Water-Soluble Metalloporphyrins as Mimics of Heme-containing Enzymes

Hemin is a naturally occurring metalloporphyrin (M-P), which is the common prosthetic group of heme-containing enzymes. Many M-Ps with different ligand structures and central metal ions were synthesized to mimic heme-containing enzymes1-3. To improve the catalytic capability and specificity of mimic enzyme, the effect of axial ligand was studied as well4-8. Similar to the active center of all heme-containing enzymes, M-P should show more or less catalytic activities of heme-containing enz…     

Enantioselective Artificial Receptors Formed by the Spreader‐Bar Technique

Chiroselective binding sites have been created on thin gold films by application of the spreader‐bar approach. Impedometric techniques and surface plasmon resonance were applied to detect binding. (R)‐(+)‐1,1′‐Binaphthyl‐2,2′‐diol (R‐BNOH) and (S)‐(?)‐1,1′‐binaphthyl‐2,2′‐diol (S‐BNOH) were used as model analytes. The artificial receptors were prepared by co‐adsorption of 16‐mercaptohexadecane (matrix) with a thiol‐modified chiral selector (template). The conjugates of D ,L ‐thioctic acid and (R)‐(+)‐ or (S)‐(?)‐1,1′‐binaphthyl‐2,2′‐diamine were used as templates. Different concentration ratios of the matrix and template were tested. No chiral selectivity of surfaces formed by either the matrix or the template alone was observed. The use of alkylthiols shorter than 16‐mercaptohexadecane led to the formation of surfaces with no chiral selectivity. The gold electrodes coated by the spreader‐bar technique displayed an enantioselectivity of up to 4.76 or up to 2.55 as measured by the capacitive and SPR methods, respectively.     

新型金属卟啉的合成及其仿酶活性研究

合成并表征了一系列水溶性和非水溶性金属卟啉3a～3e,5a～5f和8a～8f;测试了这些金属卟啉作为超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的模拟物催化歧化O₂-和催化分解H₂O₂等有毒氧自由基的活性及抗脂质过氧化性质.结果表明,含有吡啶溴化盐的水溶性金属卟啉8a～8f的仿酶活性明显大于含有羟基的非水溶性金属卟啉3a～3e和含有酯基的金属卟啉5a～5f.     

Phenanthrene‐Derived DNA Hairpin Mimics

Self‐complementary oligodeoxynucleotides containing 3,6‐disubstituted phenanthrenes adopt highly stable, hairpin‐like structures. The thermodynamic stability of the hairpin mimics depends on the overall length of the phenanthrene building block. Hairpin loops composed of a phenanthrene‐3,6‐dicarboxamide and ethylene linkers were found to be optimal. The hairpin mimics are more stable than the analogous hairpins containing either a dT₄ or dA₄ tetraloop. Model studies indicate that the thermodynamic stability of the hairpin mimics is primarily due to aromatic stacking of the phenanthrene‐3,6‐dicarboxamide onto the adjoining base pair of the DNA duplex.     

Modification of Cyclodextrins for Use as Artificial Enzymes

The magical powers of enzymes have been attributed to their ability to bind specific substrates and catalyze reactions of the bound substrate. Artificial enzymes synthetically mimic the binding and the catalytic site to produce molecules that are not only smaller in size but also potentially have similar activity to the real enzymes. The main objective of our research is to create artificial redox enzymes by using cyclodextrins as binding sites and attaching flavin derivatives as the catalytic site. We have developed a strategy to attach a catalytic site to cyclodextrin exclusively at the 2-, 3- or the 6-position. The evaluation of the artificial enzyme in which flavin is attached to the 2-position gives a 647-fold acceleration factor. Although this is modest compared to those of real enzymes (which can have acceleration factors of a trillion), the artificial enzymes allow us to understand the elements that contribute to the incredible catalytic power of enzymes.     

Functionalizable Stereocontrolled Cyclopolyethers by Ring‐Closing Metathesis as Natural Polymer Mimics

Whereas complex stereoregular cyclic architectures are commonplace in biomacromolecules, they remain rare in synthetic polymer chemistry, thus limiting the potential to develop synthetic mimics or advanced materials for biomedical applications. Herein we disclose the formation of a stereocontrolled 1,4‐linked six‐membered cyclopolyether prepared by ring‐closing metathesis (RCM). Ru‐mediated RCM, with careful control of the catalyst, concentration, and temperature, selectively affords the six‐membered‐ring cyclopolymer. Under optimized reaction conditions, no metathetical degradation, macrocycle formation, or cross‐linking was observed. Post‐polymerization modification by dihydroxylation afforded a novel polymer family encompassing a poly(ethylene glycol) backbone and sugar‐like functionalities (“PEGose”). This strategy also paves the way for using RCM as an efficient method to synthesize other stereocontrolled cyclopolymers.     

N‐Alkyl Ammonium Resorcinarene Salts as High‐Affinity Tetravalent Chloride Receptors

N‐Alkyl ammonium resorcinarene salts (NARYs, Y=triflate, picrate, nitrate, trifluoroacetates and NARBr) as tetravalent receptors, are shown to have a strong affinity for chlorides. The high affinity for chlorides was confirmed from a multitude of exchange experiments in solution (NMR and UV/Vis), gas phase (mass spectrometry), and solid‐state (X‐ray crystallography). A new tetra‐iodide resorcinarene salt (NARI) was isolated and fully characterized from exchange experiments in the solid‐state. Competition experiments with a known monovalent bis‐urea receptor ( 5 ) with strong affinity for chloride, reveals these receptors to have a much higher affinity for the first two chlorides, a similar affinity as 5 for the third chloride, and lower affinity for the fourth chloride. The receptors affinity toward chloride follows the trend K₁?K₂?K₃≈ 5 >K₄, with K_a=5011 m ^?1 for 5 in 9:1 CDCl₃/[D₆]DMSO.     

Xanthone O‐Glycosides from the Roots of Pteris Multifida

Two new xanthone glycosides and six known compounds were isolated from the roots of Pteris multifida. Based on spectroscopic and chemical methods, the structures of the new compounds were elucidated as 1‐hydroxy‐4,7‐dimethoxy‐8‐(3‐methyl‐2‐butenyl)‐6‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐[β‐D‐glucopyranosyl‐(1→3)]‐β‐D‐glucopyranosylxanthone ( 1 ), and 1,3‐dihydroxy‐7‐methoxy‐8‐(3‐methyl‐2‐butenyl)‐6‐O‐α‐L‐rhamnopyranosyl‐(1 →2)‐[β‐D‐glucopyranosyl‐(1→3)]‐β‐D‐glucopyranosylxanthone ( 2 ), respectively.     

水相中糖识别人工受体

自然界中,糖类不仅作为生命体系的能量物质和结构物质,而且还作为信息分子在生命过程的细胞识别和调控中扮演着重要的角色,因此对糖识别的研究将极大地有助于糖类参与生理和病理过程的研究。生命体系中糖识别过程一方面基于受体的极性基团与糖羟基的氢键作用,另一方面依靠受体结构中的含芳环非极性基团与糖CH基相互作用,所以在极性溶液水中通过非共价键相互作用实现糖识别过程是当今化学界一个十分吸引人且又极具挑战性的研究课题。人工合成糖识别受体为研究自然界中糖识别过程的基本机制提供了一种有参考价值的模型系统,同时为仿生应用提供了有力的技术支持。本文从超分子化学、多分枝型、合成凝集素类和聚合物界面4种体系论述了近年来非硼酸类人工糖识别受体在水相中识别糖的研究进展及其潜在应用,并且对合成凝集素和界面糖识别体系做了特殊点评,最后对仿生人工合成受体在水相中对糖识别的未来的发展方向做了展望。     

Unconventional Secondary Structure Mimics: Ladder‐Rungs

Secondary structures tend to be recognizable because they have repeating structural motifs, but mimicry of these does not have to follow such well‐defined patterns. Bioinformatics studies to match side‐chain orientations of a novel hydantoin triazole chemotype ( 1 ) to protein‐protein interfaces revealed it tends to align well across parallel and antiparallel sheets, like rungs on a ladder. One set of these overlays was observed for the protein‐protein interaction uPA?uPAR. Consequently, chemotype 1 was made with appropriate side‐chains to mimic uPA at this interface. Biophysical assays indicate these compounds did in fact bind uPAR, and elicit cellular responses that affected invasion, migration, and wound healing.     

Synthesis of Rhenium‐Centric Reverse Turn Mimics

Molecular scaffolds have been shown to facilitate and stabilise secondary structural turn elements, with a central core‐arranging functionality in a defined three‐dimensional orientation. In a peptide‐based molecular imaging probe, this approach is of particular value as it would essentially “hide” a metal radioisotope within the ligand framework, making the labelling element a critical component of the receptor‐bound structure. Starting from a 1,2‐diaminoethane loaded 2‐chlorotrityl resin, a versatile set of triamine ligand systems were synthesised by using solid‐phase Fmoc‐based peptide chemistry. The resultant resin‐bound peptides then underwent amide reduction by treatment with borane‐THF at 65 °C. This provided complete conversion to the corresponding polyamine entities in high purity for the majority of the amino acids utilised. The triamines were then coordinated on solid support by using [NEt₄]₂[Re(CO)₃(Br)₃] followed by resin cleavage and HPLC purification, to give the desired rhenium coordinated species. We have shown that amino acid sequences can be assembled, reduced and coordinated on‐resin, resulting in a versatile set of metal–ligand constructs. These studies could be expanded to generate libraries of turn‐based peptidomimetics containing Re/Tc^I organometallic scaffolds, with the intention of developing an improved approach for finding new diagnostic and therapeutic radiopharmaceutical entities.     

DNA-Based Artificial Receptors as Transmembrane Signal Transduction Systems for Protocellular Communication

The ability to reproduce signal transduction and cellular communication in artificial cell systems is significant in synthetic protobiology. Here, we describe an artificial transmembrane signal transduction through low pH-mediated formation of the i-motif and dimerization of DNA-based artificial membrane receptors, which is coupled to the occurrence of fluorescence resonance energy transfer and the activation of G-quadruplex/hemin-mediated fluorescence amplification inside giant unilamellar vesicles. Moreover, an intercellular signal communication model is established when the extravesicular H⁺ input is replaced by coacervate microdroplets, which activate the dimerization of the artificial receptors, and subsequent fluorescence production or polymerization in giant unilamellar vesicles. This study represents a crucial step towards designing artificial signalling systems with environmental response, and provides an opportunity to establish signalling networks in protocell colonies.     

New Oligosaccharide Esters and Xanthone C‐Glucosides from Polygala telephioides

Three new oligosaccharide esters named telephioses D ( 4 ), E ( 5 ), and F ( 6 ), and two new xanthone C‐glucosides, telephioxanthones A ( 7 ) and B ( 8 ), together with five known oligosaccharide esters and mangiferin, were isolated from the whole plant of Polygala telephioides Willd . The structures of the new compounds were elucidated on the basis of spectral data.