Designing Molecular Printboards: A Photolithographic Platform for Recodable Surfaces

A light induced strategy for the design of β‐cyclodextrin (CD) based supramolecular devices is introduced, presenting a novel tool to fabricate multifunctional biointerfaces. Precision photolithography of a modified β‐CD was established on a light sensitive tetrazole surface immobilized on a bioinspired polydopamine (PDA) anchor layer via various shadow masks, as well as via direct laser writing (DLW), in order to craft any desired printboard design. Interfacial molecular recognition provided by light generated cavitate domains was demonstrated via spatially resolved encoding, erasing, and recoding of distinct supramolecular guest patterns. Thus, the light directed shaping of receptor monolayers introduces a powerful path to control supramolecular assemblies on various surfaces.     

Molecular Tweezers: Concepts and Applications

Taken to the molecular level, the concept of “tweezers” opens a rich and fascinating field at the convergence of molecular recognition, biomimetic chemistry and nanomachines. Composed of a spacer bridging two interaction sites, the behaviour of molecular tweezers is strongly influenced by the flexibility of their spacer. Operating through an “induced‐fit” recognition mechanism, flexible molecular tweezers select the conformation(s) most appropriate for substrate binding. Their adaptability allows them to be used in a variety of binding modes and they have found applications in chirality signalling. Rigid spacers, on the contrary, display a limited number of binding states, which lead to selective and strong substrate binding following a “lock and key” model. Exquisite selectivity may be expressed with substrates as varied as C₆₀, nanotubes and natural cofactors, and applications to molecular electronics and enzyme inhibition are emerging. At the crossroad between flexible and rigid spacers, stimulus‐responsive molecular tweezers controlled by ionic, redox or light triggers belong to the realm of molecular machines, and, applied to molecular tweezing, open doors to the selective binding, transport and release of their cargo. Applications to controlled drug delivery are already appearing. The past 30 years have seen the birth of molecular tweezers; the next many years to come will surely see them blooming in exciting applications.     

化学生物学中识别与组装的若干问题

化学与生物学的交叉与融合产生了新学科——化学生物学,开拓了化学和生物学研究的新领域,使人类得以从分子水平来阐释生命过程,揭示生命的奥秘。分子识别和组装是体系的构筑与功能集成的基础,也是自然界生物进行信息存贮、复制和传递的基础,以此来研究构筑具有特定生物学功能的超分子体系,对揭示生命现象和过程具有重要意义。本文结合我们的研究工作从（1）谷胱甘肽过氧化物酶(GPX)模拟与底物识别;（2）医用再生材料与活性支架;（3）类病毒颗粒的组装与解组装3个方面讨论了化学生物学中的识别与组装的意义。     

Rational Design and Synthesis of Optimized Glycoclusters for Multivalent Lectin–Carbohydrate Interactions: Influence of the Linker Arm

The design of multivalent glycoclusters requires the conjugation of biologically relevant carbohydrate epitopes functionalized with linker arms to multivalent core scaffolds. The multigram‐scale syntheses of three structurally modified triethyleneglycol analogues that incorporate amide moiety(ies) and/or a phenyl ring offer convenient access to a series of carbohydrate probes with different water solubilities and rigidities. Evaluation of flexibility and determination of preferred conformations were performed by conformational analysis. Conjugation of the azido‐functionalized carbohydrates with tetra‐propargylated core scaffolds afforded a library of 18 tetravalent glycoclusters, in high yields, by Cu^I‐catalyzed azide–alkyne cycloaddition (CuAAC). The compounds were evaluated for their ability to bind to PA‐IL (the LecA lectin from the opportunistic pathogen Pseudomonas aeruginosa). Biochemical evaluation through inhibition of hemagglutination assays (HIA), enzyme‐linked lectin assays (ELLA), surface plasmon resonance (SPR), and isothermal titration microcalorimetry (ITC) revealed improved and unprecedented affinities for one of the monovalent probes (K_d=5.8 μM ) and also for a number of the tetravalent compounds that provide several new nanomolar ligands for this tetrameric lectin.     

Nanoscale Structuring of Surfaces by Using Atomic Layer Deposition

Controlled structuring of surfaces is interesting for a wide variety of areas, including microelectronic device fabrication, optical devices, bio(sensing), (electro‐, photo)catalysis, batteries, solar cells, fuel cells, and sorption. A unique feature of atomic layer deposition (ALD) is the possibility to form conformal uniform coatings on arbitrarily shaped materials with controlled atomic‐scale thickness. In this Minireview, we discuss the potential of ALD for the nanoscale structuring of surfaces, highlighting its versatile application to structuring both planar substrates and powder materials. Recent progress in the application of ALD to porous substrates has even made the nanoscale structuring of high‐surface‐area materials now feasible, thereby enabling novel applications, such as those in the fields of catalysis and alternative energy.     

Towards Dynamic Control of Wettability by Using Functionalized Altitudinal Molecular Motors on Solid Surfaces

We report the synthesis of altitudinal molecular motors that contain functional groups in their rotor part. In an approach to achieve dynamic control over the properties of solid surfaces, a hydrophobic perfluorobutyl chain and a relatively hydrophilic cyano group were introduced to the rotor part of the motors. Molecular motors were attached to quartz surfaces by using interfacial 1,3‐dipolar cycloadditions. To test the effect of the functional groups on the rotary motion, photochemical and thermal isomerization studies of the motors were performed both in solution and when attached to the surface. We found that the substituents have no significant effect on the thermal and photochemical processes, and the functionalized motors preserved their rotary function both in solution and on a quartz surface. Preliminary results on the influence of the functional groups on surface wettability are also described.     

Self‐Assembly of Coiled Coils in Synthetic Biology: Inspiration and Progress

Biological self‐assembly is very complex and results in highly functional materials. In effect, it takes a bottom‐up approach using biomolecular building blocks of precisely defined shape, size, hydrophobicity, and spatial distribution of functionality. Inspired by, and drawing lessons from self‐assembly processes in nature, scientists are learning how to control the balance of many small forces to increase the complexity and functionality of self‐assembled nanomaterials. The coiled‐coil motif, a multipurpose building block commonly found in nature, has great potential in synthetic biology. In this review we examine the roles that the coiled‐coil peptide motif plays in self‐assembly in nature, and then summarize the advances that this has inspired in the creation of functional units, assemblies, and systems.     

Molecular scaffolds using multiple orthogonal conjugations: applications in chemical biology and drug discovery

Heteromultifunctional scaffolds that harness sequential "click" reactions will find significant utility in the areas of chemical biology and chemically enabled/enhanced biotherapeutics ("chemologics"). Here we review the existing synthetic technologies that illustrate the considerable potential of the field.     

Molecular Machines Working on Surfaces and at Interfaces

In the past ten years a great variety of artificial molecular machines have been constructed, and very interesting concepts for controlling molecular‐level movements by external inputs have been developed. Most of the studies, however, have been performed in solution, where the investigated systems contain a huge number of molecules which behave independently from one another because they cannot be addressed individually. Before such systems can find applications in many fields of technology, they must be interfaced with the macroscopic world by ordering them in some way so that they can behave coherently and can be addressed in space. The problem of obtaining ordered arrays of molecular machines can be addressed by a variety of techniques, which include deposition on surfaces, incorporation into polymers, organization at interfaces, and immobilization in membranes or porous materials. In the last few years, the development of scanning‐probe techniques has also enabled direct observation and manipulation of single molecular‐machine molecules on surfaces. Techniques of this kind have opened novel routes to the study of molecular machines, and have also contributed to better understanding the differences between movement at the macroscopic and molecular levels. This paper reviews some recent achievements in the field of molecular machines working on surfaces and at interfaces, as single molecules or ordered arrays. Hybrid natural–artificial machines are also discussed, and the working mechanism of some natural machines is illustrated for the purpose of comparison.     

Protein Adsorption on a Glycosylated Polyacrylonitrile Surface: Monitoring with QCM and SPR

A simple and efficient method to fabricate a glycosylated surface on a polyacrylonitrile‐based film is described. Construction and protein adsorption processes were monitored in situ using a QCM. A PANCHEMA film was deposited on the gold surface of the quartz crystal, and the glycosylated surface was then constructed through surface modification. Con A and BSA were used as probes to study the specificity of this surface to proteins. It can recognize Con A, while showing no specific interaction with BSA. The binding affinity indicates the presence of strong multivalent interactions between Con A and the glucose residues (cluster glycoside effect). Reproducibility and repeatability of the glycosylated polymer surface are sufficient to allow specific adsorption of Con A.

     

Chemical Imaging of Monolayers on Metal Surfaces: Applications in Corrosion,Catalysis, and Self‐Assembled Monolayers

In situ techniques are indispensable to understanding many topics in surface chemistry. As a consequence, several spectroscopic methods have been developed to provide molecular‐level information that only spectroscopy can supply. However, as important as this information is, it is just as critical to realize that nearly all surfaces under investigation have spatial heterogeneities of the order of nanometers to millimeters; thus, spatial analysis is very important to the overall interpretation. This Minireview focuses on a few of the recent developments in spectroscopic techniques that can provide spatial, spectroscopic, and in situ information. These techniques include photo‐electron microscopy, infrared and Raman imaging, and nonlinear optical imaging vibrational spectroscopy as applied to topics in corrosion, catalysis and self‐assembled monolayers.     

De Novo Fragment Design for Drug Discovery and Chemical Biology

Automated molecular de novo design led to the discovery of an innovative inhibitor of death‐associated protein kinase 3 (DAPK3). An unprecedented crystal structure of the inactive DAPK3 homodimer shows the fragment‐like hit bound to the ATP pocket. Target prediction software based on machine learning models correctly identified additional macromolecular targets of the computationally designed compound and the structurally related marketed drug azosemide. The study validates computational de novo design as a prime method for generating chemical probes and starting points for drug discovery.     

Molecular aggregation within self-ordered monolayers.

The monolayer growth of pyrimido-pentaphenylbenzene (NPB) on Cu(111) is investigated by means of low-temperature scanning tunneling microscopy (LT-STM). The pyrimidine side group gives rise to a pronounced resonant tunneling state and, furthermore, affects molecular self-ordering. Different molecular aggregates are formed inside the hexagonal closed packed monolayer. A structure model for the monolayer is proposed and the temperature dependence of this self-ordering process is investigated by varying the preparation temperature between 270 and 370 K. The intermolecular bonding of the aggregates is demonstrated by STM manipulation experiments. Moreover, different aggregations of the molecules induce characteristic energy shifts in the resonant tunneling state, as revealed by means of scanning tunneling spectroscopy.     

核酸的有机化学研究在分子生物学发展中的作用

本文主要综述有机化学在建立核酸的顺序测定法和自动顺序仪,在破译遗传密码,在建立核酸片段的化学合成方法,固相合成法及DNA合成仪的设计,在合成许多有生物活力的核酸分子,在发展并完善遗传工程以及新近发现酶RNA(Ribozyme)等方面的卓越贡献。最后简要地展望有机化学将对生物学发展作出进一步贡献的几个方面。     

Towards Design Rules for Covalent Nanostructures on Metal Surfaces

The covalent molecular assembly on metal surfaces is explored, outlining the different types of applicable reactions. Density functional calculations for on‐surface reactions are shown to yield valuable insights into specific reaction mechanisms and trends across the periodic table. Finally, it is shown how design rules could be derived for nanostructures on metal surfaces.