Published papers

A new 15-membered-macrocyclic molecular entity, oxa-TriQuinoline (o-TQ), was designed and synthesized. In o-TQ, three oxygen atoms were joined onto three quinoline units at the 2- and 8-positions in a head-to-tail fashion by three-fold SNAr reactions, giving rise to the characteristic N3O3 aza-oxa-crown architecture. o-TQ can serve as a new tridentate nitrogen ligand to capture a CuI cation and adopt a bowl shape, before supramolecular complexation with corannulene and [12]cycloparaphenylene (CPP) occurs through π–π and CH–π interactions. In the presence of the CuI cation, the non-emissive o-TQ becomes a highly emissive material in the solid state, whereby the emission wavelengths depend on the ancillary ligand on the CuI cation. The o-TQ/CuI complex is able to promote carbene catalysis to provide a range of enamines with a gem-difluorinated terminus.

Chiral macrocycles are attracting growing interest due to their broad applicability as ligands in asymmetric catalysis and as host molecules for chiral recognition. Robustness and high thermodynamic stability can be effectively achieved by strategically linking aromatic panels to construct an axially chiral macrocyclic framework. Cyclic concatenation of four quinoline units affords a fully sp2-hybridized, non-planar macrocycle featuring four inwardly oriented, coordinatively active pyridyl nitrogen atoms. The previously reported tetramer TEtraQuinoline (TEQ) exhibits head-to-tail connectivity of its quinoline units, affording an achiral architecture possessing S4 symmetry. Herein, we report the design and synthesis of iso-TEtraQuinoline (i-TEQ), an inherently chiral analogue featuring head-to-head connectivity at the 2,2′- and 8,8′-positions, which gives rise to a D2-symmetric architecture. Detailed comparative investigations of the connectivity isomers i-TEQ and TEQ revealed an array of distinct characteristics, including the overall architecture, intrinsic macrocyclic strain, spatial orientation of nitrogen lone pairs, thermodynamic stability, racemisation behaviour, metal complex stability, and circularly polarised luminescence.

Macrocyclic compounds, exhibiting unique properties arising from their large-ring frameworks, have captivated the attention of organic chemists over the last few decades. These molecules serve specific functions across disciplines, including synthetic chemistry, materials science, and biology. Representative molecules in this category, including crown ethers, calix[n]arenes, and porphyrinoids composed of ether/phenol/pyrrole subunits, exhibit unparalleled structural and functional diversity. In contrast, macrocycles exploiting quinoline/quinazoline as key building blocks to construct specific macrocyclic architectures have received limited attention and are much less explored. In this Highlight Review, we summarize our recent advances in oligo-quinoline/quinazoline macrocycles. Emphasis is focused on synthetic strategies, structural features, and emerging applications in organometallic, supramolecular, and photophysical chemistry. We anticipate that these collective results will guide new molecular designs within the broader family of heterocycle-based macrocycles.

In the present study, we newly synthesized three types of novel fullerene derivatives: pyridinium-type derivatives trans-3a and 4a-5b, piperidinium-type derivative 9, and proline-type derivatives 10a-12. Among the assessed compounds, 5a, 10e, 10f, 10i, 11a-d, and 12 were found to inhibit both HIV reverse transcriptase and HIV protease (HIV-PR), with IC50 values in the low micromolar range being observed. Regarding HIV-PR inhibition activity, proline-type derivatives 11a-11d and 12, bearing an alkyl chain between the hydroxylmethylcarbonyl (HMC) moiety and pyrrolidine ring, were more potent than other derivatives. This result might indicate that connecting HMC moieties with proline-type fullerene derivatives through properly sized alkyl chain leads to improved HIV-PR inhibitory activity.

In the present study, we newly synthesized four types of novel fullerene derivatives: pyridinium/ethyl ester-type derivatives 3b−3l, pyridinium/carboxylic acid-type derivatives 4a, 4e, 4f, pyridinium/amide-type derivative 5a, and pyridinium/2-morpholinone-type derivative 6a. Among the assessed compounds, cis-3c, cis-3d, trans-3e, trans-3h, cis-3l, cis-4e, cis-4f, trans-4f, and cis-5a were found to inhibit HIV-1 reverse transcriptase (HIV-RT), HIV-1 protease (HIV-PR), and HCV NS5B polymerase (HCV NS5B), with IC50 values observed in the micromolar range. Cellular uptake of pyridinium/ethyl ester-type derivatives was higher than that of corresponding pyridinium/carboxylic acid-type derivatives and pyridinium/amide-type derivatives. This result might indicate that pyridinium/ethyl ester-type derivatives are expected to be lead compounds for multitargeting drugs to treat HIV/HCV coinfection.

Oxa-TriQuinoline (o-TQ) is a new entry in the collection of aza-oxa-crown compounds featuring a semi-rigid flexible conformation and a tripodal ligation capability through three quinoline units. Herein, we describe the installation of functional groups and aromatic substituents on the outer edge of o-TQ to modulate its physicochemical properties. Amino and bromo substituents were regioselectively introduced at the 5-position, forming bowl-shaped Cu(I) complexes in which three quinoline units coordinated to Cu(I). X-ray crystallography indicated that these o-TQ derivatives preferred an almost identical geometry in both the absence and presence of Cu(I). In contrast to o-TQ, some new o-TQ derivatives exhibited photoluminescent properties in solution and/or in the solid state depending on the substituents.

A new family of 16-membered macrocycles comprising two indole (In) and two quinoline (Q) units, coined In2Q2, was synthesized. Each unit is diagonally located and concatenated in a head-to-tail fashion, furnishing a non-flat saddle-shaped architecture with C2 symmetry. The synthetic protocol utilizing macrocyclic diamide as a pivotal precursor allowed us to access a series of In2Q2 derivatives bearing various substituents on the periphery. The In2Q2 derivatives and their Zn2+ complexes were emissive in both solution phase and solid state. While the entire architecture of In2Q2 is similar to that of quinoline tetramer TEtraQuinoline, a couple of contrasting physicochemical properties were revealed.

Macrocyclic compounds exhibit unique properties due to their large ring─shaped structures, which have captivated chemists in recent decades. These molecules exert specific functions in a multidisciplinary basis, e.g. chemistry, materials science, and biology. Crown ethers, calix [n] arenes, and porphyrinoids, which contain several ether／phenol／pyrrole subunits, represent milestones in these molecular categories with unparalleled functional diversity. In contrast, macrocycles exploiting quinoline as a key unitary element to construct specific macrocyclic architecture have received limited attention and been barely explored. In this report, we summarize the recent advances in oligo─ quinoline macrocycles TriQuinoline (TQ), oxa─TriQuinoline (o─TQ), TEtraQuinoline (TEQ), and indole／quinoline hybrid macrocycle In2Q2. Particular emphasis is placed on the synthesis, structure, and application of these molecules in organometallic and supramolecular chemistry, which may guide new molecular designs in the heterocycle─based macrocycle family.

TriQuinoline (TQ), a quasi-planar cyclic quinoline trimer concatenated at the 2,8-positions in a head-to-tail arrangement, strongly captures a proton at the 12-membered inner cycle and exhibits unusual physicochemical properties, including unexpected water solubility and the ability to engage in complexation with other π-conjugated molecules. In this study, we designed and synthesized its expanded analog, coined Enlarged-TriQuinoline (Enl-TQ), in which three alkyne units are embedded between three quinoline units to acquire an expanded planar 18-membered ring system. DFT calculations and X-ray crystallographic analysis revealed its planar architecture with three inwardly facing pyridinic nitrogen atoms. Despite its structural similarity to TQ, Enl-TQ displayed distinct host capability and photophysical characteristics.