Polar Solvents Research Articles

Directionality Reversal and Shift of Rotational Axis in a Hemithioindigo Macrocyclic Molecular Motor.

Molecular motors are central driving units for nanomachinery, and control of their directional motions is of fundamental importance for their functions. Light-driven variants use easy to provide, easy to dose, and waste-free fuel with high energy content, making them particularly interesting for applications. Typically, light-driven molecular motors work via rotations around dedicated chemical bonds where the directionality of the rotation is dictated by the steric effects of asymmetry in close vicinity to the rotation axis. In this work, we show how unidirectional rotation around a virtual axis can be realized by reprogramming a molecular motor. To this end, a classical light-driven motor is restricted by macrocyclization, and its intrinsic directional rotation is transformed into a directional rotation of the macrocyclic chain in the opposite direction. Further, solvent polarity changes allow to toggle the function of this molecular machine between a directional motor and a nondirectional photoswitch. In this way, a new concept for the design of molecular motors is delivered together with elaborate control over their motions and functions by simple solvent changes. The possibility of sensing the environmental polarity and correspondingly adjusting the directionality of motions opens up a next level of control and responsiveness to light-driven nanoscopic motors.

Supramolecular J- and H-aggregation of Napthalimide-conjugated Dipeptide in Mixed-solvent Systems and Its Application in Cell Imaging.

In this work, a core substituted NMI-conjugated dipeptide (4MNLV) was extensively studied in mixed solvent systems to explore the polarity effect on the self-assembly pattern and their photophysical property. 4MNLV adopted a J- or H- type aggregation pattern depending upon the polarity index of the solvent system chosen. The self-assembly process was achieved through the anti-solvent effect. UV-vis study suggested that if the stock solution of 4MNLV was diluted with a relatively more polar solvent (compared to the stock solvent), then the system acquired J- type of aggregation pattern by showing a red-shift in their absorption maxima (λmax). Conversely, when the stock was diluted by a relatively less polar solvent, H-type of aggregation was observed where blue shift of λmax was noticed. The emission spectra and the lifetime of the self-assembled materials were also influenced by the chosen solvent system. The chirotopic behaviour of these self-assembled materials was studied through CD spectroscopy. Morphological study indicated the formation of helical nanofibrillar structures. The bright green fluorescence of these highly biocompatible naphthalimide-peptide conjugate was used for cell imaging application, indicating its futuristic scope.

Metal-Free Switchable Chemo- and Regioselective Alkylation of Oxindoles Using Secondary Alcohols.

In this study, we have disclosed N-alkylation and C-alkylation reactions of 2-oxindoles with secondary alcohols. Interestingly, these chemoselective reactions are tunable by changing the reaction conditions. Utilization of protic solvent and Brønsted acid catalyst afforded C-alkylation, whereas, aprotic solvent and Lewis acid catalyst afforded N-alkylation of 2-oxindoles in good to excellent yields. Regioselectivity is achieved by protecting the N-center of the oxindole and C5 alkylated product is furnished exclusively. This protocol is notable because it demonstrates functionalization at the C7 position of oxindole without the need for any directing group at the N-center. Further, a new protocol has been reported for C-H oxygenation at the benzylic position of one of the C5 alkylated derivative.

Emissive Guanosine Analog Applicable for Real-Time Live Cell Imaging.

A new emissive guanosine analog CF3thG, constructed by a single trifluoromethylation step from the previously reported thG, displays red-shifted absorption and emission spectra compared to its precursor. The impact of solvent type and polarity on the photophysical properties of CF3thG suggests that the electronic effects of the trifluoromethyl group dominate its behavior and demonstrates its susceptibility to microenvironmental polarity changes. In vitro transcription initiations using T7 RNA polymerase, initiated with CF3thG, result in highly emissive 5'-labeled RNA transcripts, demonstrating the tolerance of the enzyme toward the analog. Viability assays with HEK293T cells displayed no detrimental effects at tested concentrations, indicating the safety of the analog for cellular applications. Live cell imaging of the free emissive guanosine analog using confocal microscopy was facilitated by its red-shifted absorption and emission and adequate brightness. Real-time live cell imaging demonstrated the release of the guanosine analog from HEK293T cells at concentration-gradient conditions, which was suppressed by the addition of guanosine.

Distance-Independent Efficiency of Triplet Energy Transfer from π-Conjugated Organic Ligands to Lanthanide-Doped Nanoparticles.

Lanthanide-doped nanoparticles (LnNPs) possess unique optical properties and are employed in various optoelectronic and bioimaging applications. One fundamental limitation of LnNPs is their low absorption cross-section. This hurdle can be overcome through surface modification with organic chromophores with large absorption cross-sections. Controlling energy transfer from organic molecules to LnNPs is crucial for creating optically bright systems, yet the mechanisms are not well understood. Using pump-probe spectroscopy, we follow singlet energy transfer (SET) and triplet energy transfer (TET) in systems comprising different length 9,10-bis(phenylethynyl)anthracene (BPEA) derivatives coordinated onto ytterbium and neodymium-doped nanoparticles. Photoexcitation of the ligands forms singlet excitons, some of which convert to triplet excitons via intersystem crossing when coordinated to the LnNPs. The triplet generation rate and yield are strongly distance-dependent. Following their generation, TET occurs from the ligands to the LnNPs, exhibiting an exponential distance dependence, independent of solvent polarity, suggesting a concerted Dexter-type process with a damping coefficient of 0.60 Å-1. Nevertheless, TET occurs with near-unity efficiency for all BPEA derivatives due to the lack of other triplet deactivation pathways and long intrinsic triplet lifetimes. Thus, we find that close coupling is primarily important to ensure efficient triplet generation rather than efficient TET. Although SET is faster, we find its efficiency to be lower and more strongly distance-dependent than the TET efficiency. Our results present the first direct distance-dependent energy transfer measurements in LnNP@organic nanohybrids and establish the advantage of using the triplet manifold to achieve the most efficient energy transfer and best sensitization of LnNPs with π-conjugated ligands.

Solvent effect on the excited state photophysics of Imiquimod: A DFT/TD-DFT and spectroscopic study

Solvation plays an important role in chemistry and biology. The role of the solvent is crucial in any chemical processes such as tautomerization that controls the structure and function of biomolecules. The current study aims to explore how different solvent medium affects the tautomeric forms of an antitumor drug, Imiquimod (IMQ). We have used several spectroscopical methods, including UV–Vis absorption spectroscopy, steady-state and time-resolved fluorescence spectroscopy, and quantum mechanical (QM) calculations. Our results revealed that solvent, indeed, plays a significant role in the modulation of the photophysics of the drug. IMQ has three emission bands in protic and aprotic solvents and two bands in non-polar medium associated with different forms of the drug. Using time-resolved technique, and comparing with the predicted lifetimes from QM calculations, we succeed to assign these three forms as cation, tautomer and neutral of IMQ with 1.6 ns, 2.0 ns and 4.0 ns lifetime values, respectively. Since IMQ is a nucleobase analogue and one of the most effective medications for skin tumors; these findings about which specie of IMQ is present in a given medium, and beyond, how the medium alters the photophysics of the molecule may provide deeper insights into its structure and function.

Elucidation of the solution structure of macrocyclic paritaprevir and exploration of its antitumor potential through molecular docking

Macrocyclic molecules have emerged as significant contenders in drug development and supramolecular chemistry. Paritaprevir is a 15-membered macrocycle approved for the treatment of chronic Hepatitis C virus infection. The structural flexibility inherent in paritaprevir enables the presentation of diverse conformational features in solutions, thereby influencing its binding pattern with proteins. In this paper, we investigated the structural characteristics of paritaprevir in protic solvents (methanol and trifluoroethanol) as well as an aprotic solvent (acetonitrile) by using experimental electronic circular dichroism spectra combined with density functional theory calculations. Our study reveals that paritaprevir can adopt different molecular conformations due to its flexible carbon chain and the solvent environment. Conformer B is particularly stable in polar solvents because of the planar hydrophobic interactions between the phenanthridine and methylpyrazine groups. Density functional theory calculations-assisted structural analyses further disclosed the weak noncovalent interactions within the stable conformations of paritaprevir. Molecular docking of paritaprevir on different cancer proteins showed that the macrocycle was highly selective against lymphoma, endometrial carcinoma, colorectal cancer, and breast cancer. This suggests that paritaprevir could potentially serve as a promising lead compound for drug design targeting these specific types of cancers. The comparison between the low energy conformation and pharmacophore conformation (docking conformation) indicates that conformer B is the primary pharmacophore conformation of paritaprevir, providing important macrocyclic structural characteristics for future macrocyclic drug development.

Photoinduced π-Bond breakage causing dynamic closing-opening shell transition of Z-type Diphenylmaleonitriles molecules

Organic molecules with dynamic covalent-bonding characteristics have attracted much attention for their important role in constructing stimulus-responsive smart materials. However, it is difficult to realize sensitive and reversible covalent bond cleavage/formation through external stimuli in the aggregated state of molecules. Herein, a series of 2,3-diphenylmaleonitriles (DPMNs) with photoinduced π-bond cleavage properties have been designed and synthesized to construct the dynamic covalent bond materials. The cis-form 2,3-diphenylmaleonitriles (Z-DPMNs) exhibit significant photochromism in both solid and solution states under ultraviolet light and visible light. The photochromism stems from the photoinduced π-bond splitting of Z-DPMNs, resulting in a transition from the closed-shell to open-shell structure. Moreover, the twisted structure and molecular stacking of Z-DPMNs, the push-pull electron effect of substituents, and the external factors including temperature and solvent polarity have important effects on the dynamic conversion of π-bonds. Based on the sensitive and reversible optical performance transformation, Z-DPMNs can be applied as safety ink in anti-counterfeiting, information encryption and storage systems. This work not only provides an approach for constructing dynamic covalent bonds but also greatly enriches stimulus-responsive materials.

Theoretical insights from computational analyses: solvent-polarity-associated excited state behaviours for the novel NP-BSD chemosensor

Given the potential luminous advantages of salicylideneaniline (SA) derivatives, in this work, the phenyl π-extension-bis(salicylidene)-1,5-diaminonaphthalene (NP-BSD) fluorophore is explored on its photo-induced reactional behaviours in solvents theoretically. Given solvent surroundings with different polarities, we studied the hydrogen-bonding interactions in different solvents and their influences on excited state proton transfer (ESPT) reaction by photoexcitation for NP-BSD fluorophore. First, photo-induced geometrical variations related to dual hydrogen bonds (O1-H2···N3 and O4-H5···N6) and infrared (IR) vibrational changes and qualitative chemical bond strength reveal excited-state hydrogen bonding enhancement. Probing into the photo-induced excitation process, the charge redistribution derived from vertical excitation confirms the tendency of ESIPT reaction for NP-BSD fluorophore. By constructing potential energy surfaces (PESs) in three aprotic polar solvents, the excited-state intramolecular double proton transfer (ESIDPT) mechanism of NP-BSD could be verified that could be regulated by solvent polarity. We clarify and present the solvent-polarity-associated ESIDPT behaviours for NP-BSD fluorophore.

Highly Stable CsPbBr3@MoS2 Nanostructures: Synthesis and Optoelectronic Properties Toward Implementation into Solar Cells.

Halide perovskites (HPs) have gained significant interest in the scientific and technological sectors due to their unique optical, catalytic, and electrical characteristics. However, the HPs are prone to decomposition when exposed to air, oxygen, or heat. The instability of HP materials limits their commercialization, prompting significant efforts to address and overcome these limitations. Transition metal dichalcogenides, such as MoS2, are chemically stable and are suitable for electronic, optical, and catalytic applications. Moreover, it can be used as a protective media or shell for other nanoparticles. In this study, a novel CsPbBr3@MoS2 core-shell nanostructure (CS-NS) is successfully synthesized by enveloping CsPbBr3 within a MoS2 shell for the first time. Significant stability of CS-NSs dispersed in polar solvents for extended periods is also demonstrated. Remarkably, the hybrid CS-NS exhibits an absorption of MoS2 and quenching of the HP's photoluminescence, implying potential charge or energy transfer from HPs to MoS2. Using finite difference time domain simulations, it is found that the CS-NSs can be utilized to produce efficient solar cells. The addition of a MoS2 shell enhances the performance of CS-NS-based solar cells by 220% compared to their CsPbBr3 counterparts. The innovative CS-NS represents important progress in harnessing HPs for photovoltaic and optoelectronic applications.

Solvent and media effects on the photophysics of cranad-2 and cranad-58

Alzheimer’s disease (AD) represents the most widespread form of age-related cognitive degeneration, characterized by long-term degenerative damage, cognitive dysfunction, and profound deficits in logical thinking, knowledge acquisition, and interpersonal communication. A principal biomarker of AD involves the emergence and aggregation of β-amyloid (Aβ) plaques. Cranad derivatives are fluorescent probes capable of detecting, quantifying, and imaging Aβ. In this work, the effect of solvent and microheterogeneous environments on the photophysical behavior of CRANAD-2 and CRANAD-58 was investigated employing a large solvent set and several microorganized systems. Both the absorption and fluorescence spectra exhibit a substantial solvatochromic effect, resulting in significant Stokes shifts. Application of linear solvation energy relationships to correlate the fluorescence spectra maxima and the Stokes shift with microscopic solvent parameters suggests significant intramolecular charge transfer during the excitation, as corroborated by the increased dipole moment in the excited state. Generally, fluorescence quantum yields determined for CRANAD-2 exceed those of CRANAD-58 in most solvents, with low values in polar solvents and bigger values in non-polar solvents. Introduction of CRANAD-2 and CRANAD-58 into micellar and vesicular solutions notably augments the fluorescence emission intensity, accompanied by a blue shift in the fluorescence maxima. The fluorescence maxima values observed within microheterogeneous systems closely parallel those reported for interactions between CRANAD derivatives and soluble or aggregated Aβ amyloids which potentially constrains the efficacy of “in vivo” Aβ detection trials, because localization of CRANAD derivatives in non-polar microenvironments present in biological media could interfere with the detection of amyloid fibers.

Solvation Forces Near Hydrophobic Surfaces: A Classical Density Functional Theory Study.

We use classical density functional theory (DFT) to model solvation interactions between hydrophobic surfaces, which we show to be characterized by depletion attraction at small surface to surface separations and a slowly decaying bipower law interaction at large separations. The solvation interaction originates from van der Waals (vdW) and Coulombic interactions between molecules in the polar solvent, e.g., water, and from the molecules thermal motion and finite volume. We investigate model hydrophobic surfaces represented by bubbles and nonpolar solids, e.g., aliphatic particles, and calculate in a DFT fashion the distribution of molecules in the interlaying solvent between two such surfaces and the hydrophobic excess force resulting from it. The interactions are largely attractive, which is well-known in measurement, albeit vdW attraction between molecules in solids and in the solvent may cause repulsion at certain interface to interface separations. We commence our analysis by suggesting an asymptotic analytical bipower law expression for the solvation interaction at large separations. Thereafter we present a full numerical solution, which is in good agreement with the analytical prediction and further explores the interaction at small surface to surface separations. Our theoretical results yield adhesion energies which agree with previous experiments.

Air-Processed Perovskite Solar Cells with >25% Efficiency and High Stability Enabled by Crystallization Modulation and Holistic Passivation.

Organic semiconductors (e.g., PCBM and IDIC) frequently serve as interface passivants for perovskite solar cells (PSCs) due to their beneficial passivation effects on perovskite interfaces. However, their passivation to the interiors of perovskite films is greatly limited by their poor solubility in polar solvents and compatibility issues. Here the facile synthesis of organic semiconductor nanoparticle (NP) passivants that readily disperse in perovskite inks is reported. Adding these NPs into perovskite inks not only modulates perovskite crystallization, improves film quality and conductivity, but also achieves holistic bulk film passivation. Consequently, blade-coated p-i-n PSCs with ICBA NPs achieve an impressive efficiency of 25.1% (independently certified as 25.0%), the highest reported value for air-processed PSCs irrespective of fabrication methods or device structures. This work develops a novel approach for effective and holistic perovskite passivation by converting conventional passivants to perovskite-compatible NPs, paving the way for more efficient and stable perovskite solar devices.

A Comprehensive Study of Factors Affecting the Prediction of the pKa Shift of Asp26 in Thioredoxin Protein.

The stable protonation state of ionizable amino acids in a protein can be predicted by computing the pKa shift of that residue within the protein environment. Thermodynamic Integration (TI) is an ideal molecular dynamics-based approach for predicting the pKa shift of ionizable protein residues. Here, we probe TI-based simulation protocols for their ability to accurately predict the pKa shift of Asp26 in thioredoxin. While implicit solvent models can predict the pKa shift accurately, explicit solvent models result in substantial errors. To understand the underlying reason for this surprising discrepancy, we investigate the role of various factors such as solvent models, conformational sampling, background charges, and polarization.

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.

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

AbstractThe 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.