Hak-Fun Chow

Facile Assembly of Chiral Metallosquares by Using Enantiopure Tribenzotriquinacene Corner Motifs

A pair of enantiomerically pure metallosquares based on linear platinum-diacetylene edges and tribenzotriquinacene corner units was synthesized. Their structures were characterized by (1) H-, (13) C- and (31) P NMR spectroscopy as well as MALDI-TOF mass spectrometry and circular dichroism. Based on DFT calculation, the optimized geometry possesses a distorted square conformation in which the four edges are not sitting on the same plane. The molecular square further self-assembled in the solid state to afford microspheres with diameter of approximately 300 nm, as determined by scanning electron microscopy.

Regiocontrolled synthesis and optical resolution of mono-, di-, and trisubstituted tribenzotriquinacene derivatives: key building blocks for further assembly into molecular squares and cubes.

The regiocontrolled syntheses of four chiral C1- or C3-symmetrical tribenzotriquinacene (TBTQ) derivatives bearing methoxy or hydroxy groups at the peripheral positions [(2,6-(OMe)2, (±)-18 and (±)-20; 2,6-(OH)2, (±)-19; and 2,6,10-(OMe)3, (±)-21] by two different synthesis protocols are reported. Compounds (±)-19, (±)-20, and (±)-21 and two (already-known) monosubstituted C1-symmetrical TBTQ analogues [2-OH (±)-23 and 2-OMe (±)-24] were readily resolved by chiral HPLC, and their absolute configurations were determined by X-ray crystallography and/or circular dichroism (CD) studies. Optical resolution of three closely related TBTQ derivatives [2,6-(OMe)2, (±)-18; 2-OMe, (±)-22; and 2-OH, (±)-25] containing the same peripheral substituents but other bridgehead residues failed. Enantiopure TBTQ derivatives of this sort are considered promising structural motifs toward the construction of molecular squares and cubes.

Electronic and steric effects on the three-fold Scholl-type cycloheptatriene ring formation around a tribenzotriquinacene core

Systematic studies on the role of substituents in the bay-bridging cycloheptatriene ring formation around the tribenzotriquinacene (TBTQ) core via the non-typical Scholl reaction were carried out. The electronic effect of the substituents was found to be the predominant factor that controls the ease of the cyclization reaction, while the steric effect of methoxy groups in the bay regions of the TBTQ core appears to be also significant but less important. In several cases with insufficient electronic activation and/or unfavorable steric restriction, single bay-bridging occurred with or without concomitant bridgehead hydroxylation. Alternatively, an unprecedented ring opening/closure of the TBTQ skeleton by electrophilic ipso-attack was found to intervene in other cases. Starting from the electronically and sterically most favorable precursor, a 1,4,8-tris-(2,3,4-trimethoxyphenyl)-TBTQ derivative, a new wizard-hat-shaped, three-fold bay-bridged TBTQ nanographene core bearing nine methoxy groups at the molecular periphery was synthesized with high efficiency.

From Fenestrindane towards Saddle-Shaped Nanographenes Bearing a Tetracoordinate Carbon Atom

Two saddle-shaped polycyclic aromatic compounds (8 a and 8 b) bearing an all-cis-[5.5.5.5]fenestrane core surrounded by an o,p,o,p,o,p,o,p-cyclooctaphenylene belt were synthesized and characterized by NMR spectroscopy and mass spectrometry. The key step of this synthesis involves the formation of four cycloheptatriene rings from the corresponding electron-rich 1,4,9,12-tetraarylfenestrindane derivatives 7 a and 7 b in Scholl-type cyclizations. The structural details of the D2d -symmetric saddle compound 8 a were determined by X-ray crystallography, and the properties of 8 a and 8 b were studied by UV/Vis and fluorescence spectroscopy and cyclic voltammetry.

Transition from low molecular weight non-gelating oligo(amide-triazole)s to a restorable, halide-responsive poly(amide-triazole) supramolecular gel

A self-assembled poly(amide-triazole) physical gel (1) was found to show responsive behaviour towards halide anions, while the corresponding monomeric (2) and dimeric homologues (3) were non-gelating. In the presence of halide anions, polymer gel 1 collapsed to become a solution, but could be restored back to the gel state after addition of a AgNO3 salt.

Synthesis and Thermoreversible Gelation Properties of Main-Chain Poly(pyridine-2,6-dicarboxamide-triazole)s

A series of main-chain poly(amide-triazole)s were prepared by copper(I)-catalyzed alkyne-azide AABB-type copolymerizatons between five structurally similar diacetylenes 1-5 with the same diazide 6. The acetylene units in monomers 1-5 possessed different degrees of conformational flexibility due to the different number of intramolecular hydrogen bonds built inside the monomer architecture. Our study showed that the conformational freedom of the monomer had a profound effect on the polymerization efficiency and the thermoreversible gelation properties of the resulting copolymers. Among all five diacetylene monomers, only the one, that is, 1-Py(NH)(2) which possesses the pyridine-2,6-dicarboxamide unit with two built-in intramolecular H bonds could produce the corresponding poly(amide-triazole) Poly-(PyNH)(2) with a significantly higher degree of polymerization (DP) than other monomers with a lesser number of intramolecular H bonds. In addition, it was found that only this polymer exhibited excellent thermoreversible gelation ability in aromatic solvents. A self-assembling model of the organogelating polymer Poly-(PyNH)(2) was proposed based on FTIR spectroscopy, XRD, and SEM analyses, in which H bonding, π-π aromatic stacking, hydrophobic interactions, and the structural rigidity of the polymer backbone were identified as the main driving forces for the polymer self-assembly process.

Tribenzotriquinacene-Based Crown Ethers: Synthesis and Selective Complexation with Ammonium Salts.

Two tribenzotriquinacene-based crown ethers, TBTQ-dibenzo-24-crown-8 5 and TBTQ-benzo-21-crown-7 6, were prepared from the key TBTQ intermediate, 2,3-dihydroxy-4b,8b,12b,12d-tetramethyltribenzotriquinacene (13), which in turn was synthesized in six steps using two variants of our cyclodehydration method on a multigram scale. The host-guest complexation properties of the TBTQ-based crown ethers 5 and 6 with a paraquat derivative, 16, and two secondary ammonium salts, 17 and 18, were studied by 1H NMR spectroscopy and mass spectrometry. It was found that host 5 binds to the paraquat derivative 16 as a 1:1 complex in CDCl3/CD3CN solution with an association constant of Ka = (9.2 ± 1.8) × 102 M-1, whereas no complexation was found for 17 and 18. In contrast, the TBTQ-crown ether 6 assembles selectively with dibutylammonium hexafluorophosphate 18 as a 1:1 complex in CDCl3/CD3COCD3 [Ka = (5.0 ± 1.4) × 102 M-1], for which a threaded [2]pseudorotaxane structure is assumed.

Different Gelation and Self‐Sorting Properties of Two Isomeric Polyamides Owing to the Parallel versus Anti‐Parallel Alignment of Backbone Dipoles

Two isomeric bottlebrush polyamides P-1 and A-1, with the same repeating monomer dipole units aligned along the polymer backbone in pseudo-parallel and pseudo-antiparallel fashion, respectively, were synthesized and characterized. Both polymers can form thermoreversible gels with aromatic solvents but P-1 was found to show inferior gelation strength compared with that of A-1. Furthermore, despite their close structural resemblance, a 1:1 mixture of the P-1 and A-1 polymers was shown to exhibit self-sorting in the gel state. Gel formation was found to be a kinetically trapped process through hydrogen bonding, π-π stacking interactions, and side chain interdigitation. The different gelation and self-sorting properties can be explained by the local dipole-dipole interactions originating from the different modes of backbone dipole alignment. In single gel systems, the antiparallel-aligned dipoles in A-1 facilitated a more compact molecular packing owing to the enthalpically more favorable polymer chain association. On the other hand, the parallel-aligned dipoles in P-1 gave rise to a less stable head-to-head packing, which had difficulties to convert to the more stable head-to-tail packing in a kinetically trapped environment. In the mixed gel system, it is the unfavorable hetero-polymer mismatch dipole-dipole interaction that inhibited the mixing of the A-1 and P-1 polymers and led to self-sorting.

Identification of influenza polymerase inhibitors targeting polymerase PB2 cap-binding domain through virtual screening

Abstract Influenza A virus is the major cause of epidemics and pandemics worldwide. In this study, virtual screening was used to identify compounds interacting with influenza A polymerase PB2 cap‐binding domain (CBD). With a database of 21,351 small molecules, 28 candidate compounds were tested and one compound (225) was identified as hit compound. Compound 225 and three of its analogs (225D1, 426 and 426Br) were found to bind directly to PB2 CBD by surface plasmon resonance (SPR). The evaluation of compounds 426Br and 225 indicated that they could bind to PB2 CBD and inhibit influenza virus at low micromolar concentration. They were predicted to bind the cap binding site of the protein by molecular modeling and were confirmed by SPR assay using PB2 CBD mutants. These two compounds have novel scaffolds and could be further developed into lead compound for influenza virus inhibition. HighlightsWe have developed a screening protocol to obtain PB2 cap‐binding protein compounds from a virtual database.Several novel compounds were identified to inhibit RNP activity and suppress influenza virus replication.Structure activity relationships among the hit compounds were investigated.