Hierarchical Analysis of Self‐Assembled PEGylated Hexaphenylalanine Photoluminescent Nanostructures

Despite the growing literature about diphenylalanine‐based peptide materials, it still remains a challenge to delineate the theoretical insight into peptide nanostructure formation and the structural features that could permit materials with enhanced properties to be engineered. Herein, we report the synthesis of a novel peptide building block composed of six phenylalanine residues and eight PEG units, PEG₈‐F6. This aromatic peptide self‐assembles in water in stable and well‐ordered nanostructures with optoelectronic properties. A variety of techniques, such as fluorescence, FTIR, CD, DLS, SEM, SAXS, and WAXS allowed us to correlate the photoluminescence properties of the self‐assembled nanostructures with the structural organization of the peptide building block at the micro‐ and nanoscale. Finally, a model of hexaphenylalanine in aqueous solution by molecular dynamics simulations is presented to suggest structural and energetic factors controlling the formation of nanostructures.     

1－芘甲基十二烷基醚的簇集行为研究及其在簇集体结构－极性关系中的应用

基于芘的荧光发射单体峰的相对强度对环境极性的敏感这一性质，设计并合成了芘标记的长链荧光探针。采用稳态荧光发射光谱和激发光谱以及紫外吸收光谱研究了该探针的簇集行为。发现其极性在临界簇集浓度附近发生突变，可以用来表征簇集。随后用它作为极性探针，研究了三个长链烷烃，三个胆固醇酯和三个含支甲基的化合物的结构与它们形成的簇集体的极性的关系,并用链长效应和支甲基效应对这些关系做了讨论。根据这些结果对簇集体的结构性质做了推测。     

The Introduction of a Cysteine Residue Modulates The Mechanical Properties of Aromatic-Based Solid Aggregates and Self-Supporting Hydrogels

Peptide-based hydrogels, originated by multiscale self-assembling phenomenon, have been proposed as multivalent tools in different technological areas. Structural studies and molecular dynamics simulations pointed out the capability of completely aromatic peptides to gelificate if hydrophilic and hydrophobic forces are opportunely balanced. Here, the effect produced by the introduction of a Cys residue in the heteroaromatic sequence of (FY)3 and in its PEGylated variant was evaluated. The physicochemical characterization indicates that both FYFCFYF and PEG8-FYFCFYF are able to self-assemble in supramolecular nanostructures whose basic cross-β motif resembles the one detected in the ancestor (FY)3 assemblies. However, gelification occurs only for FYFCFYF at a concentration of 1.5 wt%. After cross-linking of cysteine residues, the hydrogel undergoes to an improvement of the rigidity compared to the parent (FY)3 assemblies as suggested by the storage modulus (G’) that increases from 970 to 3360 Pa. The mechanical properties of FYFCFYF are compatible with its potential application in bone tissue regeneration. Moreover, the avalaibility of a Cys residue in the middle of the peptide sequence could allow the hydrogel derivatization with targeting moieties or with biologically relevant molecules.     

Aggregation behaviour of a novel series of polyamidoamine-based dendrimers in aqueous solution

Dendrimers composed of G1 polyamidoamine branched with poly(propylene oxide) (PPO)-block-poly(ethylene oxide) (PEO) were synthesised for the first time. Surface tension results showed an increase in the critical aggregation concentration (cac) with PPO-b-PEO chain lengthening. The thermodynamic parameters associated with aggregate formation were determined by isothermal titration microcalorimetry, indicating that both the cac and the Gibbs free energy for aggregation (ΔG°) ascended as the amphiphilic chain length increased. The gain of entropy (ΔS°) was the main contribution to aggregation due to TΔS° being larger than the enthalpy (ΔH°). Aggregate morphology and size distribution were studied through transmission electron microscope and dynamic light scattering measurements. Furthermore, the relationship between PEO chain length and aggregation behaviour was discussed.     

The critical aggregation concentration of peptide surfactants is predictable from dynamic hydrophobic property

Peptide surfactants are a kind of newly emerged functional materials, which have a variety of applications such as building nanoarchitecture, stabilizing membrane proteins and controlling drug release. In the present study, we report the modelling and prediction of critical aggregation concentration (CAC), an important parameter that characterizes the self-assembling behaviour of peptide surfactants through the use of statistical modelling and quantitative structure–property relationship (QSPR) approaches. In order to accurately describe the structural and physicochemical properties of the highly flexible peptide molecules, a new method called molecular dynamics-based hydrophobic cross-field (MD-HCF) is proposed to capture both the hydrophobic profile and dynamic feature of 32 surface-activity, structure-known peptides. A number of statistical models are then developed using partial least squares (PLS) regression with or without improvement by genetic algorithm (GA). We demonstrate that MD-HCF performs much better than the widely used CODESSA method in both its predictability and interpretability. We also highlight the importance of dynamic hydrophobic property in accurate prediction and reasonable explanation of peptide self-assembling behaviour in solution, albeit which is exhaustive to compute compared with those derived directly from peptide static structure. To the best of our knowledge, this study is the first to computationally model and predict the self-assembling behaviour of peptide surfactants.     

Characterization of PEGylated Asparaginase: New Opportunities from NMR Analysis of Large PEGylated Therapeutics

Resonance assignment and structural characterization of pharmacologically relevant proteins promise to improve understanding and safety of these proteins by rational design. However, the PEG coating that is used to evade the immune system also causes these molecules to “evade” the standard structural biology methodologies. We here demonstrate that it is possible to obtain the resonance assignment and a reliable structural model of large PEGylated proteins through an integrated approach encompassing NMR and X-ray crystallography.     

聚环氧乙烷修饰的芘用于“荧光开”检测胰蛋白酶的研究

本文采用聚环氧乙烷(PEO)对疏水染料芘进行亲水化修饰设计,以获得具有良好水溶性和荧光性能的两亲性探针分子聚环氧乙烷修饰的芘(PEO-Py).以牛血清白蛋白(BSA)作为胰蛋白酶的水解底物以及猝灭剂,BSA加入会通过动态猝灭使荧光强度降低.加入胰蛋白酶水解后,荧光强度部分恢复,建立了基于荧光强度升高的“荧光开”胰蛋白酶检测方法.对胰蛋白酶的检测限可达到9.8 μg·mL-1,检测线性范围为0～0.075 mg·mL-1.其他蛋白不会引起荧光强度的降低,检测体系具有良好的选择性.通过亲水化修饰提高了芘衍生物的水溶性,建立了制备简单、成本低、水溶性好的检测探针,拓展了芘在生理环境中的检测应用.     

支链烷基苯磺酸钠聚集性质的实验与理论研究

以芘为探针、二苯酮为猝灭剂,用稳态荧光法测定了合成的4种链长分别为10、12、14、16碳,苯环均在β位取代的对烷基苯磺酸钠的临界胶团浓度、胶团聚集数和微极性.研究了链长对支链烷基苯磺酸钠聚集性质的影响.分析了支链烷基苯磺酸钠疏水、亲水基团对聚集性质的影响.用量子化学从头算Hartree Fock方法取6 31G 基组计算了支链烷基苯磺酸根离子气相中的电荷分布.     

荧光性聚酰胺-胺树形分子在潜指纹显现中的应用研究

本文系统研究了不同条件(树形分子代数、浓度、浸泡时间等)下荧光性聚酰胺-胺树形分子(PAMAM)水溶液作为荧光探针对锡纸、透明胶带等基底上油印潜指纹的显现效果.结果发现PAMAM树形分子可以和指纹残留物进行靶向结合.结合到指纹纹线上的该荧光性纳米材料在暗室中365 nm紫外光的激发下发出明亮的蓝色荧光,指印纹线与基底反差大、指纹易于辨认,且操作简单,试剂完全环保无污染.这些结果表明PAMAM水溶液是一种潜在的优良的指纹显现试剂.最后,把PAMAM树形分子水溶液对指纹的显现效果进行量化处理,乳突纹与基底间的灰度对比度达到90%以上.     

Synthesis of poly(cystine bisamide)‐PEG block copolymers grafted with 1‐(3‐aminopropyl)imidazole and their phase transition behaviors

New biodegradable and pH‐sensitive block copolymers were prepared by grafting 1‐(3‐aminopropyl) imidazole onto a backbone polymer formed via condensation polymerization between l ‐cystine and EDTA‐dianhydride. The copolymer with a graft ratio of 79% exhibited a good buffering capacity and pH sensitivity. These are attributed to protonation–deprotonation of the imidazole ring at around pH 7. The copolymers with less imidazole content did not show any apparent responses to changes in pH. The particle size of the copolymer aggregate formed under basic conditions was around 200 nm and increased with decreasing pH. The critical aggregation values at pH 6.0 and 8.0, derived from the changes of intensity ratios (I₁/I₃) in the emission spectrums of pyrene, were approximately 0.17 and 0.05 mg/ml, respectively. The surface charge of the aggregates increased with the decreasing pH as a result of the increase in protonation of imidazole and the tertiary amine in the polymer chain. The microviscosity of hydrophobic domains was estimated using 1,6‐diphenyl‐1,3,5‐hexatriene. The decrease of the anisotropy value under acidic conditions reflects a disruption of hydrophobic interaction. Copyright © 2008 John Wiley & Sons, Ltd.     

疏水改性羟乙基纤维素的流变性能研究

对疏水改性羟乙基纤维素(HMHEC)溶液的流变性质进行了系统研究,探讨了不同的浓度、温度、盐浓 度、pH值和剪切速率对其溶液表观粘度的影响.结果表明HMHEC溶液临界缔合浓度为0.3 g/100 ml.当HMHEC的浓度低于临界缔合浓度时,HMHEC溶液增稠以分子内缔合为主,增稠幅度小;当高于临界缔合浓度后,便会形成以大分子间缔合为主的动态物理交联网络结构.HMHEC水溶液具有良好的耐温耐盐及抗剪切性能,而且pH稳定性良好.     

Effect of compressed CO2 on the critical micelle concentration and aggregation number of AOT reverse micelles in isooctane

The effect of compressed CO2 on the critical micelle concentration (cmc) and aggregation number of sodium bis-2-ethylhexylsulfosuccinate (AOT) reverse micelles in isooctane solution was studied by UV/Vis and fluorescence spectroscopy methods in the temperature range of 303.2-318.2 K and at different pressures or mole fractions of CO2 (X(CO2)). The capacity of the reverse micelles to solubilize water was also determined by direct observation. The standard Gibbs free energy (DeltaGo(m)), standard enthalpy (DeltaHo(m)), and standard entropy (DeltaSo(m)) for the formation of the reverse micelles were calculated by using the cmc data determined. It was discovered that the cmc versus X(CO2) curve and the DeltaGo(m) versus X(CO2) curve for a fixed temperature have a minimum, and the aggregation number and water-solubilization capacity of the reverse micelles reach a maximum at the X(CO2) value corresponding to that minimum. These results indicate that CO2 at a suitable concentration favors the formation of and can stabilize AOT reverse micelles. A detailed thermodynamic study showed that the driving force for the formation of the reverse micelles is entropy.     

Photoluminescence of Diphenylalanine Peptide Nano/Microstructures: From Mechanisms to Applications

Diphenylalanine (Phe‐Phe, FF) molecules, which can self‐assemble into highly ordered nano/microstructures, have increasingly aroused intense interests due to their special optical properties. In this review, recent advances in photoluminescence (PL) of supramolecular architectures of FF‐based peptide and the underlying mechanisms are highlighted. Mainly deep ultraviolet emission at around 285 nm and/or blue emission at ≈450 nm are observed in various FF peptide structures and its derivatives, which are primarily interpreted by quantum confinement effects, shallow radiative traps, and electron delocalization via hydrogen bonds in β‐ sheet structures. Furthermore, current applications of such fluorescent peptide nano/microstructures are also reviewed here, e.g., probing the number of water molecules confined in FF, temperature sensing, and visualization of deep ultraviolet beam. Yet, the PL mechanism is still under fierce debate and the application based on fluorescence is constantly under exploration. Thus, this review is endeavored to boost future explorations on the PL of the bioinspired FF peptide nano/microstructures.     

Dynamic Timing Control of Molecular Photoluminescent Systems

Dynamic control of molecular photoluminescence offers chemical solutions to designing functional emissive materials. Although stimuli-switchable molecular luminescent systems are well established, how to encode these dynamic emissive systems with a “timing” feature, that is, time-dependent luminescent properties, remains challenging. This Concept aims to summarize the design principles of dynamic timing molecular photoluminescent systems by discussing the state-of-the-art of this topic and the shaping of fabrication strategies at both the molecular and supramolecular levels. An outlook and perspectives are given to outline the future opportunities and challenges in the rational design and potential applications of these smart emissive systems.     

Thermodynamics of interaction between sodium bis(2‐ethylhexyl) sulfosuccinae and polymers in aqueous solutions by isothermal titration microcalorimetry

The interactions between sodium bis(2‐ethylhexyl) sulfosuccinae (AOT) and two nonionic water‐soluble polymers, including polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG) have been investigated by using isothermal titration microcalorimetry in aqueous solutions at 298.15 K. The results show that the critical aggregation concentration, which corresponding to the first turning point in the curve of experimental interaction heat versus concentration of the surfactant, is lower than the critical micellar concentration (cmc), confirming the existence of polymer‐surfactant interactions. The value of cac is not sensitive to the relative amount of polymer in low concentration range of the polymer. The mono‐layer saturated adsorption concentration, which corresponding to the second turning point, rises as the polymer concentration is increased. The interaction between PVP and AOT is stronger than that between PEG and AOT. The results also indicate that the aggregation of AOT in water and polymers solutions is entropically driven. The observed thermal effects have been interpreted in terms of the interactions of the polymer molecules with AOT monomers or the molecular clusters. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 275–283, 2006     

Realignment of Nanocrystal Aggregates into Single Crystals as a Result of Inherent Surface Stress

Crystallization by particle attachment is widely observed in both natural and synthetic environments. Although this form of nonclassical crystallization is generally described by oriented attachment, random aggregation of building blocks to give single‐crystal products is also observed, but the mechanism of crystallographic realignment is unknown. We herein reveal that random attachment during aggregation‐based growth initially produces a nonoriented growth front. Subsequent evolution of the orientation is driven by the inherent surface stress applied by the disordered surface layer and results in single‐crystal formation by grain‐boundary migration. This mechanism is corroborated by measurements of orientation rate versus external stress, which demonstrated a predictive relationship between the two. These findings advance our understandings about aggregation‐based growth via nanocrystal blocks and suggest an approach to material synthesis that takes advantage of stress‐induced coalignment.     

Interactions of ADP-stimulated human platelets with PEGylated polystyrene substrates prepared by surface amidation

A study primarily focused on the interactions between ADP-stimulated human platelets and PEGylated polystyrene substrates is described in this paper. The platelet–surface interactions were investigated using colorimetric acid phosphatase assay. Two types of amine-containing polymeric hydrogel materials based on poly(ethylene glycol) (PEG), H₂N–PEG–OCH₃ and H₂N–PEG–NH₂, were used to PEGylate polystyrene surfaces derivatized with maleic anhydride by amidation at alkaline pH. In addition, comparative studies using surfaces non-covalently adsorbed by bovine serum albumin (BSA) or fibrinogen (Fg) were also conducted. The assay results showed that no significant platelet adhesion was observed when PEGylated surfaces or BSA-coated surfaces were exposed to unstimulated gel-filtered platelets (GFP). However, upon ADP-stimulation, platelet adhesion to the surfaces under investigation in this study all increased to varying degrees. Most importantly, the results showed that polystyrene surfaces PEGylated using H₂N–PEG–NH₂ were most effective in resisting platelet adhesion when assays were performed using ADP-stimulated GFP. By PEGylating the surfaces of polystyrene microtiter wells via the amidation reaction described in this paper, it is demonstrated that (i) higher degree of surface PEGylation is favored at more alkaline pH and (ii) polystyrene substrates capable of more effectively resisting the adhesion of ADP-stimulated GFP can be obtained by the PEGylation reaction carried out at pH 9.1 using H₂N–PEG–NH₂.