Probing the Hydrodynamic Behavior of Drug-Induced Tubulin Rings by Fluorescence Correlation Spectroscopy

We describe fluorescence correlation spectroscopy measurements of tubulin polymers composed of tubulin and either of two cytotoxic peptides – dolastatin 10 and cryptophycin 1. These peptides inhibit tubulin polymerization into microtubules, a major component of cellular networks, and instead induce the formation of predominantly single-walled tubulin rings. We determine ratios of the hydrodynamic diameter of dolastatin-tubulin or cryptophycin-tubulin polymers to that of tubulin dimers, which are compared with corresponding ratios calculated for two simple models: 1) a circular ring made with N contiguous spherical beads and 2) a circular ring constructed with N non-spherical monomers, each monomer being represented by 21-minibeads. We find that the computed ratios from the 21-minibead representation agree well with the measured ones when N = 28 and N = 16 for dolastatin-tubulin and cryptophycin-tubulin ring polymers, respectively. That is, the rings are made with 14 and 8 tubulin dimers, confirming the numbers derived by other techniques. The present results further support the applicability of theories that have been developed for calculating hydrodynamic properties of supramolecular biological structures.     

One-dimensional Coordination Polymers Assembled into Two Supramolecular Frameworks with High Stability

The dual ligand system of V-shaped 5-(4-carboxy-2-nitrophenoxy)-isophthalic acid(Hcn-H2ipa) and dipyridy-type molecules produces two new coordination polymers: {[Ni(cn-Hipa)(bpa)(H2O)3]·1.5H2O}n 1 and {[Cu(Hcn-ipa)(ppe)2]}n 2(bpa = 1,2-bis(4-pyridyl)ethane, and ppe = trans-1-(2-pyridyl)-2-(4-pyridyl)ethylene). Two complexes have been characterized by single-crystal X-ray diffraction, elemental analysis, IR, and thermogravimetric analysis(TGA). Complex 1 is of monoclinic system, space group C2 with a = 25.936(3), b = 7.6100(10), c = 16.558(2), β = 105.9470(10)°, V = 3142.4(7) ?3, Dc = 1.415 g/cm3, Mr = 669.23, Z = 4, F(000) = 1388, μ = 0.687 mm-1, the final R = 0.0397 and w R = 0.0967 for 12070 observed reflections with I 2σ(I). Complex 2 belongs to the triclinic system, space group P1 with a = 10.165(5), b = 14.946(7), c = 15.506(11) ?, α = 106.461(7), β = 102.454(8), γ = 107.861(5)°, V = 2029(2) ?3, Dc = 1.266 g/cm3, Mr = 773.20, Z = 2, F(000) = 794, μ = 0.595 mm-1, the final R = 0.0538 and w R = 0.1378 for 15488 observed reflections with I 2σ(I). Two complexes show that the 1D polymeric chains are cohered together by extensive H-bonds to complete stable supramolecular microporous frameworks.     

A Supramolecular Strategy for the Synthesis of Cyclic Oligomers and Polymers by Ring Expansion

Ring-opening metathesis polymerization (ROMP) of strained macrocycles is a key method to prepare diverse polymers. However, lack of ring strain in most macrocycles is an impediment to polymerization. In this paper, the polymerization/oligomerization of unstrained macrocycles was achieved using a supramolecular approach, leading selectively to cyclic products. Diphenyl thiourea and other guest molecules were used as additives to the ROMP reaction of unstrained macrocycles. An intermediate host-guest complex leads to the stabilization of the open form of the macrocycle after treatment with Grubbs catalysts, thereby favoring polymerization by inhibiting the ring-closing reaction back to the monomer. This proof-of-concept enables ring-expansion polymerization of unstrained macrocycles leading to cyclic polymers with molecular weights up to 6700 Da.     

Affinity Polymers Tailored for the Protein A Binding Site of Immunoglobulin G Proteins

Rational design in combination with a screening process was used to develop affinity polymers for a specific binding site on the surface of immunoglobulin G (IgG) proteins. The concept starts with the identification of critical amino acid residues on the protein interface and their topological arrangement. Appropriate binding monomers were subsequently synthesized. Together with a sugar monomer (2–5 equiv) for water solubility and a dansyl monomer (0.5 equiv) as a fluorescent label, they were subjected in aqueous solution to linear radical copolymerization in various compositions (e.g., azobisisobutyronitrile (AIBN), homogeneous water/DMF mixtures). After ultrafiltration and lyophilization, colorless dry water‐soluble powders were obtained. NMR spectroscopic and gel permeation chromatography (GPC) characterization indicated molecular weights between 30 and 500 kD and confirmed retention of monomer composition as well as the absence of monomers. In a competitive enzyme‐linked immunosorbent assay (ELISA) screen of the polymer libraries (20–50 members), few copolymers qualified as strong and selective binders for the protein A binding site on the Fc fragment of the antibody. Their monomer composition precisely reflected the critical amino acids found at the interface. The simple combination of a charged and a nonpolar binding monomer sufficed for selective submicromolar IgG recognition by the synthetic polymer. Affinities were confirmed by fluorescence titrations; they increased with decreasing salt load but remained largely unaltered at lowered pH. Other proteins, including those of similar size and isoelectric point (pI), were bound 10–1000 times less tightly. This example indicates that interaction domains in other proteins may also be targeted by synthetic polymers if their comonomer composition reflects the nature and arrangement of amino acid residues on the protein surface.     

Metal‐Containing Polymers: Building Blocks for Functional (Nano)Materials

The incorporation of metallic units into polymer chains has emerged as a promising route towards functional metal‐containing (nano)materials. The resulting polymers possess rich functions derived from their metallic elements, such as redox, optical, catalytic and magnetic properties. In addition, the directional and dynamic nature of metal coordination interactions provides further variables for the exploration of novel materials with designed nanostructures. These types of polymers can be synthesized through direct metal‐ligand coordination or chain polymerization of metal containing monomers. Depending on the polymerization techniques and starting components, the resulting polymers, akin to their organic counterparts, can be produced in the form of insoluble networks, processible chain structures, gels or colloids. Research into this rising multidisciplinary subject has benefited from recent progress in several related areas such as supramolecular chemistry, colloidal chemistry etc., with the combination of the relative merits of each ensuring further developments in each individual discipline. For example, as a result of studies into organometallic block copolymers self‐assembly behavior, living supramolecular polymerization has been unprecedentedly realized for the architectural design of micelles (see image on the right). Nevertheless, the field is still in a developmental stage and offers ample opportunities for fundamental research, as well as material exploration. In this Feature Article, we intend to overview the field with a brief survey of recent literature.

     

A Trefoil Knotted Polymer Produced through Ring Expansion

A synthetic strategy is reported for the production of a trefoil knotted polymer from a copper(I)‐templated helical knot precursor through ring expansion. The expected changes in the properties of the knotted polymer compared to a linear analogue, for example, reduced hydrodynamic radius and lower intrinsic viscosity, together with an atomic force microscopy (AFM) image of individual molecular knots, confirmed the formation of the resulting trefoil knotted polymer. The strategies employed here could be utilized to enrich the variety of available polymers with new architectures.     

Light-Induced Change of Charge Carrier Mobility in Semiconducting Polymers

Summary: Light-driven devices based on reversible change of carrier mobility in semiconducting polymers were investigated. The mobility was altered using a photochromic spiropyran capable of a reversible change of permanent dipole moment and ionization potential. While the latter attribute may result in formation of chemical traps and is more important for matrices with similar ionization potential such as PVK, the former phenomenon results in formation of polar traps and is more pronounced in the case of lower-band-gap materials.     

Supramolecular Fullerene Polymers and Networks Directed by Molecular Recognition between Calix[5]arene and C60

A biscalix[5]arene–C₆₀ supramolecular structure was utilized for the development of supramolecular fullerene polymers. Di‐ and tritopic hosts were developed to generate the linear and network supramolecular polymers through the complexation of a dumbbell‐shaped fullerene. The molecular association between the hosts and the fullerene were carefully studied by using ¹H NMR, UV/Vis absorption, and fluorescence spectroscopy. The formation of the supramolecular fullerene polymers and networks was confirmed by diffusion‐ordered ¹H NMR spectroscopy (DOSY) and solution viscometry. Upon concentrating the mixtures of di‐ or tritopic hosts and dumbbell‐shaped fullerene in the range of 1.0–10 mmol L^?1, the diffusion coefficients of the complexes decreased, and the solution viscosities increased, suggesting that large polymeric assemblies were formed in solution. Scanning electron microscopy (SEM) was used to image the supramolecular fullerene polymers and networks. Atomic force microscopy (AFM) provided insight into the morphology of the supramolecular polymers. A mixture of the homoditopic host and the fullerene resulted in fibers with a height of (1.4±0.1) nm and a width of (5.0±0.8) nm. Interdigitation of the alkyl side chains provided secondary interchain interactions that facilitated supramolecular organization. The homotritopic host generated the supramolecular networks with the dumbbell‐shaped fullerene. Honeycomb sheet‐like structures with many voids were found. The growth of the supramolecular polymers is evidently governed by the shape, dimension, and directionality of the monomers.     

Inversion of Supramolecular Helicity in Oligo‐p‐phenylene‐Based Supramolecular Polymers: Influence of Molecular Atropisomerism

The helical organization of oligo‐p‐phenylene‐based organogelators has been investigated by atomic force microscopy, circular and vibrational circular dichroism, and Raman techniques. Whilst OPPs with more than two phenyl rings in the core self‐assemble into left‐handed helices, that with a biphenyl core shows an inversion of the supramolecular helicity depending on the formation conditions through the atropisomerism of the biphenyl central unit. The results presented herein outline a new example of kinetically controlled modulation of supramolecular helicity.     

Synthesis and Characterization of Photoactive Amphiphilic Polymers

We have synthesized light sensitive nano micelles for their applications as drug delivery agents. Various azo compounds having different dipole moment values have been covalently attached to an amphiphilic pegylated co‐polymer and their light sensitive behavior has been studied in both aqueous and organic media with ultra violet light to understand the light dependent supramolecular organization.     

呋喃稠环类共轭有机分子和聚合物研究进展

目前,噻吩稠环衍生物及相关共轭聚合物作为有机半导体材料已经得到了较多的研究和应用.呋喃作为一种与噻吩杂原子同主族的五元环体系,与噻吩具有类似的化学结构和电子性质,但其具有芳香性更小、载流子迁移率高、荧光量子效率高和溶解性好的特点,得到了越来越多的研究和关注.本综述介绍了呋喃稠环共轭有机分子与呋喃稠环共轭聚合物的合成方法、性质及应用.     

Synthesis and Self Assembly of Hydrogen-Bonded Supramolecular Polymers

New synthetic methodologies towards hydrogen bonded supramolecular polymers are described. Focus is directed on synthetic work towards telechelics with hydrogen bonds either as side chain moieties or as endgroups. Physical ordering effects related to polymers and particles are discussed citing own and related work in ∼60 references.     

Ring Contraction by NHC‐Induced Pnictogen Abstraction

The reaction of [Cp′′′Co(η⁴‐P₄)] ( 1 ) (Cp′′′=1,2,4‐tBu₃C₅H₂) with ^MeNHC (^MeNHC=1,3,4,5‐tetramethylimidazol‐2‐ylidene) leads through NHC‐induced phosphorus cation abstraction to the ring contraction product [(^MeNHC)₂P][Cp′′′Co(η³‐P₃)] ( 2 ), which represents the first example of an anionic CoP₃ complex. Such NHC‐induced ring contraction reactions are also applicable for triple‐decker sandwich complexes. The complexes [(Cp*Mo)₂(μ,η^6:6‐E₆)] ( 3 a , 3 b ) (Cp*=C₅Me₅; E=P, As) can be transformed to the complexes [(^MeNHC)₂E][(Cp*M)₂(μ,η^3:3‐E₃)(μ,η^2:2‐E₂)] ( 4 a , 4 b ), with 4 b representing the first structurally characterized example of an NHC‐substituted As^I cation. Further, the reaction of the vanadium complex [(Cp*V)₂(μ,η^6:6‐P₆)] ( 5 ) with ^MeNHC results in the formation of the unprecedented complexes [(^MeNHC)₂P][(Cp*V)₂(μ,η^6:6‐P₆)] ( 6 ), [(^MeNHC)₂P][(Cp*V)₂(μ,η^5:5‐P₅)] ( 7 ) and [(Cp*V)₂(μ,η^3:3‐P₃)(μ,η^1:1‐P{^MeNHC})] ( 8 ).     

Radius of Gyration,Mean Span,and Geometric Shrinking Factors of Bridged Polycyclic Ring Polymers

This study concerns the equilibrium geometric properties of a family of cyclic chains, referred to as the “bridged polycyclic rings,” which have f flexible subchains bridging two common branch points. By increasing the number of bridges, f, this family encompasses the usual linear chain (f = 1), monocyclic ring (f = 2), bicyclic θ‐shaped polymer (f = 3), and multicyclic rings with increasing topological complexity. Results of their radius of gyration, mean span, and, consequently, geometric shrinking factors (also known as the g‐factors) are obtained by three approaches—the Gaussian chain theory, simulations based on the Kremer–Grest bead‐spring model, and a Flory‐type mean‐field approach. Using the confinement analysis from bulk structures method, the equilibrium partition coefficients (K) of several of those cyclic excluded volume chains in a cylindrical pore with inert surfaces are obtained, and the results fall onto a common curve on a graph of K versus the polymer‐to‐pore size ratio, using the mean span as the representative polymer size, in the range of K relevant to polymer separation in size exclusion chromatography (SEC) experiments. Applications of the results in predicting the SEC retention volume of such bridged polycyclic ring polymers are discussed in the framework of the equilibrium partition theory.

     

Study of supramolecular side‐chain and cross‐linking polymers by complexation of various H‐donor acids with H‐acceptor copolymers containing pendent carbazole and fluorescent pyridyl units

Two H‐bonded acceptor (H‐acceptor) homopolymers 14 and 17 were successfully prepared by polymerization of fluorescent pyridyl monomers PBT and PBOT ( 12 and 13 ), which were synthesized via Sonogashira coupling and Wittig‐Horner reactions. To increase the glass transition temperatures as well as reduce the π‐π stacking of the photoluminescent (PL) H‐acceptor copolymers and their H‐bonded polymer complexes, fluorescent monomers 12 and 13 were copolymerized with N‐vinylcarbazole monomer CAZ (23) to produce H‐acceptor copolymers 15–16 and 18–19 . Supramolecular side‐chain and crosslinking polymers (i.e., H‐bonded polymer complexes) obtained by complexation of light‐emitting H‐acceptor polymers 14–19 with various proton donor (H‐donor) acids 20–22 were further characterized by DSC, POM, FTIR, XRD, and PL measurements. The mesomorphic properties can be tuned from the nematic phase in H‐acceptor homopolymers ( 14 and 17 ) to the tilted smectic C phase in their H‐bonded polymer complexes ( 14/20–21 and 17/20–22 ) by the introduction of H‐donor acids (20–22). Moreover, the PL properties of light‐emitting H‐acceptor polymers can be adjusted not only by the central structures of the conjugated pyridyl cores but also by their surrounding nonfluorescent H‐donor acids. In general, redder shifts of PL emissions in H‐bonded polymer complexes occurred when the light‐emitting H‐acceptor polymers were complexed with H‐donors having smaller pKa values. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2734–2753, 2009     

沙拉沙星分子印迹聚合物的制备及其吸附特性

以沙拉沙星为模板分子、甲基丙烯酸为功能单体和乙二醇二甲基丙烯酸酯为交联剂合成了分子印迹聚合物 ,并用平衡吸附实验研究了其吸附性能。结果表明 :该聚合物对沙拉沙星有较高的亲和性和选择性 ,解离常数Kd=7.2 6× 10 - 7～ 2 .19× 10 - 5mol L。