Polar Solvents Research Articles

An Advanced Twin-Screw Granulation Technology: The use of Non-Volatile Solvents with High Solubilizing Capacity

PurposeTwin-screw wet granulation (TSWG) is a manufacturing process that offers several advantages for the processing of water-insoluble active pharmaceutical ingredients (APIs) and has been used for increasing the solubility and dissolution rates. Here we introduce a novel TSWG approach with reduced downstream processing steps by using non-volatile solvents as granulating binders.MethodsHerein, TSWG was carried out using Transcutol a non-volatile protic solvent as a granulating binder and dissolution enhancer of ibuprofen (IBU) blends with cellulose polymer grades (Pharmacoat® 603, Affinisol™, and AQOAT®).ResultsThe physicochemical characterisation of the produced granules showed excellent powder flow and the complete transformation of IBU into the amorphous state. Dissolution studies presented immediate release rates for all IBU formulations due to the high drug-polymer miscibility and the Transcutol solubilising capacity.ConclusionsOverall, the study demonstrated an innovative approach for the development of extruded granules by processing water-insoluble APIs with non-volatile solvents for enhanced dissolution rates at high drug loadings.Graphical

Push-Pull Fluorescent Dyes with Trifluoroacetyl Acceptor for High-Fidelity Sensing of Polarity and Heterogeneity of Lipid Droplets.

Imaging and sensing of lipid droplets (LDs) attracted significant attention due to growing evidence for their important role in cell life. Solvatochromic dyes are promising tools to probe LDs' local polarity, but this analysis is biased by their non-negligible emission from intracellular membranes and capacity to emit from both the apolar core and polar interface of LDs. Here, we developed two push-pull solvatochromic dyes based on naphthalene and fluorene cores bearing an exceptionally strong electron acceptor, the trifluoroacetyl group. The latter was found to boost the optical properties of the dyes by shifting their absorption and emission to red and increasing their extinction coefficient, photostability, and sensitivity to solvent polarity (solvatochromism). In contrast to classical solvatochromic dyes, such as parent aldehydes and reference Nile Red, the new dyes exhibited strong fluorescence quenching by millimolar water concentrations in organic solvents. In live cells, the trifluoroacetyl dyes exhibited high specificity to LDs, whereas the parent aldehydes and Nile Red showed a detectable backgrounds from intracellular membranes. Experiments in model lipid membranes and nanoemulsion droplets confirmed the high selectivity of new probes to LDs in contrast to classical solvatochromic dyes. Moreover, the new probes were found to be selective to the LDs oil core, where they can sense lipid unsaturation and chain length. Their ratiometric imaging in cells revealed strong heterogeneity in polarity within LDs, which covered the range of polarities of unsaturated triglyceride oils, whereas Nile Red failed to properly estimate the local polarity of LDs. Finally, the probes revealed that LDs core polarity can be altered by fatty acid diets, which correlates with their chain length and unsaturation.

Solvent and Temperature Dependencies of the Rates of Thermal Cis-to-Trans Isomerization of Tetra-(ortho)substituted 4-Aminoazobenzenes Containing 2,6-Dimethoxy Groups.

The kinetics of thermal cis-to-trans isomerization of two tetra-(ortho)substituted 4-aminoazobenzene derivatives containing 2,6-dimethoxy groups in the 4-aminobenzene ring and either 2',6'-dimethyl (1) or 2',6'-dichloro groups in another ring was studied in 16 and 9 solvents, respectively, at room temperature. In addition, the kinetics of isomerization of 1 was studied at variable temperatures in 6 solvents. The solvent effects were analyzed in terms of multiparameter correlations using the Kamlet-Taft, Catalan, and Laurence scales. The temperature dependencies were analyzed in terms of the isokinetic relationship by using Exner's method. The correlation analysis was also extended to several previously reported systems, including isomerization of unsubstituted 4-aminoazobenzene and push-pull 4-NR2-4'-NO2 azobenzenes. It was established that for all 4-aminoazobenzenes in contrast to push-pull azobenzenes, the increase in solvent dipolarity does not affect or even inhibit isomerization rates; however, the increase in solvent acidity induces large rate accelerations. The isokinetic relationship holds only in aprotic solvents, while in alcohols and water, the temperature dependencies do not pass through the common point at T = Tiso, indicating different mechanisms operating in protic and aprotic solvents. The acceleration effect by protic solvents does not represent a type of general acid catalysis as follows from the small solvent isotope effect kH/kD = 1.26 in water. It is suggested that protic solvents induce a change in the reaction mechanism supposedly from inversion to rotation by hydrogen bonding stabilization of the negative charge developed on the azo group in a resonance structure involving a 4-amino group.

Solvatomorphism in a series of copper(II) complexes with the 5-phenylimidazole/perchlorate system as ligands.

In the course of an investigation of the supramolecular behaviour of copper(II) complexes with the 5-phenylimidazole/perchlorate ligand system (`blend') remarkable solvatomorphism has been observed. By employing a variety of crystallization solvents (polar protic, polar/non-polar aprotic), a series of 12 crystalline solvatomorphs with the general formula [Cu(ClO4)2(LH)4]·x(solvent) have been obtained [LH = 5-phenylimidazole, x(solvent) = 3.3(H2O) (1), 2(methanol) (2), 2(ethanol) (3), 2(1-propanol) (4), 2(2-propanol) (5), 2(2-butanol) (6), 2(dimethylformamide) (7), 2(acetone) (8), 2(tetrahydrofurane) (9), 2(1,4-dioxane) (10), 2(ethyl acetate) (11) and 1(diethyl ether) (12)]. The structures have been solved using single-crystal X-ray diffraction and the complexes were characterized by thermal analysis and infrared spectroscopy. The solvatomorphs are isostructural (triclinic, P1), with the exception of compound 9 (monoclinic, P21/n). The supramolecular structures and the role of the various solvents is discussed. All potential hydrogen-bond functionalities, both of the [Cu(ClO4)2(LH)4] units and of the solvents, are utilized in the course of the crystallization process. The supramolecular assembly in all structures is directed by strong recurring Nimidazole-H...Operchlorate motifs leading to robust scaffolds composed of the [Cu(ClO4)2(LH)4] host complexes. The solvents are located in channels and, with the exception of the disordered waters in 1 and the diethyl ether in 12, participate in hydrogen-bonding formation with the [Cu(ClO4)2(LH)4] complexes, serving as both hydrogen-bond acceptors and donors (for the polar protic solvents in 2-6), or solely as hydrogen-bond acceptors (for the polar/non-polar aprotic solvents in 7-11), linking the complexes and contributing to the stability of the crystalline compounds.

Importance of Polarizable Embedding for Computing Optical Rotation: The Case of Camphor in Ethanol.

Solvation effects on optical rotation are notoriously challenging to model for computational chemistry, as the specific rotatory power of a molecule can vary wildly going from apolar to polar or even protic solvents. To address such a problem, we present a polarizable embedding implementation of an electric and magnetic response property based on density functional theory and the AMOEBA polarizable force field, and apply such an implementation to the study of the optical rotation of camphor in ethanol. By comparing a continuum model, and electrostatic and polarizable embedding QM/MM models, we observe that accounting for the environment's polarization gives rise to not only a different quantitative prediction, in very good agreement with experiments for the QM/AMOEBA model, but also to a very different qualitative picture, with the values of the optical rotation computed along a classical molecular dynamics trajectory with electrostatic embedding being statistically uncorrelated to the ones obtained with the polarizable description.

Pegylated Phosphine Ligands in Iridium(I) Catalyzed Hydrogen Isotope Exchange Reactions in Aqueous Buffers.

The synthesis of a water-soluble, phosphine-pegylated iridium(I) catalyst and its application in hydrogen isotope exchange (HIE) reactions in buffer is reported. The longer polyethylene glycol side chains on the phosphine increased the water solubility independently from the pH. HIE reactions of polar substrates in protic solvents were studied. DFT calculations gave further insights into the catalytic processes. The scope and limitation of the pegylated catalyst was studied in HIE reactions of several complex compounds in borax buffer at pH 9 and the best conditions were applied in a tritium experiment with the drug telmisartan.

Chlorine-Modified Soluble Melem-Based Graphitic Carbon Nitrite: Facile Synthesis, Catalytic Property and Ultrafast 2D IR Spectroscopic Characterization.

On the basis of thermal etching bulk graphitic carbon nitride (g-C3N4), a mild hydrochloric acid treatment method was used in this work to produce g-C3N4 nano-sheets (CNNS) and further carbon nitride with chloride-modification (CNCl). The latter has thinner layer and smaller particle size and exhibit greatly improved dispersibility and solubility in water, DMSO and other polar solvents. A typical photocatalytic reaction in solution driven by CNCl shows a significantly improved photocatalytic performance over bulk g-C3N4 and CNNS. Steady-state analytical tools including SEM, mass, UV-Vis, and IR spectroscopies, and time-resolved two-dimensional infrared (2D IR) vibrational spectroscopy, were used together in this work. Better solubility, more flexible structure, smaller size, easier generation of free radicals and lower recombination rate of electron-hole pair, are believed to be reasons for the superior photocatalytic performance of CNCl.

Solid-Phase Synthesis of Well-Defined Multiblock Copolymers by Atom Transfer Radical Polymerization.

Solid-phase polymer synthesis, historically rooted in peptide synthesis, has evolved into a powerful method for achieving sequence-controlled macromolecules. This study explores solid-phase polymer synthesis by covalently immobilizing growing polymer chains onto a poly(ethylene glycol) (PEG)-based resin, known as ChemMatrix (CM) resin. In contrast to traditional hydrophobic supports, CM resin's amphiphilic properties enable swelling in both polar and nonpolar solvents, simplifying filtration, washing, and drying processes. Combining atom transfer radical polymerization (ATRP) with solid-phase techniques allowed for the grafting of well-defined block copolymers in high yields. This approach is attractive for sequence-controlled polymer synthesis, successfully synthesizing di-, tri-, tetra-, and penta-block copolymers with excellent control over the molecular weight and dispersity. The study also delves into the limitations of achieving high molecular weights due to confinement within resin pores. Moreover, the versatility of the method is demonstrated through its applicability to various monomers in organic and aqueous media. This straightforward approach offers a rapid route to developing tailored block copolymers with unique structures and functionalities.

Co‐Solvent Assisted Optimization of the CuSCN Hole Transport Layer for Enhancing the Efficiency of Ambient Processable Perovskite Solar Cells with Carbon Counter Electrodes

In recent perovskite solar cell (PSC) research, copper(I) thiocyanate (CuSCN) is an emerging inorganic hole transport layer (HTL) due to its suitable band gap, matched band edge positions with the perovskite and high stability under ambient conditions. However, being a coordination polymer typically requires sulfide‐based solvents that strongly interact with Cu(I) for dissolution. Dipropyl sulfide (DPS) is generally used where it is very sparingly soluble of about 10–12 mg mL−1, which leads to low surface coverage with pin‐holes on the surface responsible for the generation of defects at the perovskite–HTL interface. In this study, addition of the optimized amount 100 μL of co‐solvent Acetonitrile (ACN) increased the CuSCN dissolution from 10 to 35 mg mL−1. ACN can act as a Lewis‐base making it capable of donating electrons to a Lewis‐acid like Cu+ from CuSCN. ACN is a polar aprotic solvent due to its highly polar CN bond and by adding CuSCN the dipole–dipole interactions can stabilize the CuSCN molecules in solution. The device with architecture (FTO/c‐TiO2/mp‐TiO2/MAPbI3/CuSCN/carbon) showed the higher power conversion efficiency (PCE) of ≈11% with Voc of 1.01 V and Isc 24.65 mA cm−2 showing excellent stability stored under ambient atmosphere which retains 80% of its initial efficiency after 10 days.

Dioxygen Activation by Gold(I)-Distorted Porphyrin Dinuclear Complexes.

Interactions between gold-based materials and dioxygen (O2) have motivated researchers to understand reaction mechanisms for O2 activation by homo- and heterogeneous gold catalysts. In this work, gold(I) porphyrin dinuclear complexes were synthesized with a saddle-distorted porphyrin ligand. The gold(I) porphyrin complexes showed unprecedented O2 activation in the presence of protic solvents to form gold(III) tetradentate porphyrin complexes. Mechanistic insights into the O2 activation by the gold(I) center were elucidated by spectroscopic measurements and theoretical calculations, revealing that dissociation of halides on the gold(I) center by alcohol solvents and hydrogen bonding of an N-H proton in the distorted porphyrin with dioxygen played important roles in establishing the unique reactivities of gold(I) complexes.

A Fluorescent Organic Probe for Naked-Eye Detection of Chloromethanes.

An organic fluorescent probe (OFP-TAR) with a propeller-like structure was designed and synthesized. The photoluminescence of OFP-TAR in solution exhibited a significant red shift with the increase of solvent polarity, enabling a transition of fluorescence emission from blue (445 nm) to yellow (540 nm). The organic thin-film materials based on OFP-TAR/PMMA exhibit significant color changes upon exposure to CH2Cl2, CHCl3, and CCl4, with their maximum fluorescence wavelengths measured at 445, 471, and 494 nm respectively. The device facilitates the visual detection of chloromethanes and is capable of enduring more than 7 cycles of testing. These materials can also be prepared as binary-coded microarray data storage devices or applied in the field of anti-counterfeiting. The quantum yields of guest-loaded crystals CH2Cl2@OFP-TAR, CHCl3@OFP-TAR and CCl4@OFP-TAR are observed as 19.13 %, 8.79 %, and 0.83 % respectively, which are consistent with the tendency of OFP-TAR in CH2Cl2 (47.30 %), CHCl3 (34.27 %) and CCl4 (3.10 %). The fluorescence properties of OFP-TAR, OFP-TAR/PMMA, guest-loaded and guest-free crystals provided insights into the special response mechanism of OFP-TAR towards different chloromethanes.

Substituent Controlled Tunable Fluorescence from Green to Red and pH Stimuli‐Induced Reversible Fluorescence Switching in Triphenylamine–Quinoxaline Derivatives

A series of triphenylamine‐quinoxaline donor‐acceptor (bipolar) compounds (TPA‐QH, TPA‐QMe, TPA‐QCOOH and TPA‐QNO2) with different substituents were synthesized and investigated their fluorescence properties, including stimuli‐induced fluorescence responses in solution and the solid‐state. Single crystal structural analysis revealed non‐planar molecular conformation, substituent controlled intermolecular interactions and molecular packing in the crystal lattice. TPA‐QH, TPA‐QMe, TPA‐QCOOH and TPA‐QNO2 showed tunable solid‐state emission from green to red. TPA‐QH showed strong fluorescence at 487 nm (quantum yield (Φf) = 28.3%) whereas NO2 substituted TPA‐QNO2 exhibited relatively weak fluorescence at 610 nm (Φf = 4.3%). Density functional theoretical (DFT) calculations also indicated reduction of optical bandgap with substituting electron withdrawing group. The donor‐acceptor structure with intramolecular charge transfer (ICT) resulted solvent polarity dependent fluorescence tuning. The presence of acid responsive quinoxaline group was utilized to demonstrate pH‐responsive fluorescence switching and dual state fluorescence was utilized for fabricating rewritable fluorescent platform. Thus, the present study provides a structural insight to develop dual state emissive triphenylamine–quinoxaline based bipolar materials for optoelectronic applications.

Analysis of Phytochemical Compounds and Antioxidant Activity From Non-Polar to Polar Solvent Extracts In Several Types of “Basa Genep” Constituent Spices

Analysis of Phytochemical Compounds and Antioxidant Activity From Non-Polar to Polar Solvent Extracts In Several Types of “Basa Genep” Constituent Spices

Identification, screening and molecular mechanisms of natural stable angiotensin-converting enzyme (ACE) inhibitory peptides from foxtail millet protein hydrolysates: a combined in silico and in vitro study.

The stability of bioactive peptides under various food processing conditions is the basis for their use in industrial manufacturing. This study aimed to identify natural ACE inhibitors with excellent stability and investigate their physicochemical properties and putative molecular mechanisms. Five novel ACE inhibitory peptides (QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ) were isolated and identified using RP-HPLC and Nano LC-MS/MS with foxtail millet protein hydrolysates as the raw material. These peptides are non-toxic and exhibit strong ACE inhibitory activity in vitro (IC50 values between 0.13 mg mL-1 and 0.56 mg mL-1). In addition to QDPLFPL, FPGVSPF, SPAQLLPF, LVPYRP, and WYWPQ have excellent human intestinal absorption. Compared to FPGVSPF and SPAQLLPF, the stable helical structure of LVPYRP and WYWPQ allows them to maintain high stability under conditions that mimic gastrointestinal digestion and various food processing (temperatures, pH, sucrose, NaCl, citric acid, sodium benzoate, Cu2+, Zn2+, K+, Mg2+, Ca2+). The results of molecular docking and molecular dynamics simulation suggest that LVPYRP has greater stability and binding capacity to ACE than WYWPQ. LVPYRP might attach to the active pockets (S1, S2, and S1') of ACE via hydrogen bonds and hydrophobic interactions, then compete with Zn2+ in ACE to demonstrate its ACE inhibitory activity. The binding of LVPYRP to ACE enhances the rearrangement of ACE's active structural domains, with electrostatic and polar solvation energy contributing the most energy to the binding. Our findings suggested that LVPYRP derived from foxtail millet protein hydrolysates has the potential to be incorporated into functional foods to provide antihypertensive benefits.

A comparative study of two α-L-rhamnosidases with high sequence identity

The GH78 α-L-rhamnosidase from Aspergillus tubingensis (AT-Rha) was proved to be a new clade of Aspergillus α-L-rhamnosidases in the previous study. A putative α-L-rhamnosidase from A. kawachii IFO 4308 (AK-Rha) has 92 % identity in amino acid sequence with AT-Rha. In this study, AK-Rha was expressed in P. pastoris and characterized. Similar to AT-rRha, the recombinant AK-Rha (AK-rRha) showed a narrow substrate specificity to naringin. Interestingly, the enzyme activity of AK-rRha was 0.816 U/mg toward naringin, significantly lower than 125.142 U/mg of AT-rRha. Their large differences in catalytic efficiency was mainly due to their differences in kcat values between AK-rRha (0.67 s−1) and AT-rRha (4.89 × 104 s−1). The molecular dynamics simulation exhibited that the overall conformation of AK-Rha was rigid and that of AT-Rha was flexible; the Loop Y-L located above the catalytic domain formed different steric hindrances to naringin, and interacted with the flavonoid matrices at different strengths. The polar solvation energy analysis implied that the glycosidic bond was more easily hydrolysed in AT-Rha. The comparative study verified that the main feature of AK-Rha and AT-Rha represented Aspergillus α-L-rhamnosidase was the narrow substrate specificity toward naringin, and provided an insight of the relationships between their catalytic abilities and structures.

Influence of Solvent Polarity on the Conformer Ratio of Bicalutamide in Saturated Solutions: Insights from NOESY NMR Analysis and Quantum-Chemical Calculations.

The study presents a thorough and detailed analysis of bicalutamide's structural and conformational properties. Quantum chemical calculations were employed to explore the conformational properties of the molecule, identifying significant energy differences between conformers. Analysis revealed that hydrogen bonds stabilise the conformers, with notable variations in torsion angles. Conformers were classified into 'closed' and 'open' types based on the relative orientation of the cyclic fragments. NOE spectroscopy in different solvents (CDCl3 and DMSO-d6) was used to study the conformational preferences of the molecule. NOESY experiments provided the predominance of 'closed' conformers in non-polar solvents and a significant presence of 'open' conformers in polar solvents. The proportions of open conformers were 22.7 ± 3.7% in CDCl3 and 59.8 ± 6.2% in DMSO-d6, while closed conformers accounted for 77.3 ± 3.7% and 40.2 ± 6.2%, respectively. This comprehensive study underscores the solvent environment's impact on its structural behaviour. The findings significantly contribute to a deeper understanding of conformational dynamics, stimulating further exploration in drug development.

Unravelling the effect of soxhlet extracted Pisolithus arhizus fungi in bio-sensitized solar cells in response to diverse polar solvents

The potential application of Pisolithus arhizus fungi as an effective sensitizer in bio-sensitized solar cells (BSSCs) is the first of its kind to investigate the photovoltaic performance of BSSCs in polar protic and aprotic solvents. The soxhlet extraction method was employed to extract dye molecules in organic solvents including chloroform, 2-propanol, acetone, ethanol, methanol and DMSO and named PA1, PA2, PA3, PA4, PA5, PA6 to fabricate BSSCs. TiO2 and Platinum were used as working and counter electrodes. The structural, optical, morphological properties of the extracted dyes and dye anchored TiO2 films were analyzed through FTIR, UV–Vis spectroscopy and FESEM analysis. The optical absorption analysis revealed the presence of pisoquinone pigments in the fungi, from flavonoid family. The current-voltage, electrochemical impedance and cyclic voltammetry analysis showed that the PA4 ethanolic-based BSSC demonstrated the highest power conversion efficiency of 1.31 % compared to other DSSCs, with a Jsc of 3.40 mA cm−2 and Voc of 514 mV and the bandgap energy of 1.8eV. The order of the conversion efficiency for DSSCs with different solvents was ethanol (PA4) > methanol (PA5) > acetone (PA3) > DMSO (PA6) > 2-propanol (PA2) > chloroform (PA1). This finding highlights that selecting optimal, novel sensitizers and extraction solvents is crucial to maximize solar cell efficiency.

Solvation vs concentration fluctuations: confined dilute electrolytes near demixing at constant potential

In a recent paper, the effect of concentration fluctuations in a simple fully symmetric model of dilute electrolyte, confined between two planar electrodes, was investigated using constant charge simulations in the vicinity of the solute-solvent demixing transition. In agreement with previous theoretical findings it was shown that the total capacitance was enhanced by the occurrence of concentration fluctuations. In this work we will resort to constant potential simulations to show that the same effect is to be found in the differential capacitance. Additionally, here we will consider the effects of ion solvation by a polar solvent modelled by TIP4P/2005 water. Finally, the original fully symmetric ionic solute will be replaced by a three-site coarse grained model for a well know room temperature ionic liquid, 1-butyl-3-methyl-imidazolium tetrafluoroborate ([BMI] + [BF 4 ] − )). Our results show the presence of strong local fields within the capacitor due to incomplete local screening, and a marked asymmetry in the charge distribution. The expected capacity enhancement due to concentration fluctuations is completely mitigated by solvation effects and the response of the polar solvent to the external field.

A solution for 4-propylguaiacol hydrodeoxygenation without ring saturation

We investigate solvent effects in the hydrodeoxygenation of 4-propylguaiacol (4PG, 166 amu), a key lignin-derived monomer, over Ru/C catalyst by combined operando synchrotron photoelectron photoion coincidence (PEPICO) spectroscopy and molecular dynamics simulations. With and without isooctane co-feeding, ring-hydrogenated 2-methoxy-4-propylcyclohexanol (172 amu) is the first product, due to the favorable flat adsorption configuration of 4PG on the catalyst surface. In contrast, tetrahydrofuran (THF)—a polar aprotic solvent that is representative of those used for lignin solubilization and upgrading—strongly coordinates to the catalyst surface at the oxygen atom. This induces a local steric hindrance, blocking the flat adsorption of 4PG more effectively, as it needs more Ru sites than the tilted adsorption configuration revealed by molecular dynamics simulations. Therefore, THF suppresses benzene ring hydrogenation, favoring a demethoxylation route that yields 4-propylphenol (136 amu), followed by dehydroxylation to propylbenzene (120 amu). Solvent selection may provide new avenues for controlling catalytic selectivity.

Fabrication and Efficient Interfacial Assembly of Bright Red-Emitting Carbon Quantum Dots for Security-Warning Textiles.

Carbon quantum dots (CQDs) have attracted more attentions due to their multiple performances. However, the fabrication of long-wavelength emitting CQDs with aliphatic precursors still remains a challenge, mainly because it is difficult to generate large sp2 domains to reduce energy gap, which is not conducive to a redshift of the luminescence peak. Hereon, by regulating the pH of citric acid and thiourea mixture, a N, S co-doped CQD emitting bright red fluorescence at 635nm is successfully fabricated through the solvothermal reaction under acidic condition, achieving a high quantum yield of 32.66%. Solvatochromic effects of the CQDs are discussed through theoretical equations and models, which confirm that the hydrogen-bonding interaction dominates the fluorescence emission behavior of CQDs in polar solvents. Besides, a feasible strategy is proposed to prepare an anti-counterfeiting textile via the deposition of red-emitting CQDs onto cotton fibers, through rapidly evaporating the preferred organic solvent. As expected, the CQD-decorated textiles exhibit encouraging anti-counterfeiting and security-warning functions, along with underwater and long-distance detectability, washability, and sun resistance. It is worth noting that the present work is innovative in realizing the application of red-light-emitting CQDs in the fields of security-warning textiles.