Structural stability of DNA origami nanostructures in organic solvents.

DNA origami nanostructures have attracted significant attention as an innovative tool in a variety of research areas, spanning from nanophotonics to bottom-up nanofabrication. However, the use of DNA origami is often restricted by their rather limited structural stability in application-specific conditions. The structural integrity of DNA origami is known to be superstructure-dependent, and the integrity is influenced by various external factors, for example cation concentration, temperature, and presence of nucleases. Given the necessity to functionalize DNA origami also with non-water-soluble entities, it is important to acquire knowledge of the structural stability of DNA origami in various organic solvents. Therefore, we herein systematically investigate the post-folding DNA origami stability in a variety of polar, water-miscible solvents, including acetone, ethanol, DMF, and DMSO. Our results suggest that the structural integrity of DNA origami in organic solvents is both superstructure-dependent and dependent on the properties of the organic solvent. In addition, DNA origami are generally more resistant to added organic solvents in folding buffer compared to that in deionized water. DNA origami stability can be maintained in up to 25-40% DMF or DMSO and up to 70-90% acetone or ethanol, with the highest overall stability observed in acetone. By rationally selecting both the DNA origami design and the solvent, the DNA origami stability can be maintained in high concentrations of organic solvents, which paves the way for more extensive use of non-water-soluble compounds for DNA origami functionalization and complexation.

Exploring the solubility and intermolecular interactions of biologically significant amino acids l-serine and L-cysteine in binary mixtures of H2O + DMF, H2O + DMSO and H2O + ACN in temperature range from T = 288.15 K to 308.15 K.

In the presented work, a study on the solubility and intermolecular interactions of l-serine and L-cysteine was carried out in binary mixtures of H2O + dimethylformamide (DMF), H2O + dimethylsulfoxide (DMSO), and H2O + acetonitrile (ACN) in the temperature range of T = 288.15 K to 308.15 K. l-serine exhibited the highest solubility in water, while L-cysteine was more soluble in water-DMF. The solvation process was assessed through standard Gibbs energy calculations, indicating the solvation stability order: water-ACN > water-DMSO > water-DMF for l-serine, and water-DMF > water-DMSO > water-ACN for L-cysteine. This study also explored the influence of these amino acids on solvent-solvent interactions, revealing changes in chemical entropies and self-association patterns within the binary solvent mixtures.

Gas chromatography mass spectrometer determination of dimethylamine impurity in N,N-dimethylformamide solvent by derivatization of N,N-dimethylbenzamide with benzoyl chloride agent.

This study describes the development of a reliable and linear analytical method for precisely determining dimethylamine impurity in N,N-dimethylformamide solvent utilizing a benzoyl chloride derivatization reagent and a gas chromatography mass spectrometer. Benzoyl chloride was used to derivatize dimethylamine. At normal temperature, benzoyl chloride combined with dimethylamine, producing N,N-dimethylbenzamide. This method separated N,N-dimethylbenzamide using Rtx-5 amine (30 m × 0.32 mm × 1.50 µm) as the stationary phase, helium as the carrier gas, argon as the collision gas, and methanol as the diluent. The column flow rate was 2 mL/min. The retention time of N,N-dimethylbenzamide was determined to be 8.5 min. Precision, linearity, and accuracy were tested using ICH Q2 (R2) and USP<1225> guidelines. The percentage coefficient of variation (CV) for N,N-dimethylbenzamide in the system suitability parameter was 1.1%. The correlation coefficient of N,N-dimethylbenzamide was found to be >0.99. In the method precision parameter, the % CV for N,N-dimethylbenzamide was found to be 1.9%, whereas the % CV for N,N-dimethylbenzamide was 1.2% in intermediate precision. The percentage recovery of N,N-dimethylbenzamide was determined to be between 80% and 98%.

PVP/aprepitant microcapsules produced by supercritical antisolvent process.

The supercritical antisolvent (SAS) process was a green alternative to improve the low bioavailability of insoluble drugs. However, it is difficult for SAS process to industrialize with limited production capacity. A coaxial annular nozzle was used to prepare the microcapsules of aprepitant (APR) and polyvinylpyrrolidone (PVP) by SAS with N, N-Dimethylformamide (DMF) as solvent. Meanwhile, the effects of polymer/drug ratio, operating pressure, operating temperature and overall concentration on particles morphology, mean particle diameter and size distribution were analyzed. Microcapsules with mean diameters ranging from 2.04 µm and 9.84 µm were successfully produced. The morphology, particle size, thermal behavior, crystallinity, drug content, drug dissolution and residual amount of DMF of samples were analyzed. The results revealed that the APR drug dissolution of the microcapsules by SAS process was faster than the unprocessed APR. Furthermore, the drug powder collected every hour is in the kilogram level, verifying the possibility to scale up the production of pharmaceuticals employing the SAS process from an industrial point of view.

Anion-Binding Properties of Short Linear Homopeptides.

A comprehensive thermodynamic and structural study of the complexation affinities of tetra (L1), penta (L2), and hexaphenylalanine (L3) linear peptides towards several inorganic anions in acetonitrile (MeCN) and N,N-dimethylformamide (DMF) was carried out. The influence of the chain length on the complexation thermodynamics and structural changes upon anion binding are particularly addressed here. The complexation processes were characterized by means of spectrofluorimetric, 1H NMR, microcalorimetric, and circular dichroism spectroscopy titrations. The results indicate that all three peptides formed complexes of 1:1 stoichiometry with chloride, bromide, hydrogen sulfate, dihydrogen phosphate (DHP), and nitrate anions in acetonitrile and DMF. In the case of hydrogen sulfate and DHP, anion complexes of higher stoichiometries were observed as well, namely those with 1:2 and 2:1 (peptide:anion) complexes. Anion-induced peptide backbone structural changes were studied by molecular dynamic simulations. The anions interacted with backbone amide protons and one of the N-terminal amine protons through hydrogen bonding. Due to the anion binding, the main chain of the studied peptides changed its conformation from elongated to quasi-cyclic in all 1:1 complexes. The accomplishment of such a conformation is especially important for cyclopeptide synthesis in the head-to-tail macrocyclization step, since it is most suitable for ring closure. In addition, the studied peptides can act as versatile ionophores, facilitating transmembrane anion transport.

Optimization of peptide synthesis time and sustainability using novel eco-friendly binary solvent systems with induction heating on an automated peptide synthesizer.

On December 12th, 2023, the European Commission took regulatory action to amend Annex XVII of REACH, imposing restrictions on the use of N,N-dimethylformamide (DMF) within the EU market owing to its high toxicity. Historically, DMF has been widely considered the gold standard for solid-phase peptide synthesis (SPPS). Being urgent to propose alternative solvents, we tested the suitability of non-hazardous neat and mixed solvents. Notably, binary solvent mixtures containing dimethyl sulfoxide as one of the solvent partners demonstrated high efficacy in solubilizing reagents while maintaining the desired swelling characteristics of common resins. A series of binary solvent mixtures were tested in automated SPPS, both at room temperature and high temperature, employing the PurePep® Chorus synthesizer, which enabled controlled induction heating between 25 and 90°C with oscillation mixing. The performances were assessed in challenging peptide sequences, i.e., ACP (65-74), and in longer and aggregating sequences like SARS-CoV-2 RBM (436-507) and ß-amyloid (1-42). Furthermore, as part of the proposed sustainable approach to minimize the utilization of hazardous solvents, we coupled the novel PurePep EasyClean catch-and-release purification technology. This work, addressing regulatory compliance, emphasizes the crucial role of green chemistry in advancing safer and more environmentally friendly practices in SPPS.

Dimethylformamide dimethyl acetal reagent for in situ chiral analyses of organic molecules on Titan with the Dragonfly mass spectrometer space instrument (Dragonfly mission).

Thanks to the Cassini-Huygens space mission between 2004 and 2017, a lot was learned about Titan, the biggest satellite of Saturn, and its intriguing atmosphere, surface, and organic chemistry complexity. However, key questions about the potential for the atmosphere and surface chemistry to produce organic molecules of direct interest for prebiotic chemistry and life did not find an answer. Due to Titan potential as a habitable world, NASA selected the Dragonfly space mission to be launched in 2027 to Titan's surface and explore the Shangri-La surface region for minimum 3 years. One of the main goals of this mission will be to understand the past and actual abundant prebiotic chemistry on Titan, especially using the Dragonfly Mass Spectrometer (DraMS). Two recently used sample pre-treatments for Gas Chromatography - Mass Spectrometry (GC-MS mode of DraMS) analyses are planned prior analysis to extract refractory organic molecules of interest for prebiotic chemistry and astrobiology. The dimethylformamide dimethylacetal (DMF-DMA) derivatization reaction offers undoubtedly an opportunity to detect biosignatures by volatilizing refractory biological or prebiotic molecules and conserving the chiral carbons' conformation while an enantiomeric excess indicates a chemical feature induced primarily by life (and may be aided on the primitive systems by light polarization). The goal of this study is to investigate the ageing of DMF-DMA in DraMS (and likely MOMA) capsules prior to in situ analysis on Titan (or Mars). The main results highlighted by our work on DMF-DMA are first its satisfactory stability for space requirements through time (no significant degradation over a year of storage and less than 30 % of lost under thermal stress) to a wide range of temperature (0 °C to 250 °C), or the presence of water and oxidants during the derivatization reaction (between 0 and 10 % of DMF-DMA degradation). Moreover, this reagent derivatized very well amines and carboxylic acids in high or trace amounts (ppt to hundreds of ppm), conserving their molecular conformation during the heat at 145 °C for 3 min (0 to 4% in the enantiomeric form change).

Core-Shell Double Gyroids Directed by Selective Solvation for ABC Triblock Terpolymers.

The formation of ABC triblock terpolymers through solution casting is still challenging. In this study, core-shell double gyroid network structures are fabricated via solution casting using poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) (F)-b-[poly(4-vinylpyridine) (P4VP) (P)]-b-[polystyrene (PS) (S)] (FPS) triblock terpolymers in N,N-dimethylformamide (DMF). Upon heat treatment, the polymer tends to form a sphere-in-lamellar structure at the F/S interface. Given the solubility properties of each component in DMF, it is anticipated that the effective volume fraction of F relative to P would increase in concentrated solutions and the effective volume fraction of S would decrease. The microphase-separated structure derived from the DMF solution consistently results in the formation of a network structure composed of a core-shell double gyroid, with F as the matrix, P as the shell, and S as the core, and their periodic lengths gradually increase to 110.8, 131.8, and 162.7 nm as increase molecular weights of PS blocks to 13.8, 20.7, and 28.8 kg mol-1. Based on the solubility properties of the polymer components highlighted in this study, the solvent selection strategy is broadly applicable to ABC triblock terpolymers featuring various polymer components, offering a more efficient avenue for fabricating core-shell double gyroid structures.

N,N-Dimethyl Formamide European Restriction Demands Solvent Substitution in Research and Development.

As of December 2023, the use of common solvent N,N-dimethyl formamide (DMF) will be restricted in the European Union because of its reproductive health hazard. Industrial facilities must comply with stricter exposure limits, and researchers are recommended to find alternative solvents. Here we explain the restrictions on DMF, which disciplines are affected, and how to substitute DMF to keep research and development commercially relevant.

Determination of water content in dimethyl sulfoxide/N,N-dimethyl formamide and methanol content in ethanol by solvatochromism of azo dye, 2-(tert-butyl)-4-methoxy-6-(naphthalen-1-yldiazenyl) phenol.

A novel 2-(tert-butyl)-4-methoxy-6-(naphthalen-1-yldiazenyl)phenol (NAP) was synthesized by coupling reaction of 2-tert-butyl-4-methoxyphenol with diazotized naphthylamine as diazo component. The azo dye was characterized by NMR, FT-IR and UV-vis spectroscopic techniques. The visible spectrum of NAP was recorded in different solvents and at different pHs. NAP exhibited a large wavelength shift with increasing solvent polarity, showing significant color change over a wide range in different solvents. The determination of water content in organic solvents miscible with water such as dimethyl sulfoxide (DMSO)/N,N-dimethyl formamide (DMF) and methanol content in ethanol, which is also a common mixture were investigated with NAP which is azo dye. The present reported solvatochromic compound for the determination of water content in DMSO/DMF and methanol content in ethanol showed a fairly wide linear range compared to some previously reported solvatochromic compounds in the literature. In addition, the solvatochromism of NAP allows the determination of methanol content in ethanol, which has caused many deaths, with a fast, cheap and easy method.

Room-Temperature Dialkylamination of Chloroheteroarenes Using a Cu(II)/PTABS Catalytic System.

The dimethylamino functionality has significant importance in industrially relevant molecules and methodologies to install these efficiently are highly desirable. We report herein a highly efficient, room-temperature dimethylamination of chloroheteroarenes performed via the in-situ generation of dimethylamine using N,N-dimethylformamide (DMF) as precursor wiith a large substrate scope that includes various heteroarenes, purines as well as commercially relevant drugs such as altretamine, ampyzine and puromycin precursor.

Crystallization Pathways of FABr-PbBr2-DMF and FABr-PbBr2-DMSO Systems: The Comprehensive Picture of Formamidinium-Based Low-Dimensional Perovskite-Related Phases and Intermediate Solvates.

In this study, we systematically investigated the phase diversity and crystallization pathways of the FABr excessive regions of two ternary systems of FABr-PbBr2-DMF and FABr-PbBr2-DMSO (where FA+-formamidinium cations, DMF-dimethylformamide and DMSO-dimethyl sulfoxide solvents). In these systems, a new FA3PbBr5 phase with a structure containing chains of vertex-connected PbBr6 octahedra is discovered, and its crystal structure is refined. We experimentally assess fundamental information on differences in the mechanisms of crystallization process in FABr-PbBr2-DMF and FABr-PbBr2-DMSO systems and determine possible pathways of crystallization of hybrid perovskites. We show that intermediate solvate phases are not observed in the system with DMF solvent, while a number of crystalline solvates tend to form in the system with DMSO at various amounts of FABr excess.

Distinct Hydrogen Bonding Dynamics Underlies the Microheterogeneity in DMF-Water Mixtures.

The hydrogen bonding interaction between the amide functional group and water is fundamental to understanding the liquid-liquid heterogeneity in biological systems. Herein, the structure and dynamics of the N,N-dimethylformamide (DMF)-water mixtures have been investigated by linear and nonlinear IR spectroscopies, using the hydroxyl stretch and extrinsic probe of thiocyanate as local vibrational reporters. According to vibrational relaxation dynamics measurements, the orientational dynamics of water is not directly tied to those of DMF molecules. Wobbling-in-a-cone analysis demonstrates that the water molecules have varying degrees of angular restriction depending on their composition due to the formation of specific water-DMF networks. Because of the preferential solvation by DMF molecules, the rotational dynamics of the extrinsic probe is slowed significantly, and its rotational time constants are correlated to the change of solution viscosity. The unique structural dynamics observed in the DMF-water mixtures is expected to provide important insights into the underlying mechanism of microscopic heterogeneity in binary mixtures.

Local Structure of DMF-Water Mixtures, as Seen from Computer Simulations and Voronoi Analysis.

Molecular dynamics simulations of mixtures of N,N-dimethylformamide (DMF) with water of various compositions, covering the entire composition range, are performed on the canonical (N,V,T) ensemble. The local structure of the mixtures is analyzed in terms of radial distribution functions and the contributions of the first five neighbors to them, various order parameters of the water molecules around each other, and properties of the Voronoi polyhedra of the molecules. The analyses lead to the following main conclusions. The two molecules are mixing with each other even on the molecular scale; however, small self-aggregates of both components persist even at their small mole fraction values. In particular, water-water H-bonds exist in the entire composition range, while water clusters larger than 3 and 2 molecules disappear above the DMF mole fraction values of about 0.7 and 0.9, respectively. The O atoms of the DMF molecules can well replace water O atoms in the hydrogen-bonding network. Further, the H-bonding structure is enhanced by the presence of the hydrophobic CH3 groups of the DMF molecules. On the other hand, the H-bonding network of the molecules gradually breaks down upon the addition of DMF to the system due to the lack of H-donating groups of the DMF molecules. Finally, in neat DMF, the molecules form weak, CH-donated H-bonds with each other; however, these H-bonds disappear upon the addition of water due to the increasing competition with the considerably stronger OH-donated H-bonds DMF can form with the water molecules.

Overcoming GNA/RNA base-pairing limitations using isonucleotides improves the pharmacodynamic activity of ESC+ GalNAc-siRNAs.

We recently reported that RNAi-mediated off-target effects are important drivers of the hepatotoxicity observed for a subset of GalNAc-siRNA conjugates in rodents, and that these findings could be mitigated by seed-pairing destabilization using a single GNA nucleotide placed within the seed region of the guide strand. Here, we report further investigation of the unique and poorly understood GNA/RNA cross-pairing behavior to better inform GNA-containing siRNA design. A reexamination of published GNA homoduplex crystal structures, along with a novel structure containing a single (S)-GNA-A residue in duplex RNA, indicated that GNA nucleotides universally adopt a rotated nucleobase orientation within all duplex contexts. Such an orientation strongly affects GNA-C and GNA-G but not GNA-A or GNA-T pairing in GNA/RNA heteroduplexes. Transposition of the hydrogen-bond donor/acceptor pairs using the novel (S)-GNA-isocytidine and -isoguanosine nucleotides could rescue productive base-pairing with the complementary G or C ribonucleotides, respectively. GalNAc-siRNAs containing these GNA isonucleotides showed an improved in vitro activity, a similar improvement in off-target profile, and maintained in vivo activity and guide strand liver levels more consistent with the parent siRNAs than those modified with isomeric GNA-C or -G, thereby expanding our toolbox for the design of siRNAs with minimized off-target activity.

Optical Properties of Composites Based on Poly(o-phenylenediamine), Poly(vinylenefluoride) and Double-Wall Carbon Nanotubes.

In this work, synthesis and optical properties of a new composite based on poly(o-phenylenediamine) (POPD) fiber like structures, poly(vinylidene fluoride) (PVDF) spheres and double-walled carbon nanotubes (DWNTs) are reported. As increasing the PVDF weight in the mixture of the chemical polymerization reaction of o-phenylenediamine, the presence of the PVDF spheres onto the POPD fibers surface is highlighted by scanning electron microscopy (SEM). The down-shift of the Raman line from 1421 cm-1 to 1415 cm-1 proves the covalent functionalization of DWNTs with the POPD-PVDF blends. The changes in the absorbance of the IR bands peaked around 840, 881, 1240 and 1402 cm-1 indicate hindrance steric effects induced of DWNTs to the POPD fiber like structures and the PVDF spheres, as a consequence of the functionalization process of carbon nanotubes with macromolecular compounds. The presence of the PVDF spheres onto the POPD fiber like structures surface induces a POPD photoluminescence (PL) quenching process. An additional PL quenching process of the POPD-PVDF blends is reported to be induced in the presence of DWNTs. The studies of anisotropic PL highlight a change of the angle of the binding of the PVDF spheres onto the POPD fiber like structures surface from 50.2° to 38° when the carbon nanotubes concentration increases in the POPD-PVDF/DWNTs composites mass up to 2 wt.%.

The shrinking behavior, mechanism and anti-shrinkage resolution of an electrospun PLGA membrane.

The deformation shrinkage of a poly(lactide-co-glycolide) (PLGA) fibrous material seriously affects its biomedical application. To demonstrate the underlying shrinking mechanism and to find a method to prevent the shrinkage of an electrospun PLGA membrane, we investigated the shrinking behavior of PLGA electrospun membranes under various test conditions and discussed the underlying shrinking mechanism. The results indicated that the shrinkage of the electrospun PLGA membrane was mainly regulated by the glass transition of its polymer fiber; the temperature and liquid environment were found to be the two main factors leading to the shrinkage of the electrospun PLGA membrane through affecting its glass transition. Then a heat stretching (HS) technique was proposed by us to stabilize the electrospun PLGA membrane. After HS treatment, the glass transition temperature (Tg) of the electrospun PLGA membrane could increase from 48.38 °C to 54.55 °C. Our results indicated that the HS-treated membranes could maintain a high area percentage of 90.89 ± 2.27% and 84.78 ± 3.36% after immersion respectively in PBS and blood at 37 °C for 2 hours. Further experiments confirmed that the HS technique could also stabilize the dimensional structure of the electrospun PDLLA membrane in PBS and blood at 37 °C. This study provides an effective strategy for preventing the shrinkage of electrospun polyester biomaterials in a physiological environment that may benefit both the material structural stability and the in vivo biological performance.

Temperature and solvent exposure response of three fatty acid peroxygenase enzymes for application in industrial enzyme processes.

Free fatty acids (FFAs) are a useful feedstock for a range of industrial chemical synthesis applications. However, efficiently converting FFAs to molecules for biofuel and other high-value chemicals requires more efficient and cost-effective catalysts. Cytochrome P450 fatty acid peroxygenases (CYP152) have a unique chemistry that allows use of the peroxide shunt pathway for biochemical conversion of FFAs. Known CYP152s are heat labile, however, requiring characterization of more thermotolerant versions for use in industrial applications. A fatty acid peroxygenase from Bacillus methanolicus (CYP152K6) was shown here to have a higher optimal reaction temperature than OleT (CYP152L1). CYP152K6 was stable up to 50 °C and showed great stability in 3% acetone and dimethylformamide. Stability in solvents helps the enzyme's substrates remain soluble in solution for more efficient catalysis, and heat stability allows enzymes to remain active longer during industrial processes.

Effect of solvent type on the dispersion quality of spray-and freeze-dried CNCs in PLA through rheological analysis.

Polylactide (PLA) nanocomposites with spray-and freeze-dried cellulose nanocrystals (i.e., SCNC and FCNC) were prepared through solution casting using four different solvents: tetrahydrofuran (THF), chloroform (CHL), dimethylformamide (DMF), and dimethyl sulfoxide (DMSO). Small amplitude oscillatory shear rheological analysis was extensively employed to explore the CNC dispersion quality in PLA. Overall, the rheological properties differences of PLA/SCNC and PLA/FCNC nanocomposites were not very significant. Moreover, the use of THF and CHL did not lead to a proper dispersion of CNCs in PLA due to their low dielectric constants. On the other hand, while the use of DMF was effective on the enhancement of CNC dispersion, DMSO could more dramatically lead to such enhancement due to its higher dielectric constant. The percolation threshold in PLA/SCNC nanocomposites prepared with DMF and DMSO was predicted around 1.52 and 0.12 wt% CNC, respectively. The crystallization behavior of PLA/nanocomposites prepared with DMF and DMSO were also explored.

Electrospun lignin-PVP nanofibers and their ability for structuring oil.

This work explores the electrospinnability of low-sulfonate Kraft lignin (LSL)/polyvinylpyrrolidone (PVP) solutions in N,N-dimethylformamide (DMF) and the ability of the different micro- and nano-architectures generated to structure castor oil. LSL/PVP solutions were prepared at different concentrations (8-15 wt%) and LSL:PVP ratios (90:10-0:100) and physico-chemically and rheologically characterized. The morphology of electrospun nanostructures mainly depends on the rheological properties of the solution. Electrosprayed nanoparticles or micro-sized particles connected by thin filaments were obtained from solutions with low LSL/PVP concentrations and/or high LSL:PVP ratios, whereas beaded or bead-free nanofibers were produced by increasing concentration and/or decreasing LSL:PVP ratio, due to enhanced extensional viscoelastic properties and non-Newtonian characteristics. Electrospun LSL/PVP nanofibers are able to form oleogels by simply dispersing them into castor oil at concentrations between 10 and 30 wt%. The rheological properties of the oleogels may be tailored by modifying the LSL:PVP ratio and nanofibers content. The potential application of these oleogels as bio-based lubricants was also explored in a tribological cell. Satisfactory friction and wear results are achieved when using oleogels structured by nanofibers mats with enhanced gel-like properties as lubricants. Overall, electrospinning of lignin/PVP solutions can be proposed as a simple and effective method to produce nanofibers for oil structuring.