Guo-Yuan Lu

DNA binding, cleavage, and cytotoxic activity of the preorganized dinuclear zinc(II) complex of triazacyclononane derivatives.

A preorganized cleft dinuclear zinc(II) complex of 2,6-bis(1-methyl-1,4,7-triazacyclonon-1-yl)pyridine 1 as an artificial nuclease was prepared via an improved method. The interactions of 1, 2 [1,4,7-triazacyclononane (TACN)], and their zinc(II) complexes with calf thymus DNA were studied by spectroscopic techniques, including fluorescence and CD spectroscopy. The results indicate that the DNA binding affinities of these compounds are in the following order: Zn(II)2 -1 > Zn(II) -2 > 1 > 2. The binding constants of the Zn (II)2 -1 and Zn(II)-2 complexes are 3.57 x 10(6) and 1.43 x 10(5) M(-1), respectively. Agarose gel electrophoresis was used to assess the plasmid pUC 19 DNA cleavage activities in the presence of the dinuclear Zn (II)2 -1 complex, which exhibits powerful DNA cleavage efficiency. Kinetic data for DNA cleavage promoted by the Zn(II)2 -1 complex under physiological conditions give the observed rate constant ( k obs) of 0.136 h(-1), which shows an 10(7)-fold rate acceleration over uncatalyzed supercoiled DNA. The comparison of the dinuclear Zn(II)2 -1 complex with the mononuclear zinc(II) complex of 1,4,7-triazacyclononane indicates that the DNA cleavage acceleration promoted by the Zn(II)2 -1 complex is due to the efficient cooperative catalysis of the two proximate zinc(II) cation centers. A hydrolytic mechanism of the cleavage process was suggested, and a preliminary study of the antitumor activity was also conducted.

DNA binding and cleaving activity of the new cleft molecule N,N'-Bis(guanidinoethyl)-2,6-pyridinedicarboxamide in the absence or in the presence of copper(II).

Novel cleft molecule pyridine-2,6-dicarboxamide appending two guanidinoethyl group side arms (Gua) was synthesized. The interactions of the cleft molecule in the absence of copper(II) (Gua) or in the presence of copper(II) (Cu2+-Gua) with calf thymus DNA were studied by fluorescence and CD spectroscopy. The results indicate that the DNA binding affinity of Cu2+-Gua is stronger than that of Gua, and the binding constants of Cu2+-Gua and Gua are 1.61 x 10(6) M(-1) and 2.86 x 10(5) M(-1), respectively. Agarose gel electrophoresis was used to assess the plasmid pUC 19 DNA cleavage activities in the presence of Gua and Cu2+-Gua. Kinetic data of DNA cleavage promoted by Cu2+-Gua under physiological conditions fit a saturation kinetic profile with k(max) of 0.0173 +/- 0.0011 h(-1), which gave a aproximately 10(6)-fold rate acceleration over uncatalyzed supercoiled DNA, while the catalyst concentration is lower than 0.0625 mM. The hydrolysis pathway was proposed as the possible mechanism for DNA cleavage promoted by Cu2+-Gua. The acceleration is due to efficient cooperative catalysis of the copper cation center and the functional groups (bis(guanidinium) groups).

A fluorometric/colorimetric dual-channel Hg2+ sensor derived from a 4-amino-7-nitro-benzoxadiazole (ANBD) fluorophore

A new visible light excitable Hg2+ sensor, NBD-TAEE, was prepared by bridging a 4-amino-7-nitro-benzoxadiazole (ANBD) fluorophore with thiaazacrown ethervia an ethylene spacer. Besides the specific Hg2+-induced absorption shift from 466 to 513 nm, this sensor exhibits the specific Hg2+-induced emission enhancement (∼29-fold) and fluorescent pH-independence from pH 6 to 13. Hg2+ addition even leads to the emission red shift from 532 to 570 nm, although NBD-TAEE is not a ratiometric fluorescent sensor due to its emission band being overlaid by the Hg2+-induced band. The instant and reversible “turn-on” Hg2+ response, fine cell permeability and cell imaging ability display its potential application in both environmental and Hg2+-polluted biological samples. Its analogue without the ethylene spacer, NBD-TAE, possesses the higher quantum yield and very poor Hg2+ binding ability. Their different emission behavior and sensing ability suggest that the spacer is quite essential for sensor construction.

Molecular recognition of nucleotides by a calix[4]arene derivative with two alkyl guanidinium groups at the air–water interface

Monolayers of 5,11,17,23-tetra-tert-butyl-25,27-bis(2-guanidinoethoxy)-26,28-dihydroxy calix[4]arene hydrochloride (BGC) on the surface of pure water and of aqueous subphases containing 5′-AMP− and 5′-GMP2− were studied by film balance measurements and relaxation experiments. LB films deposited from the monolayers on the three kinds of subphases were investigated by ultraviolet visible spectra (UV), circular dichroism spectra (CD), Fourier transform infrared spectra (FT-IR) and X-ray photoelectron spectra (XPS). All the results indicate that BGC can form stable monolayers on these different subphases. Moreover, BGC can effectively bind with 5′-AMP− and 5′-GMP2− dissolved in the subphase by complementary hydrogen bonding and electrostatic interactions in 1∶1 and 2∶1 molar ratios, respectively. Two intermolecular interaction patterns are proposed and the binding constants are estimated to be 1 ± 0.5 × 106 and 6 ± 1 × 105 M−1, respectively.

Supramolecular interaction of diamino calix[4]arene derivative with nucleotides at the air–water interface

Abstract The properties of the monolayer of 5,11,17,23-tetra- tert -butyl-25,27-bis (2-aminoexthoxy)-26,28-dihydroxycalix[4]arene and its recognition capacity for 5′-AMP − and 5′-GMP 2− at the air–water interface were investigated. π– A isotherms and relaxation experiments indicate that it is able to form stable monolayers on pure water and two nucleotide-containing subphases. Moreover, the nucleotides in subphase are beneficial to the stability of its monolayer. The UV, CD, and FT-IR spectra of LB films from three subphases reveal that 5′-AMP − and 5′-GMP 2− in subphase can be transferred onto the substrates along with the monolayer mainly via multiple hydrogen bonding and electrostatic interactions. The host–guest complexes of 5,11,17,23-tetra- tert -butyl-25,27-bis(2-aminoexthoxy)-26,28-dihydroxycalix[4]arene and nucleotides at the air–water interface were studied through the analysis of the X-ray photoelectron spectra data of LB films. The results indicate that 5′-AMP − and 5′-GMP 2− were bound to the calix[4]arene monolayer in 1:1 and 1:2 molar ratio, respectively. Two intermolecular interaction patterns are proposed and the binding constants are estimated to be 1.4±0.1×10 5 and 1.1±0.2×10 5 M −1 for 5′-AMP − and 5′-GMP 2− , respectively.

Significant effect of bromo substituents on nonlinear optical properties of polymer and chromophores.

Four chromophores containing bromo substituents, a ployimide with bromo-containing chromophores, four reference functional polyimides, and fourteen reference chromophores were synthesized for studying effect of bromo substituents on nonlinear optical (NLO) properties of materials and chromophores. The results of hyper-Rayleigh scattering and UV-vis spectra show that static first molecular hyperpolarizability (beta(0)) values of bromo-containing chromophores are 1.24-5.75 times as beta(0) of the corresponding chloro-containing chromophores (Hammett constants sigma of chloro and bromo groups are same) without causing a visible shift of the absorption band to longer wavelength. UV-vis spectra and the results of Maker Fringe method show that the polyimide with chromophores containing bromo substituents exhibits a good optical transparency and a much higher macroscopic nonlinear optical coefficient (d(33) = 20.1 pm/V) than the reference polyimides containing nitro (d(33) = 9.6 pm/V) and cyano (d(33) = 8.9 pm/V) groups in spite of nitro and cyano groups being strong electron acceptors. d(33) of polyimide with chloro-containing chromophores is very small. Therefore, this paper suggests an effective strategy for improving the NLO properties of polymeric materials and chromophores without reducing optical transparency in designing NLO polymers and chromophores. On the basis of quantum chemistry calculations, the reasons of effect of bromo substituents on NLO properties of chromophores and materials were discussed.

Total synthesis of non-natural compounds for molecular recognition. The double challenge

Molecular recognition of biomolecules by synthetic receptors requires modular assembly of various components to complement the molecular characteristics (sizes, topologies, and functional groups) of the substrate. A number of receptors for biorelevant molecules containing oxoanions have been assembled from a bicyclic chiral guanidine subunit. Several receptors accelerate or catalyze reactions proceeding through anionic transition states. Among the structures recently prepared, a receptor incorporating a calix(6)arene subunit has been developed, showing high affhity for phosphocholine derivatives. Chains of tetraguanidinium sulfates form double helices in solution. These substances strongly induce formation of a-helical conformations in Asp rich peptides.

Synthesis and DNA cleavage activity of 2-hydrazinyl-1,4,5,6-tetrahydropyrimidine containing hydroxy group.

2-Hydrazinyl-1,4,5,6-tetrahydropyrimidin-5-ol dihydrochloride 2, as well as 2-hydrazinyl-4,5-dihydro-1H-imidazole dihydrochloride 1, was synthesized as metal-free DNA cleaving agent. Agarose gel electrophoresis was used to assess the plasmid pUC 19 DNA cleavage activities in the presence of 1 and 2. DNA cleavage efficiency of 2 exhibits remarkable increases compared with its corresponding non-hydroxy compound 1. Kinetic data of DNA cleavage promoted by 2 fit to the Michaelis-Menten-type equation with k(max) of 0.0378+/-0.0013 h(-1) giving 10(6)-fold rate acceleration over uncatalyzed DNA. The acceleration is driven by the spatial proximity of the nucleophilic hydroxy group and the electrophilic activation for the phosphodiester by the ammonium and/or guanidinium groups. In vitro cytotoxic activities toward Hela cells and human leukemia HL-60 cells were also examined, and 2 exhibits stronger cytotoxic activities than 1.

p-Nitrophenylazo Calix[4]arenes, Synthesis, Monolayers and NLO-properties

The mono, bis, tris and tetrakis (p-nitrophenyl)azo calix[4]arenes (1, 2, 3 and 4) with NLO properties are synthesized by the diazo-coupling of calix[4]arene with p-nitrophenyl diazonium. HRS measurements at 1064 nm indicate that (p-nitrophenyl)azo calix[4]arenes have higher second-order hyperpolarizability β values than the corresponding reference compound 4-(4-nitrophenylazo)-2,6-dimethylphenol, without red shift of the charge transfer band. The bis and tris (p-nitrophenyl)azo calix[4]arenes (2, 3) without hydrophobic alkyl chains can form stable Langmuri monolayers at the air/water interface because of arene π–π stacking.

Synthesis and DNA cleavage activity of triazacrown-anthraquinone conjugates

1,4,7-Triazacyclononane (TACN), with DNA cleaving ability, was appended to anthraquinone via different spacers to construct the new compounds 1,8-[2,2′-(1,4,7-triazacyclonon)diethoxy] anthracene-9,10-dione hydrochloride (1) and 1,8-[2,2′-(1,4,7-triazacyclonon)dihexyloxy] anthracene-9,10-dione hydrochloride (2) as new agents for metal-free DNA cleavage. Fluorescence and CD spectroscopic studies suggest an intercalating DNA binding mode, and the apparent DNA binding constants of 1 and 2 are 3.93 × 107 and 6.07 × 107 M−1, respectively. Compound 2, bearing the longer spacer, exhibits the higher DNA binding ability. The apparent initial first-order rate constant (kobs) of DNA cleavage promoted by 1 and 2 (0.05 mM) in physiological media are 0.077 ± 0.0028 and 0.123 ± 0.0027 h−1, respectively. The 51-fold and 82-fold rate accelerations over parent TACN (the kobs is 0.0015 ± 0.00003 h−1 (0.05 mM) under the same conditions) are due to the anthraquinone moiety of compounds 1 and 2 intercalating into the DNA base pairs via stacking interactions. ESI-MS analysis of the dinucleotide cleavage promoted by 1 and 2, and radical scavenger inhibition studies suggest that the cleavage process is a hydrolytic mechanism.