This article describes the use of dimethyl-aniline-alkyl halide charge transfer complexes as a linchpin for sunlight-initiated C-C bond formation with activated methylene compounds, including malonates, malononitriles, and 2-cyano-esters. DFT calculations shed light on charge transfer complex formation and structure as well as on the mechanism.

Self-healing through dynamic noncovalent bonds in polymeric materials offers the possibility to regain mechanical integrity and mechanical properties, such as elasticity and surface adhesion, upon damage inflicted on the material. It is therefore of great interest in any field where products are expected to have a long service life. For the design of a new class of self-healing energetic polymeric materials, highly energetic vinyl imidazolium perchlorate units were derivatized with diethylene glycol monomethyl ether side groups, with the imidazolium – ethylene glycol groups serving as reversible non-covalent crosslinkers. The interleaved self-healing polymer networks are obtained by bulk photopolymerization of the vinyl imidazolium perchlorate ionic liquid monomers. The resulting polymer, poly 1-[2-[2-(2-methoxyethoxy)ethoxy]ethyl]-3-vinyl-imidazolium perchlorate exhibits long-sought intrinsic self-healing properties, as well as the crucial ability to re-bond to the surface of microcrystalline ammonium perchlorate oxidizer, rendering it an interesting candidate as a fuel-binder in propellant compositions. The role of absorbed water molecules in the self-healing behavior of the polymer, as well as the ability of the polymer to regain surface wetting and adhesion to surfaces, are studied in detail.

Increasing the molecular rigidity of bioactive compounds by intramolecular hydrogen bonds (IMHB) may affect both pharmacodynamics (PD) and pharmacokinetics (PK) by an increase in molecular recognition, lipophilicity and membrane permeability. Recently, in our study on opioids lipophilicity, we suggested two types of IMHBs, i.e., O-H⋯N and N+-H…O, which may exist in 14-oxymorphinan structures and may explain some trends and even apparent anomalies in their pharmacologically relevant molecular properties. In the present study we show, both experimentally and computationally, that these IMHBs indeed exist in the three FDA-approved opioid antagonists, Naloxone, Naltrexone and Nalmefene, as well as in their 3-O- and 14-O-methylated derivatives. Since the charged form of these morphinans is the biologically active species, we propose that the charge-assisted IMHB (CAHB) N+-H…O, which is herein studied for the first time, plays an important role in the bioactivity of this subfamily of opioids.

Plastic pollution poses a significant threat to soil ecosystems, yet the role of volatile organic compounds (VOCs) in plastic degradation is not well-studied. The present research focuses on the impact of polyethylene (PE), polylactic acid (PLA), and poly(butylene-adipate-co-terephthalate) (PBAT) residues on soil in a 12-week long lab-scale aerobic experiment. The study focused on the dynamics of VOC profiles, soil physicochemical properties, and microbial communities. PBAT, known for its biodegradability, produced a distinct VOC profile with hazardous compounds such as 1,3-butadiene, which is consistently associated with cardiovascular diseases and leukemia. Microbial analysis of PBAT revealed distinct bacterial and fungal diversity responses, along with unique KEGG pathway profiles compared to PE and PLA, suggesting its biodegradation process may involve biofilm formation and quorum sensing. Correlation analysis based on the relevant abundance of specific microbes exhibited strong positive correlations, such as Streptomyces with propyne emission and Hydrogenispora with ethylene emission. These results demonstrated distinct biodegradation patterns of various plastics in soil, identified through the combination of VOC detection and microbiome analysis.

In cold methanol, energetic ionic liquid 1-n-propyl-3-vinyl-imidazol-1-ium perchlorate, 1, crystallizes in the presence of excess Ba(ClO4)2, 2, into tetrakis 1-propyl-3-vinyl-imidazol-1-ium·barium hexa-perchlorate, 3. Crystals of 3, with molecular formula (C8H13N2)4·BaCl6O24, are colorless and monoclinic, with space group P21/c. The crystal structure is characterized by a dodecahedral coordination around the barium atom, with each perchlorate chelating Ba2+ in a κ2O,O’ fashion, and the Ba(ClO4)64− anion is surrounded by four imidazolium cations.

A systematic study of trends in the lipophilicity of prominent representatives of the opioid family, including natural, semisynthetic, synthetic, and endogenous neuropeptide opioids, is described. This was enabled by a straightforward 1H NMR-based logP/D determination method developed for compounds holding at least one aromatic hydrogen atom. Moreover, the new method enables a direct simultaneous logD determination of opioid mixtures, overcoming the high sensitivity of this family to the measurement conditions, which is critical when a determination of the exact ΔlogD values of matched pairs is required. Interpretation of the experimental ΔlogD 7.4 values of selected matched pairs, focusing inter alia on the 3-OMe and 14-OMe motifs in morphinan opioids, is suggested with the aid of DFT calculations and may be useful for the discovery of new opioid therapeutics.

Fluorine atoms play an important role in all branches of chemistry and accordingly, it is very important to study their unique and varied effects systematically, in particular, the structure-physicochemical properties relationship. The present study describes exceptional physicochemical effects resulting from a H/F exchange at the methylene bridge of gem-difunctional compounds. The Delta log P(CF2-CH2) values, that is, the change in lipophilicity, observed for the CH2/CF2 replacement in various alpha,alpha-phenoxy- and thiophenoxy-esters/amides, diketones, benzodioxoles and more, fall in the range of 0.6-1.4 units, which for most cases, is far above the values expected for such a replacement. Moreover, for compounds holding more than one such gem-difunctional moiety, the effect is nearly additive, so one can switch from a hydrophilic compound to a lipophilic one in a limited number of H/F exchanges. DFT studies of some of these systems revealed that polarity, conformational preference as well as charge distributions are strongly affected by such hydrogen to fluorine atom substitution. The pronounced effects described, are a result of the interplay between changes in polarity, H-bond basicity and molecular volume, which were obtained with a very low 'cost' in terms of molecular weight or steric effects and may have a great potential for implementation in various fields of chemical sciences.

Combined molecular, physicochemical and chemical properties of electrophilic warheads can be applied to create covalent drugs with diverse facets. Here we study these properties in fluorinated diketones (FDKs) and their multicomponent equilibrium systems in the presence of protic nucleophiles, revealing the potential of the CF2(CO)2 group to act as a multifaceted warhead for reversible covalent drugs. The equilibria compositions of various FDKs in water/octanol contain up to nine species. A simultaneous direct species-specific 19F-NMR-based log P determination of these complex equilibria systems was achieved and revealed in some cases lipophilic to hydrophilic shifts, indicating possible adaptation to different environments. This was also demonstrated in 19F-MAS-NMR-based water-membrane partitioning measurements. An interpretation of the results is suggested by the aid of a DFT study and 19F-DOSY-NMR spectroscopy. In dilute solutions, a model FDK reacted with protected cysteine to form two hemi-thioketal regioisomers, indicating possible flexible regio-reactivity of CF2(CO)2 warheads toward cysteine residues.

Novel polyimine vitrimers were constructed from cyclophosphazene bearing three aldehyde groups, CP-3AP, terephthalaldehyde, TPA, and diaminodiphenyl methane, MDA. Owing to the incorporation of phosphazene skeleton and high content of aromatic ring structure, the new vitrimers exhibit superior flame retardancy with UL-94 V0 level and high limiting oxygen index, LOI, of similar to 40%, high thermostability with T-5% (5% weight loss) of similar to 420 degrees C and similar to 75% residues at 800 degrees C. Vitrimers owned high Tg of ca 146 degrees C, robust tensile strength of similar to 56 MPa and excellent reprocessability with greater than 90% recycling efficiency of mechanical properties even when subjected to three recycling cycles based on imine dynamic covalent bond. Additionally, possible bond exchange mechanisms that are involved in the processability were systematically researched by model compounds using TOF-mass spectroscopy. CP-3AP could be recovered by acidolysis with high 81% efficiency. Such excellent comprehensive properties of phosphazene based polyimine vitrimers open new mutes to a variety of high-performance vitrimers, especially in terms of thermal and flame retardancy properties.

Systematically studying the lipophilicity of phosphorus compounds is of great importance for many chemical and biological fields and particularly for medicinal chemistry. Here, we report on the study of trends in the lipophilicity of a wide set of phosphorus compounds relevant to drug design including phosphates, thiophosphates, phosphonates, thiophosphonates, bis-phosphonates, and phosphine chalcogenides. This was enabled by the development of a straightforward log P determination method for phosphorus compounds based on 31P-NMR spectroscopy. The log P values measured ranged between -3.2 and 3.6, and the trends observed were interpreted using a DFT study of the dipole moments and by H-bond basicity (pKHB) measurements of selected compounds. Clear signal separation in 31P-NMR spectroscopy grants the method high tolerability to impurities. Moreover, the wide range of chemical shifts for the phosphorus nucleus (250 to -250 ppm) enables a direct simultaneous log P determination of phosphorus compound mixtures in a single shake-flask experiment and 31P-NMR analysis.

Polymers, made of energetic ionic liquid building blocks, are used as the fuel-binder part in propellant compositions. These compositions exhibit desired mechanical and energetic properties and may serve as a photoactive feed for 3D printable propellants. Quaternary vinyl imidazolium energetic salts, having perchlorate and nitrate counter ions, are used as monomers in fuel binder polymers, while ammonium perchlorate is used as the heterogeneous oxidizer in the composition. The vinyl groups on the heterocyclic cations provide covalent interconnecting sites for the construction of the polymer backbone and binding sites for in chain plasticizers, enabling control over mechanical and initiation sensitivity properties in the cured composite product. The advantageous oxygen balance and heat of formation values of these ionic liquid monomers, along with their ability to photo polymerize, allow both the effective dispersion and reduced ratios of the heterogeneous oxidizer content without compromising the energetic properties of the resultant propellant. An intermolecular interaction between the heterocyclic imidazolium units was identified, which enables noncovalent reinforcement and may explain some of the observed properties of the compositions. Pressure independent burn rates were achieved in compositions containing 2-ethoxyethyl acrylate plasticizer, thus avoiding the need for additional additives, stratification, and geometrical constraints on the burning bulk.

We show that 1-(2-hydroxyethyl)-1H-imidazol-3-ium and 1-(2-hydroxyethyl)-3-methyl-1H-imidazol-3-ium salts, as well as the salts of their nitrite esters, that include oxidizing anions (so-called explosphores) such as nitrate, picrate and perchlorate are endowed with high enthalpies of decomposition, high decomposition temperatures, and high densities. This combined with detonation velocities and pressures calculated using Explo5, indicates that especially the perchlorate salts have potential as energetic materials. All the studied salts are easily preparable in up to gram scale through two or three synthetic steps from simple imidazole. Many of these salts are ionic liquids, which may render them useful as energetic plasticizers or gel filled materials.

Plasticulture, the practice of using plastic materials in agricultural applications, consumes about 6.7 million tons of plastics every year, which is about 2% of the overall global annual plastics production. For different reasons, plastic material used for agriculture is difficult to recycle. Therefore, most of it is either buried in fertile soils, thereby significantly causing deterioration of their properties, or, at best case, end in landfills where its half-life is measured in decades and even centuries. Hence, developing biodegradable plastic materials that are suitable for agricultural applications is a vital and inevitable need for the global human society. In our labs, two types of potentially biodegradable plastic polymer films were prepared and characterized imidazolium in terms of their bio-degradability. In the first approach, polymers made of ionic liquid monomers were prepared using photo radical induced polymerization. The second approach relies on formation of polyethylene-like n-alkane disulfide polymers from 1,ω-di-thiols through thermally activated air oxidation. These two families of materials were tested for their biodegradability in soils by using a simulation system that combines a controlled environment chamber equipped with a respirometer and a proton-transfer-reaction time of flight mass spectrometer (PTR-TOF-MS) system. This system provides a time-dependent and comprehensive fingerprint of volatiles emitted in the degradation process. The results obtained thus far indicate that whereas the ionic-liquid based polymer does not show significant bio-degradability under the test conditions, the building block monomer, 1,10-n-decane dithiol, as well as its disulfide-based polymer, are bio-degradable. The latter reaching, under basic soil conditions and in room temperature, ∼20% degradation within three months. These results suggest that by introduction of disulfide groups into the polyethylene backbone one may be able to render it biodegradable, thus considerably shortening its half-life in soils. Principal component analysis, PCA, of the data about the total volatiles produced during the degradation in soil indicates a distinctive volatile "fingerprint" of the disulfide-based bio-degradable products which comes from the volatile organic compounds portfolio as recorded by the PTR-TOF-MS. The biodegradation volatile fingerprint of this kind of film was different from the "fingerprint" of the soil background which served as a control. These results can help us to better understand and design biodegradable films for agricultural mulching practices.

Amino acid and peptide couplings are widely used in fields related to pharma and materials. Still, current peptide synthesis continues to rely on the use of expensive, water sensitive, and waste-generating coupling reagents, which are often prepared in multi-step sequences and used in excess. Herein is described a peptide coupling reaction design that relies mechanistically on sun-light activation of a 4-dimethylamino-pyridine-alkyl halide charge-transfer complex to generate a novel coupling reagent in situ. The resulting coupling method is rapid, does not require dry solvents or inert atmosphere, and is compatible with all the most common amino acids and protecting groups. Peptide couplings can be run on gram-scale, without the use of special equipment. This method has a significantly reduced environmental and financial footprint compared to standard peptide coupling reactions. Experimental and computational studies support the proposed mechanism.

Diels-Alder (DA) reactions can be easily triggered by mere heating, sparing catalysts or stimulus, that are widely used in Covalent Adaptable Networks (CANs). Such CANs are used for making recyclable crosslinked materials due to their dynamic covalent networks. Herein we report the preparation and characterization of novel thermally switchable polymers capable of transitioning from thermo-reversibly self-healing hybrid polymers (re-CP-co-BMI) into irreversibly highly crosslinked networks with higher flame-retardancy (i-CP-co-BMI). Re-CP-co-BMI is characterized by excellent self-healing properties and reprocess-ability originating from DA/rDA reaction between maleimide of 4,4 '-bismaleimidodiphenylmethane (BMI) and furan of cyclotriphosphazene bearing three allyl and three furan groups (CP-3AF). The DA reaction proceeds in the melt, avoiding the need for additives, such as solvents and catalysts. At higher temperatures, irreversible alkene addition reactions are triggered by reactions between maleimide groups of BMI and allyl groups of CP-3AF, forming i-CP-co-BMI. This polymer is characterized by outstanding flame retardancy with 30.4% limiting oxygen index (LOI) and V-0 grade in the UL-94 test. Such a convenient synthesis and flexible structure design of phosphazene will open new windows for CANs with tunable properties.

Modulation of the H-bond basicity (pKHB) of various functional groups (FGs) by attaching fluorine functions and its impact on lipophilicity and bioisosterism considerations are described. In general, H/F replacement at the α-position to H-bond acceptors leads to a decrease of the pKHB value, resulting, in many cases, in a dramatic increase in the compounds' lipophilicity (log Po/w). In the case of α-CF2H, we found that these properties may also be affected by intramolecular H-bonds between CF2H and the FG. A computational study of ketone and sulfone series revealed that α-fluorination can significantly affect overall polarity, charge distribution, and conformational preference. The unique case of α-di- and trifluoromethyl ketones, which exist in octanol/water phases as ketone, hemiketal, and gem-diol forms, in equilibrium, prevents direct log Po/w determination by conventional methods, and therefore, the specific log Po/w values of these species were determined directly, for the first time, using Linclau's 19F NMR-based method.

A peptide coupling method that relies on sunlight activation of a 4-dimethylaminopyridine–alkyl halide charge-transfer complex for the in situ generation of a novel coupling reagent is described by Yoav Eichen, Alex M. Szpilman, and co-workers in their Research Article on page 12406. The reaction is rapid, water- and oxygen-tolerant, and compatible with all common amino acids and protective groups. It is characterized by a significantly reduced environmental, energetical, and economic footprint compared to standard peptide coupling reactions.

During the last few years, we have been exploring the potential of aqueous methylcellulose solutions as materials which can absorb the energy of shocks and mechanical impacts. This paper provides an overview of the key steps of this exploration, which includes the basic mechanical properties of methylcellulose hydrogels, the mechanism by which solutions of methylcellulose are thought to perform the impact-energy mitigation, and some more advanced work in compositing these materials with additives whose role is to improve performance in fields requiring a significant material response and high attenuation of shock energy.

Solutions of α-cyclodextrin in chiral 1-phenylethylamine display abnormal phase transitions. Depending on supramolecular diastereomeric interactions, inverse-melting and re-entrant gels are formed.

Shock mitigation performance of aqueous methylcellulose hydrogel and water for structural applications was investigated through two dynamic loading instruments: Instrumented bar and shock tube. While aqueous methylcellulose solutions have previously been found to attenuate impact-induced forces passing through them by a unique liquid-to-solid phase transition, this is the first time studied as shock mitigators to structural elements. The results obtained with aqueous methylcellulose as mitigator were compared with an equivalent experiment conducted with water as damping medium. The liquid was loaded into a specially designed hollow aluminum box, built to allow transmission of dynamic stress waves to a thin back plate. Determination of the liquid's attenuation performance was based on the 3D Digital Image Correlation technique with high-speed photography to obtain the full-field real-time deformation data of the back-face plate throughout the dynamic loading event. It was found that upon high rate loading with the instrumented bar, the aqueous methylcellulose solution decreases the maximum out of plane displacement resulting from the dynamic loading by as much as 40% compared to water, and significantly damps the structural vibrations of the back-face plate. On the other hand, upon relatively low rate loading with shock tubes, water and aqueous methylcellulose solutions provide the same magnitude of out of plane displacement, however, the damping ratio (Logarithmic Decrement) of the structure through aqueous methylcellulose solutions is 45% greater than through water. The findings are analyzed and rationalized in terms of imparted mechanical power.