and non-linear ethylene oxide-propylene oxide (EO-PO) type block copolymers (Tetronics®) in aqueous solutions by employing an array of physico-chemical techniques. Each examined Tetronic® possesses 40% EO segments in its molecular structure. The study delves into the interaction and structural modifications that occur when cresols are doped into the copolymer solutions. The added cresols disrupt the hydrophilic-hydrophobic balance of Tetronics® depending on their hydrophobicities. The lowering of the cloud point (CP) is accompanied by a corresponding increase in solution viscosity. Doping of OC and PC has a dissimilar effect on viscosity compared to BP. The intermicellar interactions are adjudged to be probable cause of the unusual viscosity trend. Scattering techniques (DLS and SANS) confirm the morphology of aggregates. The results are interpreted in terms of H-bonding.

Anti-temperature anti-salinity anti-shear C18MAAC / NaAA Amphiphilic Copolymer: Preparation, characterization and properties

For improving the temperature resistance, salt resistance and shear resistance of conventional copolymers, the new hydrophobic monomer C18MAAC was prepared by substitution, then C18MAAC/NaAA amphiphilic dicopolymer was prepared by micellar polymerization. The synthetic parameters were optimized using the single-variable method: reaction temperature 50°C, mass fraction of initiators to the total monomers 0.7 wt%, mass fraction of hydrophobic monomer C18MAAC to NaAA and C18MAAC 2 wt%, and the mass fraction of two monomers 25 wt%. The structure of the C18MAAC and the C18MAAC/NaAA copolymer were characterized, and the morphology of the copolymer was observed. Effect of mass fraction of the copolymer and the salt, temperature, shear rate on viscosity of the aqueous solution were investigated. With the increase of copolymer's mass fraction, the viscosity of the aqueous solution increased slowly first, and the viscosity increases rapidly after reaching 0.4 wt% of copolymer concentration. Therefore, 0.5 wt% concentration of copolymer aqueous solution was selected in the experiment, and the rotor was selected for the rheological performance test. The results showed that the temperature resistance, salt resistance and shear resistance of the copolymer reached 90 °C, 1 wt% salt and 150 s-1 respectively. The C18MAAC/NaAA copolymer/surfactant composite system is very stable in 1wt% salt at 90 °C, and has good synergistic effect to improve the viscosity of the solution, which making it is a promising candidate as an oil-displacing agent.

How Polyoxometalate Promote the Aggregation of a Cyanine Dye in the Aqueous Solution of Non-Ionic Copolymers of Varying Hydrophilic-Lipophilic Balance?

The nonradiative pathway leading to the photoisomerization of a cyanine dye is well-established information. However, the modulations induced in the photoisomerization pathway by a Keggin-type polyoxometalate in a confined media is new. Our study reveals that, in the presence of pluronic block copolymers F-108 and P-123, phosphomolybdic acid hydrate (PMA) promotes the aggregation of 3,3'-diethylthiadicarbocyanine iodide (DTDCI). The absorption spectra show a clear indication of a red-shifted trimer band in F-108 and P-123, whereas it is absent in F-127 and P-84. Fluorescence emission studies suggest that, in the presence of PMA, the rate of photoisomerization is accelerated in F-108, P-123, and P-84 micelles, whereas it is retarded in F-127 micelles. Time-resolved studies in the presence of PMA indicate the preference of F-108, P-84, and P-123 toward the trapped conformer of DTDCI, whereas F-127 favors the formation of photoisomer of DTDCI. Our findings imply the importance of the interplay between the hydrophobic and electrostatic interactions between the DTDCI cations and the PMA anions in nonionic micelles of varying hydrophilic-lipophilic balance (HLB). Dynamic light scattering (DLS) data suggest a modulation by PMA in the intermicellar electrostatic repulsions of a hydrophilic copolymer micelle, whereas its unaffected in a hydrophobic copolymeric micelle.

INFLUENCE OF EXTERNAL FACTORS ON BINARY SYSTEMS DURING RAFT POLYMERIZATION

The article discusses the method of radical copolymerization as an effective way to obtain new polymer compounds with practically valuable properties. This method is based on the free radical mechanism, in which the sequential addition of molecules of an unsaturated monomeric compound to a growing macroradical occurs. Due to the relative simplicity of this method, it makes it possible to produce a large number of polymers for various purposes on an industrial scale. Unsaturated polyesters of various compositions and molecular weights, which can significantly affect the properties of the final products, are considered promising coreagents capable of entering into radical copolymerization reactions with vinyl monomers. The article discusses the results of studies of polymer gels obtained on the basis of unsaturated carboxylic acids. The author refers to previous studies, showing that such gels have high sorption capacity, while the starting material does not have similar properties. The following describes the structure analysis of p-PGFPh copolymers with these acids, where important characteristics such as the presence of ionized units in vinyl monomers are discussed. The significance of these studies for the creation of materials with the necessary properties of sorption and interaction with other substances. Study of the influence of environmental pH on the behavior of copolymers based on polypropylene glycol fumarate phthalate with acrylic and methacrylic acids. The equilibrium degree of swelling of the studied copolymers in aqueous solutions at different temperatures was also determined by the gravimetric method. In general, analysis of the swelling curve when varying the acidity/alkalinity of the external solution indicates that the gels we synthesized are polyelectrolytes; analysis of the curve when exposed to temperature, the resulting copolymers are thermosensitive. Thus, the main idea of the article is the importance of using unsaturated carboxylic acids to create polymer gels with high sorption capacity and emphasizes the importance of analyzing the structure of such materials to understand their properties and application possibilities.

Position Matters: Pyridine Regioisomers Influence Secondary Structure and Micelle Morphology in Polymer-Homopolypeptide Micelles.

Polymer-homopolypeptide block copolymers are a class of bioinspired materials that combine the processability and stability of synthetic polymers with the biocompatibility and unique secondary structures of peptides, such as α-helices and β-sheets. These properties make them ideal candidates for a wide variety of applications, for example, in the pharmaceutical field, where they are frequently explored as building blocks for polymeric micelle drug delivery systems. While homopolypeptide side chains can be furnished with an array of different moieties to impart the copolymers with desirable properties, such as stimulus responsivity, pyridine derivatives represent an underutilized functional group for this purpose. Additionally, the interplay between polypeptide side chain structure, secondary conformation, and micelle morphology is not yet well understood, particularly in the case of structural regioisomers. Therefore, in this work, a series of polymer-homopolypeptide copolymers were prepared from a poly(ethylene glycol)-b-poly(glutamic acid) (PEG-b-PGA) backbone, where the pendant carboxylic acid groups were covalently conjugated to a series of pyridine regioisomers by carbodiimide coupling. These pyridine regioisomers differed only in the position of the nitrogen heteroatom, ortho, meta or para, relative to the linking group, generating a series of PEG-b-poly(pyridinylmethyl glutamate) (PEG-b-PMG) copolymers. Following self-assembly of the copolymers in aqueous solutions, dynamic light scattering (DLS) revealed differences in micelle hydrodynamic diameter (Dh) (ranging from ∼60 to 120 nm), while transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) revealed distinctive morphologies ranging from ellipsoidal, to cylindrical, and disc-like, suggesting that subtle changes in positional isomers in the polypeptide block may influence the micelle structure. Analysis of the PEG-b-PMG copolymer micelles by circular dichroism (CD) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy revealed that differences in the morphology were associated with changes in polypeptide secondary structure, which in turn was influenced by the position of the pyridine heteroatom. Overall, these findings contribute to the broader understanding of the relationship between polypeptide structure and micelle morphology and serve as useful insight for the rational design of polymer-polypeptide nanoparticles.

Study on the properties of slump-retaining polycarboxylate superplasticizer synthesized by EPEG at different pH

Abstract The application of EPEG-type polycarboxylate water reducer in concrete is gradually widespread and studying its preparation process and performance comparison will help promote the EPEG market. In this study, ethylene glycol nonvinyl polyoxymethylene ether (EPEG-2400), acrylic acid (AA) and hydroxyethyl acrylate (HEA) were used as the main synthetic monomers. Under the redox initiation system of hydrogen peroxide-formaldehyde sodium bisulfite, EPEG-type water-retaining polycarboxylate water reducer was synthesized by free radical copolymerization in aqueous solution. The influence of different pH values on the dispersibility of the synthesized polycarboxylate water reducer was studied. The results show that different pH values have little influence on the molecular weight of EPEG water-retaining polycarboxylate water reducer and the work performance of EPEG-synthesized water-retaining polycarboxylate water reducer is better under neutral conditions.

Molecular Simulation Study of the Kinetics and Mechanism of Micellization of Charged and Uncharged Block Copolymer in Aqueous Solution: Polystyrene-Block-Poly(acrylic acid) PS-b-PAA

The micellization kinetics, dynamics, and diffusional properties of poly(styrene)-block-poly(acrylic acid) copolymer chains in salt-free aqueous solution have been investigated as a function of the copolymer composition (XPS ) for the cases of un-ionized (charge density f = 0) and ionized PAA blocks (charge density f = 1), for the first time to our knowledge via atomistic molecular dynamic simulations. The micelle formation mechanism was inspected by tracking the population of unimers and clusters across the simulation trajectory; it confirmed that the asymmetric copolymer micelle formation followed a combined approach of unimer insertion and cluster fusion mechanisms, while symmetric micelle formation followed the unimer insertion method exclusively. Micelle formation took a longer time for copolymers having charged (ionized) PAA blocks (f > 0) and relatively short PS blocks (number fraction of PS repeat units in copolymer XPS < 0.5) due to the presence of a greater number of hydrophobic groups, in agreement with the micellization kinetics observed for model copolymer micelles via DPD (Dissipative Particle Dynamics) simulation studies in literature. The conformational dynamics were studied using the relaxation of backbone dihedral angles and radius of gyration, for the core and corona blocks, respectively, showed that the PS blocks relaxed slower as compared to the soluble PAA blocks in solution due to their hydrophobic nature. The conformational relaxation time increased linearly for the PS blocks and was invariant for the PAA blocks with respect to XPS. The interaction dynamics of the PS-b-PAA copolymer micelles studied via the relaxation times of the PAA-PAA inter-chain (τHB,PP) and PAA-water inter-molecular hydrogen bonds (τHB,PW) showed the increase of τHB,PP, and the decrease of τHB,PW in solution with the increase in XPS. The PAA-water H-bond relaxes slower at f = 1 than that at f = 0 due to the stronger affinity of ionized PAA units with water molecules. The diffusivity of the copolymer chains decreased exponentially with an increase in XPS value, which is in agreement with the theoretical and experimental observations described in the literature.

Effect of Ionic Strength and pH on the Sorption of Heavy Metals onto Polyaniline Copolymers in Aqueous Solutions.

Polyaniline (PANI) and two copolymers, poly(aniline-co-o-toluidine) (PoTOL-50) and poly(aniline-co-o-anisidine) (PoANI-50) were synthesized with equal input ratios (1:1) to enhance PANI as sensing material for the sensing of various heavy metal analytes in aqueous solutions. The polymers were evaluated for both their sensitivity and selectivity toward four heavy metals (Ba2+, Cd2+, Cu2+, and Ni2+) and two common matrix interferents (Ca2+ and Mg2+) at 10 and 40 ppm. The effect of pH and ionic strength of the aqueous solutions on the sensitivity and selectivity was also evaluated. All three polymers showed high sensitivity and selectivity to Ba2+. Varying the pH and ionic strength of solutions did not show significant differences in either the selectivity or the sensitivity of the polymers.

Current paradigms in employing self-assembled structures: Drug delivery implications with improved therapeutic potential

Recent efforts have focused on developing improved drug delivery systems with enhanced therapeutic efficacy and minimal side effects. Micelles, self-assembled from amphiphilic block copolymers in aqueous solutions, have gained considerable attention for drug delivery. However, there is a need to further enhance their efficiency. These micelles offer benefits like biodegradability, biocompatibility, sustained drug release, and improved patient compliance. Yet, researchers must address stability issues and reduce toxicity. Nanoscale self-assembled structures have shown promise as efficient drug carriers, offering an alternative to conventional methods. Fine-tuning at the monomeric and molecular levels, along with structural modifications, is crucial for optimal drug release profiles. Various strategies, such as entrapping hydrophobic drugs and using polyethylene oxide diblock copolymer micelles to resist protein adsorption and cellular adhesion, protect the hydrophobic core from degradation. The polyethylene oxide corona also provides stealth properties, prolonging blood circulation for extended drug administration. Amphiphilic copolymers are attractive for drug delivery due to their adjustable properties, allowing control over micelle size and morphology. Emerging tools promise complex and multifunctional platforms. This article summarizes about the challenges as far as the use of micelles is concerned, including optimizing performance, rigorous pre-clinical and clinical research, and suggests further improvement for drug delivery efficacy.

Hydrogen bonding regulation on phase change in stimuli responsive copolymer aqueous solution

Hydrogen bonding (HB) is vital for the phase transition and physical properties of stimuli responsive copolymers. However, the governing mechanism remains unclear. Herein, we investigated the HB dynamics in a representative thermo-responsive copolymer (PNIPAM-AM) aqueous solution. Three types of HB were identified: polymer-polymer chain (CO:H–N), polymer chain-water molecule (CO:H–O) and water-water molecules (H–O:H–O) by vibrational spectroscopy. Increasing polymer concentration, the H–O:H–O softened and CO:H–O stiffened, leading to the destruction of HB network in water-water clusters. Upon increasing solution temperature, CO:H–O softened while CO:H–N stiffened, resolving the dehydration and cross-linking of polymer chains. Confinement of water molecules in the “cages” (∼ tens to hundreds of micrometers) after sol-gel phase transition was visualized, disclosing the mechanism of water holding capacity of PNIPAM-AM. The correlation of molecule vibration and copolymer microscopic structure was established, contributing to the fundamental understanding of phase behavior and physical properties regulations in stimuli responsive copolymer aqueous solution.

Hybrid polyionic complexes as nanoreactors for the synthesis of iron oxide nanoparticles: From size control to modulation of magnetic and catalytic properties

Hybrid polyion complexes (HPICs) obtained from the complexation in aqueous solution of a double hydrophilic block copolymers and metal ions can act as efficient precursors for the controlled synthesis of hybrid nanoparticles. Hence, HPICs based on a mixture of ferrous and ferric ions with poly(ethylene oxide)-block-poly(acrylic acid) were used to initiate, after the addition at 70 °C of a solution of NH4OH, the formation of iron oxide nanoparticles. The careful choice of the molar ratio between polymer and metal ions within HPICs enables to tune the morphology and size of the obtained iron oxide nanoparticles while maintaining the same surface composition. This control of size and composition was further used to highlight the relationship between the size of these particles and their catalytic and magnetic properties.

Hydrodynamic and Conformational Behavior of N-Vinylformamide–Sodium 4-Styrenesulfonate Copolymers in Aqueous Solutions

Hydrodynamic and Conformational Behavior of N-Vinylformamide–Sodium 4-Styrenesulfonate Copolymers in Aqueous Solutions

Synthesis and characterization of polystyrene-b-poly(vinyldipicolinic acid) pH-responsive core-shell nanoparticles

The self-assembly of a new series of amphiphilic polystyrene-b-poly(4-vinyldipicolinic acid) PS-b-PVDPA diblock copolymers in aqueous solution is reported in order to obtain core–shell nanoparticles composed of a PS core and a PVDPA shell. Diblock copolymers were synthesized by Supplemental Activation Reducing Agent-Atom Transfer Radical Polymerization (SARA-ATRP) with a degree of polymerization (DP) of the PS block in the range 112–260 and a DP of PVDPA block of 10, 30 or 50. Anionic latex nanoparticles of PS-b-PVDPA were prepared by solvent displacement methods. All the nanoparticle suspensions had a narrow size distribution (0.014 ≤ PDI ≤ 0.144) with zeta potential in the range −27 mV to −38 mV indicating electrostatic repulsions due to carboxylate anions and therefore high colloidal stability. DLS was used to determine nanoparticle size, with SEM and TEM used to determine and confirm both size and spherical shape. All three methods found the size for these nanoparticles to be in the range 75–120 nm. Using fluorimetry and DLS methods, Critical Aggregation Concentration (CAC) for each type of nanoparticle was determined to be within the range of 33–69 mg/L. Micelles were pH-responsive with stability in aqueous conditions for pH > 3.5. Micelles were stable at pH 5.5 for up to 40 days and at temperature up to 60 °C.

Formation of Hydrophobic-Hydrophilic Associates in the N-Vinylpyrrolidone and Vinyl Propyl Ether Copolymer Aqueous Solutions.

Utilizing turbidimetry data, an examination is conducted on the behavior of solutions containing N-vinylpyrrolidone and vinyl propyl ether copolymer within a temperature range coinciding with the occurrence of a phase transition. The investigation reveals that within specific conditions prevailing in this domain, the emergence of entities denoted as hydrophobic-hydrophilic associates is conceivable. These entities are characterized by the presence of a relatively dense core, upheld by hydrophobic interplays, and they are proficient in effectively dispersing irradiation within the optical spectrum. Encircling this core is a hydrophilic periphery that impedes the formation of insoluble precipitates. The development of such associates transpires when hydrophobic interactions have attained a discernible prominence, although they remain inadequate to counteract the forces that drive the expansion of macromolecular coils. Under these circumstances, the energetically favored course of action entails the constitution of a core for the aforementioned associates, involving discrete segments from diverse macromolecules. Notably, the introduction of an additional constituent (ethanol) to the solution, which selectively mitigates hydrophobic interactions, serves to stabilize the hydrophobic-hydrophilic associations.

Synthesis and Characterization of Thermoresponsive Chitosan-graft-poly(N-isopropylacrylamide) Copolymers.

Thermoresponsive chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) copolymers of different composition were synthesized by free-radical polymerization of chitosan (CS) and N-isopropylacrylamide (NIPAAm) in aqueous solution using potassium persulfate (PPS) as an initiator. By changing the molar ratio of CS:NIPAAm from 1:0.25 to 1:10 graft copolymers with a CS backbone and different amounts of PNIPAM side chains were prepared. The chemical structure of the obtained CS-g-PNIPAAm copolymers was confirmed by FTIR and 1H NMR spectroscopy. 1H NMR spectra were also used to calculate the content of attached PNIPAAm side chains. Moreover, the lower critical solution temperature (LCST) behavior of synthesized copolymers was assessed by cloud point, differential scanning calorimetry and particle size measurements. The aqueous solutions of copolymers containing ≥12 molar percent of PNIPAAm side chains demonstrated LCST behavior with the phase separation at around 29.0-32.7 °C. The intensity of thermoresponsiveness depended on the composition of copolymers and increased with increasing content of poly(N-isopropylacrylamide) moieties. The synthesized thermoresponsive chitosan-graft-poly(N-isopropylacrylamide) copolymers could be potentially applied in drug delivery systems or tissue engineering.

Self-assembly behavior of fluorinated amphiphilic copolymer in aqueous solution and its properties in the solid film state

Owing to the high electronegativity of fluorine atoms, incorporation of fluorinated moieties in a polymer can confer unique properties such as low surface energy and self-assembling ability in solution. In this study, a series of amphiphilic copolymers were prepared by radical polymerization using three monomers: 2-((2,3,3,3- tetrafluoro- 2- (1,1,2,3,3,3- hexafluoro −2- (perfluoroethoxy) propoxy) propanoyl)oxy) ethyl acrylate (FHEMA), maleic anhydride (MAH), and acrylic acid (AA). The PFHEMA block provided low surface tension, and the MAH and AA blocks (containing carboxyl) increased solubility. The properties of the polymer (PFHEMA-co-PMAH-co-PAA) can be regulated by changing the PFHEMA length. Characterization by Fourier-transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC) indicated successful polymerization (FHA01 and FHA02). When the FHEMA/MAH/AA molar ratio was 3:8:9 (FAA02), the surface tension of the hydrolyzed amphiphilic copolymers FAA02 at 300 mg·mL−1 in aqueous solution was 15.76 mN·m−1, the lowest value due to a higher fluorine content than FAA01. FAA02 self-assembled in water to form pH-sensitive micelles with diameters greater than 140 nm. For the FAA02 film, both the F/C ratio and arrangement of fluorine-containing side chains decreased with increasing film depth. Thus, this type of fluorine-containing low surface free energy material can be developed into a high performance coating material.

Synthesis of copolymer nanocomposite by in situ intercalative polymerization for batch and fixed bed adsorption

AbstractPartially neutralized acrylic acid (AA)/sodium acrylate (NaAA) and N, N′‐methylenebisacrylamide (MBA) were subjected to intercalative copolymerization in aqueous solution of polyvinyl alcohol (PVA) in the presence of sodium montmorillonite (NaMMT) nano clay to prepare filled semi‐interpenetrating network (FSIPN) type composite polymer networks. Filled Full IPN (FFIPN) composites were prepared in a similar way by additional crosslinking of PVA with maleic acid (MA) crosslinker. The polymers were characterized with FTIR, NMR, XRD, TGA, SEM, EDAX, TEM, XPS, DLS, PZC, and pH reversibility test. The synthesis variables were optimized with respect to batch adsorption of 100 mg/L each of methyl violet (MV) and congo red (CR) dye as response using the central composite design (CCD) of response surface methodology (RSM). The FFIPN prepared from polyacrylic acid (PAA)/sodium polyacrylate containing PVA/Clay/MBA/MA of optimized composition of 4/1.5/0.75/4 (wt.% of AA/NaAA), respectively, showed an optimized adsorption (mg/g adsorbent) of 459.16/417.31 of MV/CR as single dye and 438.01/417.31 of MV/CR in 1:1 binary mixtures of 100 mg/L feed concentration. The FFIPN showed an adsorption (mg/g) of 41.54/37.61 and removal% of 88.5/80.12 at a feed flow rate, bed height, and feed inlet concentration of 20 mL/min, 20 mm, and 50 mg/L, respectively.

Multitunable LCST and UCST Behaviors of Y-Junction-Bearing Polyacrylamides

Rational design of thermoresponsive polymers allows facile control over LCST/UCST and nano-object shapes. Despite tremendous progress, it remains a challenge to monitor chain conformations as the solvent isotope affects types of phase transitions. This study aims at addressing the challenge by construction of thermoresponsive Y-junction-bearing polyacrylamides with nontraditional intrinsic luminescence. With an increasing carbon number of substituents connecting with ester groups (x = 1, 2, 3, 4, 6, 8, 10, and 12), copolymers transform from hydrophilic (x = 1) to LCST (x = 2) and dual LCST/UCST (x ≥ 3) in H2O, while no UCST is available in D2O due to more stable amide–solvent hydrogen bonding and strengthened intra-/intermolecular interactions. Meanwhile, copolymer aqueous solutions can exhibit substituent/pH-dependent evolution orders of single, dual, and triple phase transitions, and asymmetric V-shaped evolution of LCST/UCST values with increasing pH is usually observed. Although 1H NMR analysis can only reveal the solvation status of subunits in the LCST region, fluorescence analysis allows to elucidate intra-/intermolecular hydrogen bonding interactions in LCST/UCST regions. Thermoinduced self-assembly in water renders sphere-to-nanocapsule-to-lamella-to-nanocapsule transitions. These important findings provide us with considerable insight into hydrogen bonding-related UCST formation by rational macromolecular design. Our study may open new avenues for regulating phase transitions and exploring solvent isotope effects.