Aromatic oligoureas composed of meta-linked residues bearing phenolic ether side chains are synthesized. The basic N,N′-diarylurea units adopt a trans,trans intramolecularly H-bonded conformation that is further strengthened by additional intermolecular H-bonding. Such basic units, in combination with meta-linked benzene residues, result in stably folded helical oligoureas in the highly polar DMF with up to four turns and with a small cylindrical inner pore that would be difficult to acquire.

Four [12]aneN3 modified tetraphenylethene (TPE) compounds with different numbers of polyamine units and structure configurations, namely 1, 2, 3, and 4, were designed and synthesized. All compounds showed strong aggregation-induced emission (AIE) features. Compounds 2 and 4 showed significant emission enhancement after the addition of ssDNAs and dsDNAs of different lengths as well as calf thymus DNA (ctDNA). Compounds 1 and 3 showed very poor fluorescent responses toward DNAs. Gel electrophoresis demonstrated the abilities of 1–4 to condense DNA effectively. Complete retardation of plasmid DNA can be achieved at a concentration of 25 μM (1), 8 μM (for 2 and 3) and 4 μM (4). Experiments including fluorescent contrastive titrations, scanning electron microscopy, dynamic laser scattering, EB displacement, and gel electrophoresis demonstrated that the four compounds were able to integrate with DNA through electrostatic interactions and supramolecular stacking. A vicinal configuration around TPE (2) and more triazole-[12]aneN3 recognition sites (4) evidently enhanced the sensing capability toward oligonucleotides, and the TPE unit played an important role in the plasmid DNA condensation process because of its strong binding. With the advantages of low cytotoxicity, effective DNA sensing, and DNA condensing properties, compound 4 was successfully applied as a nonviral DNA vector and fluorescent tracer for label-free gene delivery, which is the first example of a nonviral gene vector with AIE activity.Keywords: aggregation-induced emission; cytotoxicity; DNA condensation; nonviral gene vector; nucleic acid sensing; [12]aneN3;

Four gemini amphiphiles decorated with triazole–[12]aneN3 as the hydrophilic moiety and various long hydrocarbons as hydrophobic moieties, 1–4, were designed to form micelles possessing the aggregation-induced emission (AIE) property for gene delivery and tracing. All four amphiphiles give ultralow critical micelle concentrations, are pH-/photostable and biocompatible, and completely retard the migration of plasmid DNAs at low concentrations. The DNA-binding abilities of the micelles were fully assessed. The coaggregated nanoparticles of 1–4 with DNAs could convert back into AIE micelles. In vitro transfections indicated that lipids 1 and 2 and their originated liposomes bearing decent delivering abilities have great potentials as nonviral vectors. Finally, on the basis of the transfection and the transitions between condensates and micelles, lipid 2 was singled out as the first example for real-time tracing of the intracellular deliveries of nonlabeled DNA, which provides spatiotemporal messages about the processes of condensate uptake and DNA release.Keywords: AIE micelles; gemini lipids; gene delivery tracing; micelle and nanoparticle transition; nonviral gene vectors;

A rationally designed amphiphile containing a hydrophobic Hantzsch ester and a hydrophilic phosphate ester was able to form vesicles in aqueous solution, and resulted in the first example of a NO-responsive drug delivery system.

Six oligoamides with the same backbone but different side and end chains, G1–G6, were designed and synthesized. Screening the gelating abilities of these oligoamides revealed G2 as a versatile gelator capable of forming stable hydrogels as well as several organogels. From UV, fluorescence, NMR, and SEM studies, the formation of hydrogels is driven by hydrophobic forces and π–π stacking while the gelation of nonpolar organic solvents relies on hydrogen-bonding interactions. The hydrogel of G2 is able to encapsulate and release medicinally important polar substances into water with acid-responsiveness.

Degradable polymers as gene and drug carriers are emerging as one of the most promising types of materials in the biomedical and pharmaceutical areas. Herein, we report the synthesis of a series of block co-polyesters (B1–B6) and random co-polyesters (C1–C4) via ring-opening polymerization of tertiary amine-bearing valerolactone and alkylated valerolactone monomers. These polymers can completely inhibit the electrophoretic migrations of plasmid DNAs (pDNAs) at a w/w ratio of 2–6. The polyplexes of these polymers with pDNAs were steadily formed in a narrow range of sizes (75 to 220 nm) and could be effectively internalized into the cytoplasm. The results of transfection experiments showed that the block copolymers generally exhibited better performance than their random counterparts and the aliphatic chain lengths on the backbone of the polymers obviously affected the transfection efficiency (TE). Block copolymer B5 with n-octyl chains generated the best TE in Hek293T cells, which was 2.2 fold that of polyethylenimine (PEI) 25k under the optimal conditions. Moreover, these polymers were found to be more biocompatible compared to PEI 25k, and showed degradable properties. Our results suggest that these polymers are potentially reliable/efficient non-viral gene vectors.

Rigid macrocycles 2, which share a hybrid backbone and the same set of side chains while having inner cavities with different inward-pointing functional groups, undergo similar nanotubular assembly as indicated by multiple techniques including 1H NMR, fluorescence spectroscopy, and atomic force microscopy. The formation of tubular assemblies containing subnanometer pores is also attested by the different transmembrane ion-transport behavior observed for these macrocycles. Vesicle-based stopped-flow kinetic assay and single-channel electrophysiology with planar lipid bilayers show that the presence of an inward-pointing functional (X) group in the inner cavity of a macrocyclic building block exerts a major influence on the transmembrane ion-transporting preference of the corresponding self-assembling pore. Self-assembling pores with inward-pointing amino and methyl groups possess the surprising and remarkable capability of rejecting protons but are conducive to transporting larger ions. The inward-pointing groups also resulted in transmembrane pores with a different extent of positive electrostatic potentials, leading to channels having different preferences for transporting chloride ion. Results from this work demonstrate that synthetic modification at the molecular level can profoundly impact the property of otherwise structurally persistent supramolecular assemblies, with both expected tunability and suprisingly unusual behavior.

Three novel D–A–D type chromophores, consisting of substituted triphenylamine and aggregation-induced emission (AIE)-active tetraphenylethylene moieties, 1 (with two ethoxy groups), 2 (with two hydroxyl groups), 3 (non-substituted), were synthesized and characterized. Their one-photon excited fluorescence (OPEF) quantum yields (ΦF) and lifetimes (τ) in organic solutions increased with the increase of the electron-donating ability of the substituents on the triphenylamine unit, i.e., 1 > 2 > 3. By means of dynamic light scattering and scanning electron microscopy, it was found that the higher hydrophobicity of 1 resulted in larger particle sizes and a strong AIE effect. 1 and 2 showed good two-photon excited fluorescence (TPEF) and two-photon absorption cross-sections (σ) (4230 and 4004, respectively) and proved to have good biocompatibility. Both compounds 1 and 2 were successfully applied in cell imaging based on their OPEF and TPEF properties. This work clearly implies that these chromophores can be finely tuned for different optical properties and applications through varying the electron-donating ability, hydrophobicity, and cytotoxicity of the substituents.

Aromatic oligoureas 3 and 4 have urea moieties engaging in weak intramolecular H-bonding that constrains their backbones. The shorter 3a and 3b are able to bind chloride and acetate but not their corresponding counterion. The longer 4 binds both an anion and its counterion with the same affinity.

Small organic non-viral gene vectors with the structural combinations of (aliphatic chain)–naphthalimide–[12]aneN3 (11a, b) and naphthalimide–(aliphatic chain)–[12]aneN3 (12a–c) were synthesized and fully characterized. Agarose gel electrophoresis experiments indicated that the first type of compounds, 11a and 11b, could completely retard DNA at the concentration of 5 μM in the presence of DOPE. Within the second type of compounds, 12c with the decane chain showed a complete retardation of DNA at the concentration of 20 μM, whereas 12a and 12b with the ethyl and hexyl chains could not retard DNA effectively. Dynamic light scattering measurements indicated that compounds 11a, 11b and 12b, 12c condensed DNA into nanoparticles with the size in the range of 60–160 nm. Due to the strong fluorescence of 11a and 11b, the distribution of lipids/DNA complexes and the process of DNA release from the lipids were clearly observed via cellular uptake experiments. On the other hand, the non-fluorescent 12a–c enabled the EB exclusion assay to afford the binding constants of 4.88 × 106 M−1 (12a), 4.18 × 106 M−1 (12b) and 3.39 × 106 M−1 (12c), respectively. The MTT assay revealed that both types of compounds have low cytotoxicity. Non-fluorescent 12c was successfully applied in the eGFP expression experiments in A549 cells and showed stronger green fluorescence emission than that of lipofectamine 2000. Quantitative transfection experiments through the luciferase assay further revealed that compounds 11a, 11b and 12c can act as non-viral gene vectors in different cell lines. Among them, 12c gave the highest transfection efficiency in HeLa cells, which was about 2 times that offered by lipofectamine 2000. This work clearly demonstrated that the right combination of different functional units and long aliphatic linkers will likely promote gene delivery and transfection efficiency.

Two fluorescent probes, 1 and 2, derived from borondipyrromethene (BODIPY) modified with macrocyclic polyamine [12]aneN3, were synthesized and applied in the discrimination of cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) with absorption and fluorescent spectroscopy in comparison. It was found that Boc-protected 1 showed highly sensitive and selective recognition of GSH over Cys and Hcy; while probe 2 was able to distinguish the three different thiols due to their different reactivities. With its water-solubility, rapid responsiveness, high sensitivity and low cytotoxicity, probe 2 was successfully applied in the fast detection of three biothiols in living cells.

A macrocyclic polyamine lipid bearing both fluorescent naphthalimide and targeting cholic acid moieties, 1, was designed and synthesized as a novel non-viral gene vector. Plasmid DNA was completely condensed at 10 μM of 1 (N/P = 3.6) in 5 minutes at 37 °C. The process of DNA uptake process by 1 in a single cell was clearly investigated through time-dependent fluorescence microscopy assay. Flow cytometry experiments of liposome 1 clearly proved its targeting activity toward HepG2 cells. Luciferase gene expression transfected by the DNA complex of 1/DOPE gave a higher transfection efficiency in HepG2, A549, HeLa, U2OS and CCC-HPF-1 cells than by lipofectamine 2000. The present work demonstrated that the designed multifunctional organic molecule is able to fluorescently track the gene delivery process at a single-cell level for the first time. This will greatly aid mechanistic studies of gene transfection and further development of new gene vectors for biomedical applications.

•1 showed excellent ability in the sequential detection of Cu2+ ions and ATP.•The recognition mechanism was explored in detail.•1-Cu complex was able to sensitively monitor ATP change in living cells.A new fluorescent probe 1 featuring one 1,8-naphthalimide and two [12]aneN3 units was synthesized. In the presence of Cu2+ ions, the fluorescence emission of 1 was quenched by a factor of 127-fold and no interference by other metal ions was observed under physiological conditions. By means of titration and a Job's plot it was established that 1 forms a complex with Cu2+ ions in a 1:2 ratio. The fluorescence of the 1-Cu2+ complex was recovered by the addition of Adenosine-5′-triphosphate (ATP) in aqueous solution. Due to its low cytotoxicity, good water solubility, and high sensitivity, probe 1 was successfully applied in the sequential recognition of Cu2+ and ATP in aqueous solution and HeLa cells. The highly selective and sensitive ability of 1-Cu2+ complex to detect ATP even enables its bio-analytical applications in real-time imaging in living cells.A new water soluble fluorescent probe 1 with lower cell toxicity was successfully applied in the sequential recognition of Cu2+ ions and ATP in aqueous solution and in living cells.

•DHPS showed sensitively and selectively fluorescent detection of NO in water, the limitation of the detection is 18 nM.•The NO-induced aromatization of dihydropyridine in DHPS is responsible for the fluorescent switch-on mechanism.•The probe was successfully applied in the field of cell imaging for detecting the endogenously generated NO.A water soluble Hantzsch ester derivative of coumarin, DHPS, was synthesized and successfully applied in the fluorescent sensing nitric oxide (NO) in aqueous solution. The fluorescence of probe DHPS is extremely weak, while its fluorescence was greatly switched on upon the addition of NO solution and showed high selectivity and sensitivity to NO. The limitation of the detection was calculated to be 18 nM. The NO-induced aromatization of dihydropyridine in DHPS to pyridine derivative (PYS) proved to be the switching mechanism for the fluorescent sensing process, which was confirmed through spectra characterization and computation study. Cytotoxicity assay demonstrated both DHPS and PYS are biocompatible, the DHPS was successfully applied to track the endogenously produced NO in the RAW 264.7 cells.

A series of bifunctional molecules with different combinations of macrocyclic polyamine [12]aneN3 and coumarin moieties, 4a/b and 5a/b, were synthesized by a two-step copper(I)-mediated alkyne–azide click reactions between 1,3,5-tris(azidomethyl)benzene and Boc-protected N-propynyl-[12]aneN3/7-propynyloxycoumarins. Agarose gel electrophoresis experiments indicated that bifunctional molecules 4b and 5b effectively induced complete plasmid DNA condensation at concentrations up to 40 μM. It was found that the structural variation had a major impact on the condensation behavior of these compounds. The electrostatic interaction involving the [12]aneN3 moiety can be compensated by the binding contribution of the coumarin units during the DNA condensation process. These two types of interaction showed different effects on the reversibility of DNA condensation. Results from studies using dynamic laser scattering, atomic force microscopy, and EB replacement assay further supported the above conclusion. Cytotoxicity assays on bifunctional compounds 4a/b and 5a/b indicated their low cytotoxicity. Results from cellular uptake and cell transfection experiments proved that bifunctional compounds 4b and 5b successfully served as non-viral gene vectors. Furthermore, methyl substituents attached to the coumarin unit (4b and 5b) greatly enhanced their DNA condensation capability and gene transfection. These bifunctional molecules, with the advantages of lower cytotoxicity, good water solubility, and potential structural modification, will have great potential for the development of new non-viral gene delivery agents.

Bifunctional molecules containing macrocyclic polyamine [12]aneN3 and carbazol units, 1–4, have been efficiently synthesized and fully characterized. Through gel electrophoresis, atomic force microscopy, and dynamic light scattering experiments, compounds 3 and 4b bearing both [12]aneN3 and carbazol moieties showed effective DNA condensation ability at the concentration of 80 μM. Investigations from EB displacement fluorescence spectra, viscosity titration, and ionic strength effects revealed that the effective DNA condensation comes from the appropriate combination of carbazol and [12]aneN3 units in the bifunctional molecules, and the DNA condensation process is reversible. The incorporation of triazole units in the molecules clearly reduced the cytotoxicity.

•New palladacycles have been synthesized and immobilized on silica gel.•New palladacycles are catalytically effective in the methanolysis of pesticides.•Immobilized palladacycle catalysts are reusable and high efficient.New oxime-derived palladacycles were prepared, spectral characterized, and immobilized on silica gel. Homogeneous catalysis indicates that pyridine coordinated oxime-derived palladacycles 1 and 2 were very effective in the methanolysis of fenitrothion, but suffered from the formation of the inactive dimmer at higher concentration. Immobilization of oxime-derived chloro-coordinated mononuclear and chloro-bridged dinuclear palladacycles afforded the high efficient and recoverable heterogeneous catalysts Si–Pd1 and Si–Pd2, both solid catalysts proved to be reusable in 10 runs and fascinated the degradation of a series of phosphorothionate pesticides up to 4.9 × 108 folds at sspH 8.8 and 25 °C.Immobilization of oxime-derived palladacycles afforded the high efficient and reusable heterogeneous catalysts for the degradation of a series of phosphorothionate pesticides.

N-Amidothioureas bearing nitro groups showed different sensitivities to various anions, while those with methoxy moieties exhibited the sensitive and selective fluorescence turn-on property for Zn2+ in aqueous solution and in cells. N-Amidothioureas can therefore be adjusted from anion-selective sensors to Zn2+-selective sensors by varying the electronic effects of their substituents.

A series of N-methylated mono- and di-[12]aneN3 ligands (5–9) have been synthesized and characterized. The steric effects on the catalytic activities of their mononuclear and dinuclear zinc(II) complexes in the cleavage of a RNA model 2-hydroxypropyl 4-nitrophenyl phosphate (HPNPP, 3) and a DNA model methyl 4-nitrophenyl phosphates (MPNPP, 4) in methanol have been investigated at 25 °C. In the cleavage of phosphate 3 catalyzed by the mononuclear complexes, derived from the N-methylation in the [12]aneN3 backbone, the plots of kobsversus [Zn(II)] changed from an upward curvature to linearity with increasing level of methylation, indicating that N-methylations led to a reduction of dinuclear association that was responsible for the synergetic effect. Compared to the activities of the complex with non-methylated di-[12]aneN3 ligand, those of the dinuclear zinc(II) complex (Zn2-8), which has the two N-methyl groups, were reduced by two orders of magnitude as measured by the second-order rate constants and synergetic effect in the cleavage of both model compounds. For reactions catalyzed by the fully N-methylated dinuclear complex (Zn2-9), no synergetic effect was observed. Nevertheless, complex Zn2-8 still showed the remarkable catalytic efficiency, with rate accelerations of 109–10-fold in the cleavage of each of the two phosphates relative to the background reactions, and the synergetic effects of up to 561 folds. pH jump experiments confirmed that the rate-limiting step in the cleavage of 3 by Zn2-8 involved the binding process, while that in the reaction with 4 was the chemical cleavage of the P–O bond. Steric effects in the cleavage reactions were analyzed in detail and were compared with the electronic effect caused by oxy anion bridging group in the di-[12]aneN3 ligand and also with the hydrophobic effect observed in other systems. The work has further confirmed that the combination of the cooperativity between two metal ions and a medium effect could result in excellent catalytic activities for the cleavage of phosphate diesters.

In this Letter, a series of macrocyclic polyamine [12]aneN3–dipeptide conjugates as a new type of metal-free nucleases were synthesized and fully characterized with 1H NMR, 13C NMR, IR, and HR-MS. Results indicate that these conjugates can bind to calf thymus DNA mainly through electrostatic interaction and can cleave the plasmid DNA at 200 μM (pH 7.2, 37 °C), with an acceleration of 106-fold via hydrolytic pathway.

Oxime-derived palladacycles were successfully applied as a novel class of catalysts in the intramolecular Pauson–Khand reactions. Allylpropargyl ethers and allylpropargyl amines can be efficiently converted to the cyclopentenone products with good to excellent yields.

A new [12]aneN3-based fluorescent sensor 3 has been efficiently synthesized through click chemistry. This sensor demonstrates high selectivity for Zn(II) ions in aqueous solution at pH 7.2, even in the presence of other competitive cations.A new [12]aneN3-based fluorescent sensor 3 showed high selectivity for Zn(II) in the presence of other competitive cations in aqueous solution at pH 7.2.Highlights► A new [12]aneN3-based sensor has been synthesized through click reaction. ► The sensor has showed high selectivity for Zn(II) in aqueous solution at pH 7.2. ► The work proves that [12]aneN3 can be a good acceptor in chemical sensors.

A series of mono- and di-[12]aneN3 ligands 1–6, which contain different substituents on the coordinating backbone, different linkers between two [12]aneN3 units and different N-methylation on the [12]aneN3 units, have been synthesized and fully characterized. The catalytic activities of their metal complexes on the cleavage of RNA model phosphate 2-hydroxypropyl-p-nitrophenyl phosphate (HPNPP) varied with the structures of the ligands and metal ions. Click reactions afforded an efficient method to prepare a series of [12]aneN3 ligands, however, the incorporation of triazole moieties reduced the catalytic activities due to their coordination with metal ions and the strong inhibition from the triflate counter ion. Dinuclear zinc(II) complexes containing an m-xylyl bridge showed higher catalytic activities with synergistic effects up to 700-fold. Copper(II) complexes with the ligands without triazole moieties proved to be highly reactive and showed strong cooperativity between the two copper(II) ions. In terms of k2, dinuclear complexes Zn2-3b, Zn2-3d, Zn2-4b, and Cu2-4b afforded activities of 7.9 × 105, 3.9 × 104, 9.0 × 104, and 8.1 × 104-fold higher than that of methoxide. The ortho arrangement of the two [12]aneN3 units and the presence of 5- or 2-positioned substituents in the benzene ring as well as N-methylation of [12]aneN3 units greatly reduced the catalytic activities due to the steric effects. These results clearly indicate that the structures of the linker between two [12]aneN3 units play very important role in their catalytic synergistic effects.

Mono-, di-, and tri-nucleating [12]aneN3 ligands 3–5 have been efficiently prepared through the copper-mediated click reactions between propargyl modified [12]aneN32 and mono-, bis-, and tri-azido compounds. Their corresponding zinc(II) and copper(II) complexes showed excellent catalytic activity and strong synergetic effects in the cleavage of RNA model phosphate diester.Mono-, di-, and tri-nuclear complexes containing [12]aneN3 ligating units have been efficiently prepared through click reactions and showed excellent catalytic activity and strong synergetic effects in the cleavage of RNA model phosphate diester.

Mononuclear and dinuclear palladacycles derived from 1,3-bis(N,N-dimethylaminomethyl)benzenes, [{Pd(Cl)}2,6-(Me2NCH2)2C6H3] (1) and [1-{Pd(H2O)(Py)}-5-{Pd(OTf)(Py)-2,4-(Me2NCH2)2C6H2]-(OTf) (2), were synthesized and their structures were fully characterized. Complex 1 is a pincer complex with η3-mer NCN phenyl backbone, complex 2 is a bispalladium(II) complex with 1,2- and 4,5- two C,N-ortho phenyl backbone. Whereas the pincer complex 1 acted as a poor catalyst on methanolysis of fenitrothion, complex 2 demonstrated high catalytic activity in the same reactions, but there is no synergetic effect between two palladium ions. The results clearly indicate that a dissociable co-ligand in the palladacycle compounds significantly promotes the catalytic methanolysis.Two palladacycles derived from 1,3-bis(N,N-dimehylaminomethyl)benzenes showed different coordination modes and different catalytic activity in the methanolysis of fenitrothion.

Cyclopalladated complexes with a N,N-dimethylaminomethylferrocenyl (dmaf) backbone and three pyridine co-ligands, [Pd{(η5-C5H5)Fe[(η5-C5H3)CH2NMe2]}Cl(R-Py)] (2: R = 4-H; 3: R = 4-cyano; 4: 4-N,N-dimethylamino) have been synthesized and characterized. The single crystal X-ray diffraction analyses show that the palladium(II) in both 3 or 4 is coordinated in a distorted square planar geometry with the two nitrogen atoms trans to each other. The three palladacyles were shown to greatly catalyze the methanolysis of the PS containing pesticide parathion but showed different accelerations. It was found that the replacement of phenyl by ferrocenyl in the palladacycle backbone of 2 lowers the kinetic pKass of the Pd-(HOCH3) required for activity by almost 2 units.Palladacycles 2–4 containing the N,N-dimethylaminomethylferrocenyl backbone and three pyridine co-ligands have been prepared and structurally characterized. Their catalytic activities in promoting the methanolysis of the pesticide parathion were investigated.

Two pyridine coordinated cyclopalladated complexes: (S)-chloro{2-[2-(4-iso-propyl)oxazolinyl]phenyl-C,N}(4-R-pyridine)palladium(II) (R = H, 1, R = NMe2, 2), have been synthesized and structurally characterized. Both complexes show that the palladium atom displays the expected square planar coordination with the pyridine and oxazoline nitrogen atoms positioned trans to one another. These two palladacycles can effectively catalyze the methanolysis of pesticide fenitrothion with an acceleration above 106–107 folds compared to that of the methoxide-catalyzed background reaction at pHss values of 10.80 and room temperature.Two palladacycle compounds with chiral oxazoline backbone (1 and 2), which were synthesized and structurally characterized, showed high catalytic activity in the methanolysis of pesticide.

A series of N-methylated mono- and di-[12]aneN3 ligands (5–9) have been synthesized and characterized. The steric effects on the catalytic activities of their mononuclear and dinuclear zinc(II) complexes in the cleavage of a RNA model 2-hydroxypropyl 4-nitrophenyl phosphate (HPNPP, 3) and a DNA model methyl 4-nitrophenyl phosphates (MPNPP, 4) in methanol have been investigated at 25 °C. In the cleavage of phosphate 3 catalyzed by the mononuclear complexes, derived from the N-methylation in the [12]aneN3 backbone, the plots of kobsversus [Zn(II)] changed from an upward curvature to linearity with increasing level of methylation, indicating that N-methylations led to a reduction of dinuclear association that was responsible for the synergetic effect. Compared to the activities of the complex with non-methylated di-[12]aneN3 ligand, those of the dinuclear zinc(II) complex (Zn2-8), which has the two N-methyl groups, were reduced by two orders of magnitude as measured by the second-order rate constants and synergetic effect in the cleavage of both model compounds. For reactions catalyzed by the fully N-methylated dinuclear complex (Zn2-9), no synergetic effect was observed. Nevertheless, complex Zn2-8 still showed the remarkable catalytic efficiency, with rate accelerations of 109–10-fold in the cleavage of each of the two phosphates relative to the background reactions, and the synergetic effects of up to 561 folds. pH jump experiments confirmed that the rate-limiting step in the cleavage of 3 by Zn2-8 involved the binding process, while that in the reaction with 4 was the chemical cleavage of the P–O bond. Steric effects in the cleavage reactions were analyzed in detail and were compared with the electronic effect caused by oxy anion bridging group in the di-[12]aneN3 ligand and also with the hydrophobic effect observed in other systems. The work has further confirmed that the combination of the cooperativity between two metal ions and a medium effect could result in excellent catalytic activities for the cleavage of phosphate diesters.

A rationally designed amphiphile containing a hydrophobic Hantzsch ester and a hydrophilic phosphate ester was able to form vesicles in aqueous solution, and resulted in the first example of a NO-responsive drug delivery system.

A series of bifunctional molecules with different combinations of macrocyclic polyamine [12]aneN3 and coumarin moieties, 4a/b and 5a/b, were synthesized by a two-step copper(I)-mediated alkyne–azide click reactions between 1,3,5-tris(azidomethyl)benzene and Boc-protected N-propynyl-[12]aneN3/7-propynyloxycoumarins. Agarose gel electrophoresis experiments indicated that bifunctional molecules 4b and 5b effectively induced complete plasmid DNA condensation at concentrations up to 40 μM. It was found that the structural variation had a major impact on the condensation behavior of these compounds. The electrostatic interaction involving the [12]aneN3 moiety can be compensated by the binding contribution of the coumarin units during the DNA condensation process. These two types of interaction showed different effects on the reversibility of DNA condensation. Results from studies using dynamic laser scattering, atomic force microscopy, and EB replacement assay further supported the above conclusion. Cytotoxicity assays on bifunctional compounds 4a/b and 5a/b indicated their low cytotoxicity. Results from cellular uptake and cell transfection experiments proved that bifunctional compounds 4b and 5b successfully served as non-viral gene vectors. Furthermore, methyl substituents attached to the coumarin unit (4b and 5b) greatly enhanced their DNA condensation capability and gene transfection. These bifunctional molecules, with the advantages of lower cytotoxicity, good water solubility, and potential structural modification, will have great potential for the development of new non-viral gene delivery agents.

A series of mono- and di-[12]aneN3 ligands 1–6, which contain different substituents on the coordinating backbone, different linkers between two [12]aneN3 units and different N-methylation on the [12]aneN3 units, have been synthesized and fully characterized. The catalytic activities of their metal complexes on the cleavage of RNA model phosphate 2-hydroxypropyl-p-nitrophenyl phosphate (HPNPP) varied with the structures of the ligands and metal ions. Click reactions afforded an efficient method to prepare a series of [12]aneN3 ligands, however, the incorporation of triazole moieties reduced the catalytic activities due to their coordination with metal ions and the strong inhibition from the triflate counter ion. Dinuclear zinc(II) complexes containing an m-xylyl bridge showed higher catalytic activities with synergistic effects up to 700-fold. Copper(II) complexes with the ligands without triazole moieties proved to be highly reactive and showed strong cooperativity between the two copper(II) ions. In terms of k2, dinuclear complexes Zn2-3b, Zn2-3d, Zn2-4b, and Cu2-4b afforded activities of 7.9 × 105, 3.9 × 104, 9.0 × 104, and 8.1 × 104-fold higher than that of methoxide. The ortho arrangement of the two [12]aneN3 units and the presence of 5- or 2-positioned substituents in the benzene ring as well as N-methylation of [12]aneN3 units greatly reduced the catalytic activities due to the steric effects. These results clearly indicate that the structures of the linker between two [12]aneN3 units play very important role in their catalytic synergistic effects.

Aromatic oligoureas 3 and 4 have urea moieties engaging in weak intramolecular H-bonding that constrains their backbones. The shorter 3a and 3b are able to bind chloride and acetate but not their corresponding counterion. The longer 4 binds both an anion and its counterion with the same affinity.

Small organic non-viral gene vectors with the structural combinations of (aliphatic chain)–naphthalimide–[12]aneN3 (11a, b) and naphthalimide–(aliphatic chain)–[12]aneN3 (12a–c) were synthesized and fully characterized. Agarose gel electrophoresis experiments indicated that the first type of compounds, 11a and 11b, could completely retard DNA at the concentration of 5 μM in the presence of DOPE. Within the second type of compounds, 12c with the decane chain showed a complete retardation of DNA at the concentration of 20 μM, whereas 12a and 12b with the ethyl and hexyl chains could not retard DNA effectively. Dynamic light scattering measurements indicated that compounds 11a, 11b and 12b, 12c condensed DNA into nanoparticles with the size in the range of 60–160 nm. Due to the strong fluorescence of 11a and 11b, the distribution of lipids/DNA complexes and the process of DNA release from the lipids were clearly observed via cellular uptake experiments. On the other hand, the non-fluorescent 12a–c enabled the EB exclusion assay to afford the binding constants of 4.88 × 106 M−1 (12a), 4.18 × 106 M−1 (12b) and 3.39 × 106 M−1 (12c), respectively. The MTT assay revealed that both types of compounds have low cytotoxicity. Non-fluorescent 12c was successfully applied in the eGFP expression experiments in A549 cells and showed stronger green fluorescence emission than that of lipofectamine 2000. Quantitative transfection experiments through the luciferase assay further revealed that compounds 11a, 11b and 12c can act as non-viral gene vectors in different cell lines. Among them, 12c gave the highest transfection efficiency in HeLa cells, which was about 2 times that offered by lipofectamine 2000. This work clearly demonstrated that the right combination of different functional units and long aliphatic linkers will likely promote gene delivery and transfection efficiency.

Three novel D–A–D type chromophores, consisting of substituted triphenylamine and aggregation-induced emission (AIE)-active tetraphenylethylene moieties, 1 (with two ethoxy groups), 2 (with two hydroxyl groups), 3 (non-substituted), were synthesized and characterized. Their one-photon excited fluorescence (OPEF) quantum yields (ΦF) and lifetimes (τ) in organic solutions increased with the increase of the electron-donating ability of the substituents on the triphenylamine unit, i.e., 1 > 2 > 3. By means of dynamic light scattering and scanning electron microscopy, it was found that the higher hydrophobicity of 1 resulted in larger particle sizes and a strong AIE effect. 1 and 2 showed good two-photon excited fluorescence (TPEF) and two-photon absorption cross-sections (σ) (4230 and 4004, respectively) and proved to have good biocompatibility. Both compounds 1 and 2 were successfully applied in cell imaging based on their OPEF and TPEF properties. This work clearly implies that these chromophores can be finely tuned for different optical properties and applications through varying the electron-donating ability, hydrophobicity, and cytotoxicity of the substituents.