Recognition-Encoded Molecules: a Minimal Self-Replicator.

Nucleic acids, with their unique duplex structure, which is key for information replication, have sparked interest in self-replication's role in life's origins. Early template-based replicators, initially built on short oligonucleotides, expanded to include peptides and synthetic molecules. We explore here the potential of a class of synthetic duplex-forming oligoanilines, as self-replicators. We have recently developed oligoanilines equipped with 2-trifluoromethylphenol-phosphine oxide H-bond base pairs and we investigate whether the imine formed between aniline and aldehyde complementary monomers can self-replicate. Despite lacking a clear sigmoidal kinetic profile, control experiments with a methylated donor and a competitive inhibitor support self-replication. Further investigations with the reduced aniline dimer demonstrate templated synthesis, revealing a characteristic parabolic growth. After showing sequence selective duplex formation, templated synthesis and the emergence of catalytic function, the self-replication behaviour further suggests that the unique properties of nucleic acids can be paralleled by synthetic recognition-encoded molecules.

Design, Synthesis, and Applications of Bis-Amido HPLC Pirkle-Type Chiral Stationary Phases.

Two different types of chiral stationary phases, based on Pirkle's design, were created by attaching chiral selectors to 3-mercapto silica gel. To prepare the enantiomeric selectors, 3,5-dinitrobenzoyl and naphthyl groups were sequentially added to a chiral 1,2-diaminocyclohexane core. The chiral selectors demonstrated enantioselectivity towards ibuprofen enantiomers in solution, as confirmed by 1H NMR spectroscopy, and in initial HPLC testing, the enantiomeric selectors showed enantioselectivity for selected racemic solutes (viz., α = 1.27 for1,1'-bi-(2-naphthol)). Molecular docking studies revealed that the chiral selectors had a bent structure and a cleft-like cavity where the analyte could be held during complexation while establishing H-bonding and π-π stacking interactions.

Towards Nickel-NHC Fluoro Complexes-Synthesis of Imidazolium Fluorides and Their Reactions with Nickelocene.

While hundreds of complexes of the general formula [Ni(η5-C5H5)(NHC)(X)] exist (NHC = a N-heterocyclic carbene, X = Cl, Br, I), none is yet known with X = F. We attempted to prepare such a species by reacting nickelocene with imidazolium fluorides. Three imidazolium fluorides (ImH)+ F- [Im = (N,N'-bis-(R)-imidazolium: 1a, IMe, R = Me; 1b, IMes, R = 2,4,6-trimethylphenyl; 1c, IPr, R = 2,6-diisopropylphenyl)] were prepared and characterized by spectroscopic methods. In addition, the salts 1b [(IMesH)+ F-] and 1c [(IPrH)+ F-] were subjected single-crystal X-ray diffraction experiments. The reactions of these imidazolium fluorides with nickelocene did not lead to [Ni(η5-C5H5)(NHC)(F)] species. Instead, the reaction of 1a [(IMeH)+ F-] and 1b [(IMesH)+ F-] with nickelocene led to the salt 2 [Ni(η5-C5H5)(IMe)2]+ F- and to the square planar complex 3atrans-[NiF2(IMes)2] respectively. Both complexes were characterized spectroscopically and by single crystal X-ray diffraction. All four X-ray diffraction studies reveal hydrogen bonding and hydrogen interactions with the F atom or anion, and in some cases with solvent molecules of crystallization, and these phenomena are all discussed. Complex 2, in particular, exhibited a wide range of interesting H-bonded interactions in the solid state. Complexes 2 and 3a were tested as catalysts for Suzuki-Miyaura coupling but were not promising: complex 2 was inactive, and while 3a did indeed catalyze the reaction, it gave widely diverging results owing to its instability in solution.

A General Photoactive H-Bonding EDA Complex Model Drives the Selective Hydrothiolation and Hydroxysulfenylation of Carbonyl Activated Alkenes.

Excitation of photoactive electron donor-acceptor (EDA) complexes to generate radical is a promising approach in radical chemistry. In this study, we introduce a new model of H-bonding EDA complexes for the selective hydrothiolation and hydroxysulfenylation of carbonyl-activated alkenes with diverse thiols under visible light conditions. The reliability of this H-bonding EDA complex model has been confirmed by meticulous experimental and theoretical calculations. Mechanistic investigations have revealed the significant influence of the solvent in determining whether the excitation of photoactive H-bonding EDA complex leads to charge transfer (CT) or energy-charge transfer (En-CT), thereby controlling Markovnikov and anti-Markovnikov selectivity. Notably, the Quantum Theory of Atoms in Molecules (QTAIM) analysis clearly shows that the excited state of the C=O-H-S EDA complex involves closed-shell partially covalent interactions.

Photoredox Catalytic Deracemization Enabled Enantioselective and Modular Access to Axially Chiral N-Arylquinazolinones.

Visible light-driven photocatalytic deracemization is highly esteemed as an ideal tool for organic synthesis due to its exceptional atom economy and synthetic efficiency. Consequently, successful instances of deracemization of allenes have been established, where the activated energy of photosensitizer should surpass that of the substrates, representing an intrinsic requirement. Accordingly, this method is not applicable for axially chiral molecules with significantly high triplet energies. In this study, we present a photoredox catalytic deracemization approach that enables the efficient synthesis of valuable yet challenging-to-access axially chiral 2-azaarene-functionalized quinazolinones. The substrate scope is extensive, allowing for both 3-axis and unmet 1-axis assembly through facile oxidation of diverse central chiral 2,3-dihydroquinazolin-4(1H)-ones that can be easily prepared and achieve enantiomer enrichment via deracemization. Mechanistic studies reveal the importance of photosensitizer selection in attaining excellent chemoselectivity and highlight the indispensability of a chiral Brønsted acid in enabling highly enantioselective protonation to accomplish efficient deracemization.

Ethyl 2-[(2-oxo-2H-chromen-6-yl)-oxy]acetate.

Ethyl 2-[(2-oxo-2H-chromen-6-yl)-oxy]acetate, C13H12O5, a member of the pharmacologically important class of coumarins, crystallizes in the monoclinic C2/c space group in the form of sheets, within which mol-ecules are related by inversion centers and 21 axes. Multiple C-H⋯O weak hydrogen-bonding inter-actions reinforce this pattern. The planes of these sheets are oriented in the approximate direction of the ac face diagonal. Inter-sheet inter-actions are a combination of coumarin system π-π stacking and additional C-H⋯O weak hydrogen bonds between ethyl acet-oxy groups.

A theoretical study of the photochemistry of 1,3-cyclopentadiene and its cyano derivatives bound to a water dimer: Assessing reactivity of ionized clusters and possible photoproducts.

We theoretically investigate the photoionization scenarios of molecular complexes involving cyclopentadiene and cyanocyclopentadiene bound to water dimers. Using electronic structure calculations within density-functional theory (DFT) and time dependent DFT (TD-DFT), we explore the potential photochemical pathways following ionization, and determine the charge transfer excitations related to the possible subsequent reactions. Our findings suggest that the investigated photochemical pathways of the hydrated complexes take place in two well-defined ultraviolet regions: (i) 8.2-9.5 eV for the cyclic compounds and (ii) 11.2-11.4 eV for the bound water dimer. We quantify how H-bonding effects can influence the photoionization channels. Before forming possible photoproducts, we also examine the regiospecificity of OH addition to 1,3-cyclopentadiene and its cyano derivatives We analyze our results in light of photoionization studies of jet-cooled molecular complexes and possible implications in astrochemical environments.

Bioinspired H-Bonding Connected Gradient Nanostructure Actuators Based on Cellulose Nanofibrils and Graphene.

The construction of flexible actuators with ultra-fast actuation and robust mechanical properties is crucial for soft robotics and smart devices, but still remains a challenge. Inspired by the unique mechanism of pinecones dispersing seeds in nature, a hygroscopic actuator with interlayer network-bonding connected gradient structure is fabricated. Unlike most conventional bilayer actuator designs, the strategy leverages biobased polyphenols to construct strong interfacial H-bonding networks between 1D cellulose nanofibers and 2D graphene oxide, endowing the materials with high tensile strength (172 MPa) and excellent toughness (6.64 MJ m-3). Furthermore, the significant difference in hydrophilicity between GO and rGO, along with the dense interlayer H-bonding, enables ultra-fast water exchange during water absorption and desorption processes. The resulted actuator exhibits ultra-fast driving speed (154° s-1), excellent pressure-resistant and cyclic stability. Taking advantages of these benefits, the actuator can be fabricated into smart devices (such as smart grippers, humidity control switches) with significant potential for practical applications. The presented approach to constructing interlayer H-bonding in gradient structures is instructive for achieving high performance and functionalization of biomass nanomaterials and the complex of 1D/2D nanomaterials.

Cyclometallated Imides as Templates for the H-Bond Directed Iridium-Catalyzed Asymmetric Hydrogenation of N-Methyl, N-Alkyl and N-Aryl Imines.

A combined computational and experimental approach allowed us to develop overall the most selective catalyst for the direct hydrogenation of N-methyl, N-alkyl and N-aryl imines described to date. Iridium catalysts with a cyclometallated cyclic imide group provide selectivity of up to 99 % enantiomeric excess. Computational studies show that the selectivity results from the combined effect of H-bonding of the imide C=O with the substrate iminium ion and a stabilizing π-π interaction with the cyclometallated ligand. The cyclometallated ligand thus exhibits a unique mode of action, serving as a template for the H-bond directed approach of the substrate which results in enhanced selectivity. The catalyst (2) has been synthesized and isolated as a crystalline air-stable solid. X-ray analysis of 2 confirmed the structure of the catalyst and the correct position of the imide C=O groups to engage in an H-bond with the substrate. 19F NMR real-time monitoring showed the hydrogenation of N-methyl imines catalyzed by 2 is very fast, with a TOF of approx. 3500 h-1.

Enhanced Reactivities of Iron(IV)-Oxo Porphyrin Species in Oxidation Reactions Promoted by Intramolecular Hydrogen-Bonding.

High-valent iron-oxo species are one of the common intermediates in both biological and biomimetic catalytic oxidation reactions. Recently, hydrogen-bonding (H-bonding) has been proved to be critical in determining the selectivity and reactivity. However, few examples have been established for mechanistic insights into the H-bonding effect. Moreover, intramolecular H-bonding effect on both C-H activation and oxygen atom transfer (OAT) reactions in synthetic porphyrin model system has not been investigated yet. In this study, a series of heme-containing iron(IV)-oxo porphyrin species with or without intramolecular H-bonding are synthesized and characterized. Kinetic studies revealed that intramolecular H-bonding can significantly enhance the reactivity of iron(IV)-oxo species in OAT, C-H activation, and electron-transfer reactions. This unprecedented unified H-bonding effect is elucidated by theoretical calculations, which showed that intramolecular H-bonding interactions lower the energy of the anti-bonding orbital of iron(IV)-oxo porphyrin species, resulting in the enhanced reactivities in oxidation reactions irrespective of the reaction type. To the best of the knowledge, this is the first extensive investigation on the intramolecular H-bonding effect in heme system. The results show that H-bonding interactions have a unified effect with iron(IV)-oxo porphyrin species in all three investigated reactions.

Deliver on a Promise: Hydrogen-Bonded Polymer Nanomedicine with a Precise Ratio of Chemodrug and Photosensitizer for Intelligent Cancer Therapy.

The outcomes of combined cancer therapy are largely related to loading content and contribution of each therapeutic agent; however, fine-tuning the ratio of two coloaded components toward precise cancer therapy is a great challenge and still remains in its infancy. We herein develop a supramolecular polymer scaffold to optimize the coloading ratio of chemotherapeutic agent and photosensitizer through hydrogen-bonding (H-bonding) interaction, for maximizing the efficacy of intelligent cancer chemo/photodynamic therapies (CT/PDT). To do so, we first synthesize a thymine (THY)-functionalized tetraphenylporphyrin photosensitizer (i.e., TTPP), featuring the same molecular configuration of H-bonding array with chemotherapeutic carmofur (e.g., 1-hexylcarbamoyl-5-fluorouracil, HCFU). Meanwhile, a six-arm star-shaped amphiphilic polymer vehicle P(DAPA-co-DPMA-co-OEGMA)6 (poly(diaminopyridine acrylamide-co-2-(diisopropylamino)ethyl methacrylate-co-oligo(ethylene glycol) monomethyl ether methacrylate)6) is prepared, bearing hydrophilic and biocompatible POEGMA segment, along with hydrophobic PDAPA and PDPMA segments, characterizing the randomly dispersed dual functionalities, i.e., heterocomplementary H-bonding DAP motifs and pH-responsive protonation DPMA content. Thanks to the identical DAP/HCFU and DAP/TTPP H-bonding association capability, the incorporation of both HCFU and TTPP to six-arm star-shaped P(DAPA-co-DPMA-co-OEGMA)6 vehicle, with an optimized coloading ratio, can be straightforwardly realized by adjusting the feeding concentrations, thus yielding the hydrogen-bonded supramolecular nanoparticles (i.e., HCFU-TTPP-SPNs), demonstrating the codelivery of two components with the promise to optimize the combined CT/PDT efficacy.

Multiple H-Bonding Cross-Linked Supramolecular Solid-Solid Phase Change Materials for Thermal Energy Storage and Management.

Solid-solid phase change materials (SSPCMs) are considered among the most promising candidates for thermal energy storage and management. However, the application of SSPCMs is consistently hindered by the canonical trade-off between high TES capacity and mechanical robustness. In addition, they suffer from poor recyclability due to chemical cross-linking. Herein, a straightforward but effective strategy for fabricating supramolecular SSPCMs with high latent heat and mechanical strength is proposed. The supramolecular polymer employs multiple H-bonding interactions as robust physical cross-links. This enables SSPCM with a high enthalpy of phase transition (142.5 J g-1 ), strong mechanical strength (36.9 MPa), and sound shape stability (maintaining shape integrity at 120 °C) even with a high content of phase change component (97 wt%). When SSPCM is utilized to regulate the operating temperature of lithium-ion batteries, it significantly diminishes the battery working temperature by 23 °C at a discharge rate of 3 C. The robust thermal management capability enabled through solid-solid phase change provides practical opportunities for applications in fast discharging and high-power batteries. Overall, this study presents a feasible strategy for designing linear SSPCMs with high latent heat and exceptional mechanical strength for thermal management.

Urea-Functionalized Heterocycles: Structure, Hydrogen Bonding and Applications.

Ureido-heterocycles exhibiting different triple- and quadruple H-bonding patterns are useful building blocks in the construction of supramolecular polymers, self-healing materials, stimuli-responsive devices, catalysts and sensors. The heterocyclic group may provide hydrogen bond donor/acceptor sites to supplement those in the urea core, and they can also bind metals and can be modified by pH, redox reactions or irradiation. In the present review, the main structural features of these derivatives are discussed, including the effect of tautomerization and conformational isomerism on self-assembly and complex formation. Some examples of their use as building blocks in different molecular architectures and supramolecular polymers, with special emphasis on biomedical applications, are presented. The role of the heterocyclic functionality in catalytic and sensory applications is also outlined.

The Role H-Bonding and Supramolecular Structures in Homogeneous and Enzymatic Catalysis.

The article analyzes the role of hydrogen bonds and supramolecular structures in enzyme catalysis and model systems. Hydrogen bonds play a crucial role in many enzymatic reactions. However, scientists have only recently attempted to harness the power of hydrogen bonds in homogeneous catalytic systems. One of the newest directions is associated with attempts to control the properties of catalysts by influencing the "second coordination sphere" of metal complexes. The role H-bonding, and the building of stable supramolecular nanostructures due to intermolecular H-bonds, based on catalytic active heteroligand iron (Fe) or nickel (Ni) complexes formed during hydrocarbon oxidations were assessed via the AFM (Atomic-force microscopy) method, which was proposed and applied by authors of this manuscript. Th is article also discusses the roles of hydrogen bonds and supramolecular structures in oxidation reactions catalyzed by heteroligand Ni and Fe complexes, which are not only effective homogeneous catalysts but also structural and functional models of Oxygenases.

Hydrogen Bonds Stabilize Chloroselenite Anions: Crystal Structure of a New Salt and Donor-Acceptor Bonding to SeO2.

The single-crystal X-ray diffraction structure characterizing a new 4-methylbenzamidinium salt of chloroselenite [C8H11N2][ClSeO2] is reported. This is only the second crystal structure report on a ClSeO2- salt. The structure contains an extended planar hydrogen bond net, including a double interaction with both O atoms of the anion (an R228 ring in Etter notation). The anion has the shortest Se-Cl distances on record for any chloroselenite ion, 2.3202(9) Å. However, the two Se-O distances are distinct at 1.629(2) and 1.645(2) Å, attributed to weak anion-anion bridging involving the oxygen with the longer bond. DFT computations at the RB3PW91-D3/aug-CC-pVTZ level of theory reproduce the short Se-Cl distance in a gas-phase optimized ion pair, but free optimization of ClSeO2- leads to an elongation of this bond. A good match to a known value for [Me4N][ClSeO2] is found, which fits to the Raman spectroscopic evidence for this long-known salt and to data measured on solutions of the anion in CH3CN. The assignment of the experimental Raman spectrum was corrected by means of the DFT-computed vibrational spectrum, confirming the strong mixing of the symmetry coordinate of the Se-Cl stretch with both ν2 and ν4 modes.

First mesomorphic and DFT characterizations for 3- (or 4-) n-alkanoyloxy benzoic acids and their optical applications.

New liquid crystalline hydrogen bonded 3- (or 4)-n-alkanoyloxy benzoic acids were synthesized and probed theoretically and experimentally. The molecular structures of these compounds were elucidated by proton NMR, carbon-13 NMR and elemental analyses. Differential scanning calorimetry (DSC) was used to investigate the thermal and mesomorphic properties of all the symmetrical dimers that bearing identical alkanoyloxy chains. Moreover, polarized optical microscopy (POM) was used to determine their mesophases. The findings show that all the designed symmetrical dimers exhibit the smectic mesophase with relative thermal stability that depends on the length of their terminal side chain. Additionally, the experimental findings of the mesomorphic behavior are further supported by DFT calculations. The alkanoyloxy benzoic acid para-derivatives (In) were shown to be more stable than their meta-substituted (IIn) analogues due to stronger hydrogen bonding interactions. The computed reactivity parameters showed that the position of ester moiety has a significant impact on the acids reactivity. The absorbance spectra of both the 3- (or 4)-n-alkanoyloxy benzoic acids revealed a blue shift with the increment of the of alkyl chain size; however, the energy band gaps of 3-n-alkanoyloxy benzoic derivatives were found to be slightly higher than those of the 4-n-alkanoyloxy benzoic acids. Moreover, the photoluminescence spectrum of the prepared materials is rather broad, and exhibited a red shift as the alkyl chain length increases. The fluorescence lifetime shown to rise as alkyl chain length grows longer, and 3-n-alkanoyloxy benzoic acids have slightly longer lifetime compared to their 4-n-alkanoyloxy benzoic analogues.

Water-Soluble Squaramide-Functionalized Copolymers for Anion Recognition.

A series of ethylene glycol-based squaramide-containing copolymers are synthesized via a post-polymerization functionalization strategy. Conversion of polymeric amines to squaramides is found to proceed in good yields, representing a versatile method of incorporating squaramides into polymers for anion recognition. Analysis of the polymers by UV-Vis and fluorescence spectroscopy revealed that anion binding takes place similarly to that of small-molecule squaramides. The presence of a fluorescent sensing group on polymer-bound squaramides allowed for a fluorescent sensing mechanism for anions that followed a similar trend in selectivity in aqueous DMSO solution, with selectivity observed for H2 PO4 - , AcO- and SO4 2- over other common anions tested. The anion response and selectivity towards anions is similar to that of analogous small-molecule squaramides, however polymeric squaramides exhibited a greater resistance to deprotonation by more basic anions, which is attributed to the closer proximity of individual squaramides on a macromolecule. The squaramide-containing polymers exhibited good water solubility, overcoming a common problem for anion sensors which are typically not sufficiently soluble in water to function in many required applications. Despite no anion binding being observed in water, this study represents a simple and effective method of creating fully water-soluble anion receptors which may be adapted to give improved binding affinity and selectivity depending on the anion binding moiety.

A General Strategy Toward pH-Resistant Phenolic Fluorophores for High-Fidelity Sensing and Bioimaging Applications.

Aryl alcohol-type or phenolic fluorophores offer diverse opportunities for developing bioimaging agents and fluorescence probes. Due to the inherently acidic hydroxyl functionality, phenolic fluorophores provide pH-dependent emission signals. Therefore, except for developing pH probes, the pH-dependent nature of phenolic fluorophores should be considered in bioimaging applications but has been neglected. Here we show that a simple structural remedy converts conventional phenolic fluorophores into pH-resistant derivatives, which also offer "medium-resistant" emission properties. The structural modification involves a single-step introduction of a hydrogen-bonding acceptor such as morpholine nearby the phenolic hydroxyl group, which also leads to emission bathochromic shift, increased Stokes shift, enhanced photo-stability and stronger emission for several dyes. The strategy greatly expands the current fluorophores' repertoire for reliable bioimaging applications, as demonstrated here with ratiometric imaging of cells and tissues.

Co-Crystallization: A Novel Technique to Improvise the Pharmaceutical Characteristics of API's.

BACKGROUND: The poor water solubility of an active pharmaceutical ingredient leads to a lower dissolution profile that in turn results in poor bioavailability of drugs. Various approaches like solid dispersion, nano-technology, complexation, and micronization techniques, etc. are frequently used by pharmaceutical researchers to overcome these issues. In this context, crystal engineering emerges as a viable technique. OBJECTIVE: This review endeavors to cover the latest developments in the field of solubility enhancement using crystal engineering techniques. METHODS: Extensive literature survey was conducted in order to gain information on the past and present developments in the field of crystal engineering. RESULTS: In the co-crystallization process, the API and coformer interact with each other in a fixed stoichiometric ratio. The backbone of co-crystals is structurally repeating units called supramolecular synthons. These synthons provide the flexibility of transfer from one co-crystal system to another, making crystal engineering a viable approach for physicochemical property modification. Further, the availability of a large number of food and drug grade coformers with a diverse functional group and a range of preparation methods provide an excellent opportunity for tuning up desired physicochemical properties of an API. CONCLUSION: This review focuses on the latest developments in the field of crystal engineering in the context of screening, preparation methods, characterization, and their application in the pharmaceutical field. Also, the concern over scale-up and regulatory guidelines are covered.

A smartphone-based visual ratiometric fluoroprobe for rapid and sensitive detection hypochlorous acid based on dual-emission metal organic frameworks.

Herein, we designed/developed a mixed fluorescence system with europium metal-organic framework (EDB) and zinc metal-organic framework (ZBNB). At the 270-nm excitation wavelength, the EDB-ZBNB dually emitted at 425 and 615 nm and displayed blue solution under 365-nm UV lamp. When HOCl was fortified, the 425-nm blue emission dropped progressively, while the 615-nm red emission was relatively stable. Upon addition of ClO-, the shortened fluorescence lifetime demonstrated that the quenched 425-nm fluorescence of ZBNB was owing to the occurrence of dynamic quenching effect. Besides, amino groups are protonated in water to form -NH3+, which interact with ClO- to form hydrogen bonds, reduce the distance between -NH3+ and ClO-, produce energy transfer and result in fluorescence quenching. The ratiometric fluoroprobe provided a significant color change from blue to red, making HOCl detection visual and rapid. This fluorescent probe overcome the disadvantage of conventional redox-based fluorescent probes that can be interfered by MnO4- and other oxidants with stronger oxidizing capacity than free ClO-. Furthermore, a smartphone-based portable sensing platform was developed based on EDB-ZBNB. By using a "Thingidentify" software on smartphone, the sensing platform was used to detect HOCl in waters with a low detection limit of 28.0 nM and the fortified recoveries of 98.87-103.60%. Thus, this study provides a novel and promising platform for the detection of free ClO- in monitoring water quality.