Multiple Hydrogen Bond Donors Research Articles

Structure Elucidation of Pharmaceutically Relevant Compounds Within Pyrene-Based Frameworks.

Single-crystal X-ray diffraction (SCXRD) is the preferred and most accurate technique for determining molecular structures. However, it can present challenges when dealing with specific small molecules and active pharmaceutical ingredients (APIs), as many do not form quality crystals without coformers or can be unstable. In this study, we introduce tetrakis(guanidinium) pyrenetetrasulfonate (G4PYR), a robust guanidinium-organosulfonate (GS) framework that efficiently encapsulates small molecules and APIs rich in functional groups. The hydrogen bonding frameworks formed by G4PYR display well-ordered structures with predictable pyrene-pyrene distances, making them ideally suited for targeting arene-based APIs with pendant groups. Successful encapsulation of various guests, including benzaldehyde, benzamide, and arenes containing multiple hydrogen bond donors and acceptors like uracil and thymine, was achieved. Furthermore, we successfully encapsulated important pharmaceutical and biologically relevant compounds, such as lidocaine, ropinirole, adenosine, thymidine, and others. Notably, we present a workflow for investigating host-guest complex formation using powder X-ray diffraction and high throughput experimentation.

Structural insights into supramolecular interactions in isostructural salts of 2,4,6-triaminopyrimidinium with various heterocyclic carboxylates.

2,4,6-Triaminopyrimidine is an interesting and challenging molecule due to the presence of multiple hydrogen-bond donors and acceptors. Its noncovalent interactions with a variety of carboxylic acids provide several supramolecular aggregates with frequently occurring molecular synthons. The present work focuses on the supramolecular interactions of 2,4,6-triaminopyrimidinium 3-(indol-3-yl)propionate-3-(indol-3-yl)propionic acid (1/1), C4H8N5+·C11H10NO2-·C11H11NO2, (I), 2,4,6-triaminopyrimidinium 2-(indol-3-yl)acetate, C4H8N5+·C10H8NO2-, (II), 2,4,6-triaminopyrimidinium 5-bromothiophene-2-carboxylate, C4H8N5+·C5H2BrO2S-, (III), and 2,4,6-triaminopyrimidinium 5-chlorothiophene-2-carboxylate, C4H8N5+·C5H2ClO2S-, (IV). All four salts exhibit robust homomeric and heteromeric R22(8) ring motifs. Salts (I) and (II) develop sextuple [in (I)] and quadruple [in (I) and (II)] hydrogen-bonded arrays through fused-ring motifs. Salt (II) exhibits a rosette-like architecture. Salt (IV) is isostructural and isomorphous with salt (III), exhibiting an identical crystal structure with a different composition and an identical supramolecular architecture. In salts (III) and (IV), a linear hetero-tetrameric motif is formed and, in addition, both salts exhibit halogen-π interactions which enhance the crystal stability. All four salts develop a supramolecular hydrogen-bonded pattern facilitated by several N-H...O and N-H...N hydrogen bonds with multiple furcated donors and acceptors.

Sea Cucumber-Inspired Polyurethane Demonstrating Record-Breaking Mechanical Properties in Room-Temperature Self-Healing Ionogels.

Practical applications of existing self-healing ionogels are often hindered by the trade-off between their mechanical robustness, ionic conductivity, and temperature requirements for their self-healing ability. Herein, this challenge is addressed by drawing inspiration from sea cucumber. A polyurethane containing multiple hydrogen-bond donors and acceptors is synthesized and used to fabricate room-temperature self-healing ionogels with excellent mechanical properties, high ionic conductivity, puncture resistance, and impact resistance. The hard segments of polyurethane, driven by multiple hydrogen bonds, coalesce into hard phase regions, which can efficiently dissipate energy through the reversible disruption and reformation of multiple hydrogen bonds. Consequently, the resulting ionogels exhibit record-high tensile strength and toughness compared to other room-temperature self-healing ionogels. Furthermore, the inherent reversibility of multiple hydrogen bonds within the hard phase regions allows the ionogels to spontaneously and efficiently self-heal damaged mechanical properties and ionic conductivity multiple times at room temperature. To underscore their application potential, these ionogels are employed as electrolytes in the fabrication of electrochromic devices, which exhibit excellent and stable electrochromic performance, repeatable healing ability, and satisfactory impact resistance. This study presents a novel strategy for the fabrication of ionogels with exceptional mechanical properties and room-temperature self-healing capability.

Enhanced aggregation induced emission by H-bond between the barbiturate molecules containing hydroxyl group

Barbiturates had been widely studied as a molecule with aggregation induced emission (AIE) phenomenon, but barbiturates as a group with multiple hydrogen bond donor and acceptor sites, the relationship between intermolecular hydrogen bond and AIE phenomenon has not been mainly studied. In this paper, a new barbiturate fluorescence molecule BNOH with hydroxyl group was designed and synthesized in order to analyze the relationship between hydrogen bond and molecular AIE phenomenon by increasing the functional group (–OH) that was easy to form hydrogen bond. By spectroscopic analysis, BNOH had structural torsion in aqueous mixed solution, which led to fluorescence decrease, while in aprotic mixed solvent, there was strong AIE phenomenon. DFT and TD-DFT calculations at the B3LYP/6-31G (d) were performed for a deeper understanding of optical transitions. In addition, in order to investigate the difference of its fluorescence phenomenon, two other barbiturate derivatives were synthesized and their spectra were compared with BNOH. The relationship between hydrogen bond and AIE phenomenon of barbiturates was proved, and the fluorescence mechanism of BNOH in organic solvent was proposed and determined. We believe that this study will not only increase the understanding of barbiturate AIE compounds, but also contribute to the study of the important role of hydrogen bonds in the fluorescence phenomenon of barbiturate AIE compounds.

Mechanism of solvent-mediated polymorphic transformation to prepare axitinib form XLI controlled by water activity

Axitinib (AXI) is widely used in the treatment of renal cancer. Due to its molecule structure containing multiple hydrogen bond acceptors and donors, AXI has been reported five solvent-free polymorphs...

Nonlinear and Emissive {[MIII(CN)6]3-···Polyresorcinol} (M = Fe, Co, Cr) Cocrystals Exhibiting an Ultralow Frequency Raman Response.

Optically active functional noncentrosymmetric architectures might be achieved through the combination of molecules with inscribed optical responses and species of dedicated tectonic character. Herein, we present the new series of noncentrosymmetric cocrystal salt solvates (PPh4)3[M(CN)6](L)n·msolv (M = Cr(III), Fe(III), Co(III); L = polyresorcinol coformers, multiple hydrogen bond donors: 3,3',5,5'-tetrahydroxy-1,19-biphenyl, DiR, n = 2, or 5'-(3,5-dihydroxyphenyl)-3,3″,5,5″-tetrahydroxy-1,19:3',1″-terphenyl, TriRB, n = 1) denoted as MDiR and MTriRB, respectively. The hydrogen-bonded subnetworks {[M(CN)6]3-;Ln}∞ of dmp, neb, or dia topology are formed through structural matching between building blocks within supramolecular cis-bis(chelate)-like {[M(CN)6]3-;(H2L)2(HL)2} or tris(chelate)-like {[M(CN)6]3-;(H2L)3} fragments. The quantum-chemical analysis demonstrates the mixed electrostatic and covalent character of these interactions, with their strength clearly enhanced due to the negative charge of the hydrogen bond acceptor metal complex. The corresponding interaction energy is also dependent on the geometry of the contact and size matching of its components, rotational degree of freedom and extent of the π-electron system of the coformer, and overall fit to the molecular surroundings. Symmetry of the crystal lattices is correlated with the local symmetry of coformers and {complex;(coformer)n} hydrogen-bonded motifs characterized by the absence of the inversion center and mirror plane. All compounds reveal second-harmonic generation activity and photoluminescence diversified by individual UV-vis spectral characteristics of the components, and interesting low-frequency Raman scattering spectra within the subterahertz spectroscopic domain. Vibrational (infrared/Raman), UV-vis electronic absorption (experimental and calculated), and 57Fe Mössbauer spectra together with electrospray ionization mass spectrometry (ESI-MS) data are provided for the complete description of our systems.

Rigid macrocycles with multiple hydrogen-bond donors for effective anion binding and transport.

Rigid macrocycles with multiple hydrogen-bond donors for effective anion binding and transport.

Design and Application of Peptide-Mimic Phosphonium Salt Catalysts in Asymmetric Synthesis.

Chiral phosphonium salt catalysis, traditionally classified as a type of phase transfer catalysis, has proven to be a powerful strategy for the stereoselective preparation of diverse optically active molecules. However, there still remain numerous forbidding issues of reactivity and selectivity in such well-known organocatalysis system. Accordingly, the development of new and high-performance phosphonium salt catalysts with unique chiral backbones is highly desirable, yet challenging. This Minireview describes the prominent endeavours in the development of a new family of chiral peptide-mimic phosphonium salt catalysts with multiple hydrogen-bonding donors and their applications in a plethora of enantioselective synthesis during the past few years. Hopefully, this minireview will pave a way for further developing much more efficient and privileged chiral ligands/catalysts featuring exclusively catalytic ability in asymmetric synthesis.

Front Cover: Asymmetric Mannich/Radical Debromination Cascade of α‐Bromoketones by Dipeptide‐Phosphonium Salt Catalysis: Enantioselective Synthesis of β‐Amino Ketone‐Pyrazolinones (Asian J. Org. Chem. 6/2023)

Peptide-phosphonium salt (PPS) catalysts, which contain multiple hydrogen-bonding donors, have displayed remarkable phase-transfer catalytic efficiency in recent years. The cover art demonstrated that PPS catalysts can efficiently promote the enantioselective Mannich/radical debromination cascade of α-brominated ketones with pyrazolinone ketimines to access valuable chiral β-amino ketone-pyrazolinone scaffolds. This protocol would open new avenues for organocatalytic enantioselective radical reactions. More information can be found in the Research Article by Tianli Wang et al.

Asymmetric [3+2]-cyclization of α-imino amide surrogates to construct 3,4-diaminopyrrolidine-2,5-diones.

Using newly designed α-imino amide surrogates and azlactones as amphiphilic reactants, catalyzed by a chiral bifunctional guanidine, the construction of chiral 3,4-diaminopyrrolidine-2,5-diones and their derivatives was realized via formal [3+2]-cyclization. The role of guanidine as a multiple hydrogen bond donor was demonstrated by DFT calculations.

Hexaamminecobalt(III) Cation as Multiple Hydrogen Bond Donors: Synthesis, Characterization and Energetic Properties of cyclo-Pentazolate and Azide Based Complexes

A series of hexaaminocobalt(III) based energetic compounds [Co(NH3)6](N3)3 (1), [Co(NH3)6](N5)2(N3) (2), [Co(NH3)6](N5)3 (3), and their chloride and nitrate complex salts 4–6 were designed and synthesized by simple metathesis reactions. As far as we know, compound 3 is the first trivalent metal pentazolate salt. The structures of all the new energetic compounds were confirmed by single-crystal X-ray diffraction. Their physicochemical and energetic properties, such as density, thermal stability, sensitivity, and detonation properties, were also evaluated. Due to the extensive hydrogen bonding network, the detonation properties of these salts and acceptable mechanical sensitivities (IS = 3–6 J, FS = 40–80 N) hold the prospective potential as green primary explosives. This work suggests that the cyclo-pentazolate anion has good compatibility with azide and nitrate ions, and they can act together as hydrogen bond acceptors to form novel energetic materials with controllable properties through hydrogen bonds.

Triazinyl-imidazole polyamide network as an efficient multi-hydrogen bond donor catalyst for additive-free CO2 cycloaddition

A single-component synergistic catalytic system, in which multiple active sites act on a substrate with minimal energy input and promote efficient conversion of the substrate, is considered to be the most advanced technology for simulating enzyme catalytic reaction. The design principles of this technology are the driving force behind the pursuit of cost-effectiveness in industrial production, but the challenges remain formidable. Herein, three periodic mesoporous polyamides with triazine-derived networks (PMP-TDNs) were prepared via "one-pot" polycondensation, and used as non-metallic catalysts for cycloaddition of CO2 with epoxides without any additives to synthesis cyclic carbonates. The composition and physicochemical properties of PMP-TDNs were evaluated via different analytical methods to explore the crucial factors affecting catalytic activity. Especially, the activity of PMP-TDNs-MI with multiple hydrogen bond donor (HBD) and high-density N basic sites have been tested effectually; the results has demonstrated a superior reactivity for the cycloaddition of CO2 and a wide range of epoxides with reusability. The kinetics and thermodynamics of cycloaddition of CO2 with propylene epoxide by PMP-TDNS-MI were investigated, and the cooperative catalytic mechanism between the versatile active sites of catalyst was revealed based on the experimental results.

Rational self-assembly of triazine- and urea-functionalized periodic mesoporous organosilicas for efficient CO2 adsorption and conversion into cyclic carbonates

The development of advanced multifunctional nanomaterials for selective CO2 conversion remains a major challenge. Herein, novel triazine- and urea-functionalized periodic mesoporous organosilicas (TUF-PMOs) were constructed and structurally characterized by a facile hydrothermal self-assembly method. The obtained TUF-PMOs integrate multiple hydrogen bond donor and Lewis base sites, and have high surface area and well-ordered mesoporous channel. They were used for CO2 adsorption and catalyzing CO2/epoxide cycloaddition reaction. The effects of active group contents, various cocatalysts and reaction conditions on the cycloaddition reaction were examined. The optimum TUF-PMO-20 displays good bifunctionality for CO2 adsorption and conversion when combining with tetrabutylammonium iodide (TBAI) cocatalyst under mild and green conditions. Moreover, the TUF-PMO-20 catalyst shows exciting reusability and versatility. Finally a cooperating catalytic mechanism of TUF-PMO/TBAI system in CO2 cycloaddition reaction was provided. The present work provides a new avenue for the application of task-specific hybrid organosilicon materials in CO2 activation and conversion.

Development of Green Asymmetric Organocatalytic Synthesis

Organocatalysts, which are less toxic than metal catalysis, as well as inexpensive, environmentally benign, and stable against moisture and oxygen compared to metal-based catalysts, have received considerable attention for being efficient and clean catalysts. With respect to green chemistry, the development of organocatalysis is a significant research subject for a sustainable society. This article reviews studies on the development of novel organocatalysts and the reactions achieved from using them. Focusing on the push-pull ethylene moiety, in which two electron-withdrawing groups (EWGs) were introduced, we proposed that the vinylogous amide proton (N-H) will lead to the design of organocatalysts. We have developed the diaminomethylenemalononitrile (DMM) organocatalysts, which are push-pull ethylenes having two cyano groups as EWGs, and proved that they are effective for highly stereoselective hydrophosphonylation with aldehydes. The catalytic ability of the DMM organocatalyst was demonstrated in the development of the first asymmetric hydrophosphonylation of ketones using organocatalysts. The DMM organocatalyst can be applied to the selective 1,4-addition asymmetric hydrophosphonylation of enones. In addition, we designed and synthesized novel organocatalysts bearing squaramide-sulfonamide motif as multiple hydrogen bond donors. Squaramide-sulfonamide organocatalysts efficiently catalyzed the asymmetric direct vinylogous aldol reactions of furan-2(5H)-one with aldehydes. Successively, we achieved the synthesis of γ,γ-disubstituted-δ-hydroxy-γ-butenolide via asymmetric direct vinylogous aldol reaction of furanone derivatives using the squaramide-sulfonamide organocatalysts.

Molecular dynamics simulations of heterogeneous hydrogen bond environment in hydrophobic deep eutectic solvents

AbstractHydrophobic deep eutectic solvents (DESs) have emerged as excellent extractants. Their performance depends on the heterogeneous hydrogen bond environment formed by multiple hydrogen bond donors and acceptors. Understanding this heterogeneous hydrogen bond environment can help develop principles for designing high‐performance DESs for extraction and other separation applications. We investigate the structure and dynamics of hydrogen bonds in eight hydrophobic DESs formed by decanoic acid, menthol, thymol, and lidocaine using molecular dynamics simulations. The results show the diversity of hydrogen bonds in the eight DESs and their impact on diffusivity and molecular association. Each DES possesses four to six types of hydrogen bonds and one or two of them overwhelm the others in quantity and lifetime. The dominating hydrogen bonds determine whether the DESs are governed by intra‐ or inter‐component associations. The component diffusivity presents an inverse relationship with the hydrogen bond strength.

Fabrication of robust and bifunctional cyclotriphosphazene-based periodic mesoporous organosilicas for efficient CO2 adsorption and catalytic conversion

• Novel cyclotriphosphazene-based PMO-CPFs with tunable porosity are developed. • The PMO-CPFs show exciting dual-functions for CO 2 adsorption and conversion. • The PMO-CPF-catalyzed coupling reaction can perform under mild and green conditions. • The catalyst is easily separated and shows good structural stability and reusability. The design and development of advanced functional materials for efficient absorption and selective conversion of carbon dioxide (CO 2 ) remains a challenging research topic. In this work, novel cyclotriphosphazene-based periodic mesoporous organosilicas (PMO-CPF) with various contents of active components and tunable porosity were successfully prepared via direct co-condensation method, and their structures were characterized by FT-IR, solid-state 13 C, 29 Si and 31 P NMR, XRD, N 2 adsorption–desorption, HR-TEM and TGA techniques. The PMO-CPFs as-prepared were applied for CO 2 adsorption and conversion into cyclic carbonates, and the adsorption capacity and catalytic behaviors were thoroughly investigated. The PMO-CPFs integrate the structural features of high specific surface area, Lewis basic units and multiple dual hydrogen bond donor (HBD) groups, which endow the materials with dual functions of CO 2 adsorption and epoxide activation by forming dual hydrogen bonds. The optimum PMO-CPF-20 combining with tetrabutylammonium iodide (TBAI) showed an excellent activity for the cycloaddition of CO 2 to propylene oxide (PO), and could afford 98% propylene carbonate (PC) yield with above 99% selectivity under the conditions of 90 °C and 2.0 MPa for 6.0 h. Moreover, the catalyst reusability and applicability to epoxides with different substituents were studied, and a feasible catalytic mechanism was finally proposed. The developed metal-free, robust and bifunctional mesoporous organosilicas here were suggested to be advanced materials for CO 2 adsorption and subsequent catalytic conversion.

From Uncommon Ethylzinc Complexes Supported by Ureate Ligands to Water-Soluble ZnO Nanocrystals: A Mechanochemical Approach

Urea and its derivatives, due to their unusual versatility of coordination modes to metal centers and the presence of multiple hydrogen-bond donor sites, are widely utilized as neutral or monoanionic ligands in coordination and bioinorganic chemistry and as building units of bioinspired materials. However, metal complexes with ureate ligands have essentially not been applied as precursors of hybrid organic–inorganic nanomaterials. We report on the synthesis and structure characterization of two novel organozinc ureate complexes incorporating N-phenylureate or N,N′-dicyclohexylureate ligands, the latter being the first reported complex with the μ3-μ2(O):κ1(N) ureate coordination mode. These findings not only expand the horizon of urea–zinc chemistry but also pave the way for efficient bottom-up mechanochemical synthesis of sub-10 nm diameter zinc oxide nanocrystals (ZnO NCs) coated by the ureate ligands. We explored the NC formation triggered by mechanical force from both a well-defined monocrystalline precursor and an insoluble hard-to-process amorphous organozinc precursor. Moreover, the organic shell of the N-phenylureate-coated ZnO NCs was modified via a facile, fast, and solventless host–guest complexation with β-cyclodextrin using a mechanochemical approach, which afforded water-soluble ZnO NCs. The reported procedure is the first example of rapid and sustainable mechanochemical synthesis of hybrid nanomaterials from organometallic precursors.

Physicochemical Insights into the Role of Drug Functionality in Fibrillation Inhibition of Bovine Serum Albumin.

To revert amyloid fibrils to their native state is a challenge in finding a solution to prevent neurodegenerative diseases. We have adopted a structure-property-energetics correlation-based approach with drugs (5-fluorouracil and hydroxyurea) having multiple hydrogen-bond donors and acceptors as inhibitors targeting different stages of bovine serum albumin fibrillation. We present here a quantitative comprehensive biophysical approach for identifying functionalities in molecules, which offers this feature in terms of polarity and hydrogen bonding. Our objective of identifying the functionality on a drug molecule that establishes effective intermolecular hydrogen bonding with β-strands of protein fibrils was achieved by combined calorimetric, spectroscopic, volumetric, and microscopic correlations. Relationships have been established among thermodynamic signatures, F19-NMR chemical shifts, hydrodynamic diameters, and thermal expansion coefficients to demonstrate that the open-chain molecule is a better inhibitor of fibrillation, but its efficiency decreases with the formation of amorphous aggregates, as compared to the molecule having a uracil ring. The results have provided quantitative insights into the role of polarity and hydrogen bonding in prevention of the fibrillation process. The approach adopted here highlights the physical chemistry underlying such biologically important processes and hence has significance in deriving guidelines for rational drug design.

Organophosphine bearing multiple hydrogen-bond donors for asymmetric Michael addition reaction of 1-oxoindane-2-carboxylic acid ester via dual-reagent catalysis

Multiple hydrogen bonds containing nucleophilic phosphines derived from dipeptide dual-reagents catalyzed asymmetric Michael addition reactions between indene esters and activated olefins in high yields and good to excellent enantioselectivities under mild reaction conditions. The success of current highly selective reactions should provide inspiration for expansion to other reactions and would open up new paradigms for the synthesis of indanone derivatives bearing chiral quaternary carbon centers.

Extraction of activated epimedium glycosides in vivo and in vitro by using bifunctional-monomer chitosan magnetic molecularly imprinted polymers and identification by UPLC-Q-TOF-MS

In this work, efficient, sensitive bifunctional-monomer chitosan magnetic molecularly imprinted polymers (BCMMIPs) were fabricated and successfully applied to concentrate the metabolites of Epimedium flavonoids in rat testis and bone that were later analyzed using UPLC-Q-TOF-MS. Using chitosan and methacrylic acid as co-functional monomers, BCMMIPs exhibited a large adsorption capacity (7.60 mg/g), fast kinetics (60 min), and good selectivity. Chitosan is bio-compatible and non-toxic, and methacrylic acid provides multiple hydrogen bond donors. The BCMMIPs were injected into rat testis to specifically enrich the total flavonoid metabolites in vivo and were used to extract metabolites from bone in vitro. The results showed that the BCMMIPs coupled with UPLC-Q-TOF-MS successfully identified 28 compounds from testis and 18 compounds from bone, including 19 new compounds. This study provided a reliable protocol for the concentration of metabolites from complex biological samples, and several new metabolites of Epimedium flavonoids were found in vivo and in vitro.