Guest Binding Drives Host Redistribution in Libraries of CoII4L4 Cages

Two Co^II₄L₄ tetrahedral cages prepared from similar building blocks showed contrasting host–guest properties. One cage did not bind guests, whereas the second encapsulated a series of anions, due to electronic and geometric effects. When the building blocks of both cages were present during self‐assembly, a library of five Co^II L^A _x L^B _4?x cages was formed in a statistical ratio in the absence of guests. Upon incorporation of anions able to interact preferentially with some library members, the products obtained were redistributed in favor of the best anion binders. To quantify the magnitudes of these templation effects, ESI‐MS was used to gauge the effect of each template upon library redistribution.     

Selective Recognition of Amino Acids and Peptides by Small Supramolecular Receptors

To this day, the recognition and high affinity binding of biomolecules in water by synthetic receptors remains challenging, while the necessity for systems for their sensing, transport and modulation persists. This problematic is prevalent for the recognition of peptides, which not only have key roles in many biochemical pathways, as well as having pharmacological and biotechnological applications, but also frequently serve as models for the study of proteins. Taking inspiration in nature and on the interactions that occur between several receptors and peptide sequences, many researchers have developed and applied a variety of different synthetic receptors, as is the case of macrocyclic compounds, molecular imprinted polymers, organometallic cages, among others, to bind amino acids, small peptides and proteins. In this critical review, we present and discuss selected examples of synthetic receptors for amino acids and peptides, with a greater focus on supramolecular receptors, which show great promise for the selective recognition of these biomolecules in physiological conditions. We decided to focus preferentially on small synthetic receptors (leaving out of this review high molecular weight polymeric systems) for which more detailed and accurate molecular level information regarding the main structural and thermodynamic features of the receptor biomolecule assemblies is available.     

Synthesis of alpha-(2-->5)Neu5Gc oligomers

A facile synthesis of the sialic acid oligomers alpha-(2-->5)Neu5Gc (1) is presented. Monosaccharides 2-4 with suitable functionality were used as the building blocks. After selective removal of the paired carboxyl and amine protecting groups, the fully protected oligomers were assembled through consecutive coupling of the building blocks by well established peptide coupling techniques. By this approach, fully protected oligomers as large as an octasaccharide were synthesized. Deprotection of these fully protected oligomers was conducted in two steps (LiCl in refluxing pyridine and 0.1 n NaOH) to afford the desired products in high yield. Enzymatic degradation of the octamer with neuraminidase, monitored by capillary electrophoresis (CE), was also accomplished. The stepwise exo-cleavage adducts were all well separated and identified in the CE spectrum. The strategy described here for solution-phase synthesis also provides the basis for future solid-phase synthesis of poly-alpha-(2-->5)Neu5Gc.     

Post-Synthesis Conversion of an Unstable Imine Cage to a Stable Cage with Amide Moieties Towards Selective Receptor for Fluoride

Synthesis of robust covalent macrocycles/cages via multiple amide-bond forming reaction is highly challenging and generally it needs multistep reactions. One-pot reaction of appropriate di-/tri-acyl chloride with a diamine generally results polymers or oligomers instead of discrete architectures. To overcome this limitation, a strategy is reported here using dynamic imine chemistry for facile construction of imine-based macrocycle and cage upon treatment of a diamine with di- and tri-aldehydes respectively, followed by post-synthesis one-step conversion of imine bonds to amides to form the desired robust macrocycle and cage containing multiple amide bonds. While the macrocycle was found to form aggregates in DMSO, the cage was intact without any aggregation. Six amide groups in the confined pocket of the cage made it an ideal receptor for selective binding of fluoride with very high selectivity (∼3 10³ fold) over chloride, and it was silent towards other halides, phosphate, and other oxyanions.     

Calix[4]arene-Based Triple-Stranded Metallohelicate in Water

The title complex is a triple-stranded metallohelicate organized by the self-assembly of 5,17-difunctionalized calix[4]arenes and metal cations with octahedral coordination geometry. Due to hydrophilic triethylene glycol chains on the lower rim of the calix[4]arene, the metallohelicate can encapsulate cationic guests in water. NMR and UV-vis titration experiments reveal that the metallohelicate captures a pyridinium guest with an alanine derivative to form a host-guest complex with a host-guest ratio of 1 : 1. CD spectroscopy confirms the bias of the P- and M-helical sense of the metallohelicate by the captured guest. The metallohelicate captures two molecules of dicationic N,N’-dimethyl-DABCO and monocationic N-methyl quinuclidine, exhibiting a positive allosteric effect. ¹H NMR titration experiments indicate that the bound guests are in close proximately to the aromatic rings of the ligands. Molecular mechanics calculations based on the UV-vis and NMR observations suggest that the first guest preorganizes the conformation of the metallohelicate to facilitate access of the second guest to the cavity.     

Synthesis and Biological Evaluation of Several Dephosphonated Analogues of CMP‐Neu5Ac as Inhibitors of GM3‐Synthase

Previous studies demonstrated that reducing the GM3 content in myoblasts increased the cell resistance to hypoxic stress, suggesting that a pharmacological inhibition of the GM3 synthesis could be instrumental for the development of new treatments for ischemic diseases. Herein, the synthesis of several dephosphonated CMP‐Neu5Ac congeners and their anti ‐ GM3‐synthase activity is reported. Biological activity testes revealed that some inhibitors almost completely blocked the GM3‐synthase activity in vitro and reduced the GM3 content in living embryonic kidney 293A cells, eventually activating the epidermal growth factor receptor (EGFR) signaling cascade.     

Synthesis of Electron‐Deficient Corona[5]arenes and Their Selective Complexation with Dihydrogen Phosphate: Cooperative Effects of Anion–π Interactions

Reported here are the syntheses, conformational structures, electrochemical properties, and noncovalent anion binding of corona[5]arenes. A (3+2) fragment coupling reaction proceeded efficiently under mild reaction conditions to produce a number of novel heteroatom‐ and methylene‐bridged corona[3]arene[2]tetrazine macrocycles. Selective oxidation of the sulfur atom between two phenylene rings afforded sulfoxide‐ and sulfone‐linked corona[5]arenes in good yields. All corona[5]arenes synthesized adopted similar 1,2,4‐alternate conformational structures, forming pentagonal cavities. The cavity sizes and the electronic properties such as redox potentials, were measured with CV and DPV, and were influenced by the different bridging units. As electron‐deficient macrocycles, the acquired corona[3]arene[2]tetrazines served as highly selective hosts, forming complexes with the hydrogen‐bonded dimer of dihydrogen phosphate through cooperative anion–π interactions.     

Selective Binding of Dopamine and Epinephrine in Water by Molecularly Imprinted Fluorescent Receptors

Catecholamines play important roles in biology but their structural similarity makes it challenging to construct synthetic receptors with selective binding. A combination of covalent and noncovalent binding groups in the hydrophobic core of water‐soluble nanoparticles enabled them to recognize dopamine and epinephrine with an association constant (K_a) of 3–4×10⁴ M^?1 in water, an order of magnitude higher than those of previously reported synthetic hosts. In addition, minute structural changes among analogues were detected including the addition or removal of a single hydroxyl or methyl group.     

Self-assembly of Pd4L2 Supramolecular Cage and Permanganate Anion Adsorption Behavior in Water

Journal of Cluster Science - A novel metal–organic cage 1·8PF6? was precisely self-assembled using polynitrogen pyrazine-triazine ligand as linker L1 and bpyPd(NO3)2 as...     

A Chemically Fuelled Molecular Automaton Displaying Programmed Migration of Zn2+ Between Alternative Binding Sites

A molecular system comprising a cationic zinc complex and an amino acid-derived ambident ligand having phosphate and carboxylate binding sites undergoes a series of rearrangements in which the metal cation migrates autonomously from one site to another. The location of the metal is identified by the circular dichroism spectrum of a ligated bis(2-quinolylmethyl)-(2-pyridylmethyl)amine (BQPA) chromophore, which takes a characteristic shape at each binding site. Migration is fuelled by the decomposition of trichloroacetic acid to CO₂ and CHCl₃, which progressively neutralises the acidity of the system as a function of time, revealing in sequence binding sites of increasing basicity. The migration rate responds to control by variation of the temperature, water content and triethylamine concentration, while an excess of fuel controls the duration of an induction period before the migration event.     

一种能选择性识别磷酸根离子的金属配合物化学敏感器

合成了两种Schiff碱类金属配合物1([Cu(L1)]²⁺)和2([Cu(L2)]²⁺).对它们在强极性溶剂,如[V(水):V(乙醇)=98:2]混合溶剂中与阴离子间的相互作用进行了研究.发现具有C_3v结构的配合物1有着优良的检测PO₄^3-离子的能力.通过UV光谱滴定实验,表明配合物1和PO₄^3-间形成了1:1的稳定配合物.配合物1对HPO₄^2-也有一定的响应性.但对其它的阴离子(如四面体和非四面体结构的阴离子)物种,则未观察到有任何响应.文中还提出了配合物1与阴离子间构成新的配合物可能结构的建议.但是对于配合物2,对阴离子的响应能力比较差.对于实验结果以及如何提高敏感器化合物的选择能力进行了初步讨论.     

药物头孢氨苄分子模板聚合物水中结合性质的研究

采用分子模板技术合成了以头孢氨苄为模板分子以三氟甲基丙烯酸和４－乙烯基吡啶同时为功能单体的分子模板聚合物。将得到的棒状聚合物研磨过筛后,运用平衡结合实验研究了头孢氨苄分子模板聚合物的结合性质,Ｓｃａｔｃｈａｒｄ分析表明,在所研究的浓度范围内,在聚合物中形成了两类不同的结合位点。头孢氨苄分子模板聚合物与其化学组成相同的非模板聚合物相比,有很高的结合容量。底物选择性实验表明,与其它结构相似的药物相比,     

Construction of Photo-Responsive Pd2L4-Type Nanocages based on Feringa's Second-Generation Motor and Its Guest Binding Ability for C60

We present the construction of a M₂L₄-type metal-organic nanocage featuring four endohedral Feringa's motor motifs and its adaptive encapsulation towards a C₆₀ guest molecule. The structure of the cage, though complicated on the ¹H NMR spectrum due to the adoption of mixed ligands, was unambiguously characterized with a combination of ESI-MS, 2D DOSY, ¹³C NMR and particularly the SAXS technique. The molecular motor within the cage demonstrated similar photophysical properties to the uncoordinated one, indicating the motor's function was not compromised when it was anchored in such a confined nanospace. Furthermore, the nanocage showed good guest encapsulation ability towards C₆₀, and a guest induced-fit behavior of the cage was revealed based on the extensive SAXS analysis and molecular dynamics simulation. The adaptive motorized nanocage reported here represents one of the very few examples of integrating individual motors into a discrete nanoconfined system and offers prospects to achieve its non-equilibrium functions.     

Highly Selective Binding and Inhibition of Pyr-His-Pro-NH2 (TRH) Function using a Polypyridinyl Macrocyclic Receptor with an Amphiphilic Cavity

Macrocycle, cyclo[4] [(1,3-(4,6)-dimethylbezene)[4](2,6-(3,5)-dimethylpyridine ( B4P4 ), shows highly selective binding affinity with protirelin (Pyr-His-Pro-NH₂; TRH) among the tested 26 drug or drug adductive substrates. The stable complexation in a 1:1 manner was fully characterized in solution, gas phase, and solid state study. Furthermore, B4P4 acts as an efficient TRH inhibitor even at [macrocycle]:[drug] <1:300, both in membrane transport and cellar incubation. The current work provides an unprecedented strategy for macrocycles to be efficiently used in drug target therapy.     

Selective Binding Thermodynamics of Bile Acids by Oligo (ethylenediamino)-β-Cyclodextrins and Their Copper (II) Complexes

Complex stability constants (K _S), standard molar enthalpy changes (ΔH°) and entropy changes (TΔS°) for the inclusion complexation of native β-cyclodextrin (β-CD) (1) and some modified β-CDs, i.e., mono(6-ethylenediamino-6-deoxy)-β-CD (3), mono[6-diethylenetriamino-6-deoxy]-β-CD (4) and their corresponding copper complexes 5 and 6, with four representative bile acid guests, i.e., cholate (CA), deoxycholate (DCA), glycocholate (GCA) and taurocholate (TCA), were determined at 25 °C in aqueous phosphate buffer solution (pH 7.20) by means of isothermal titration microcalorimetry (ITC). The stoichiometry of resulting inclusion complexes between CDs and bile acids was demonstrated by UV and conductivity as well as ITC experiments, showing 1:1 binding model upon all inclusion complexation except for metal-mediated dimer 5. The complex stability constants for modified β-CD 2–4 are dramatically magnified with the extended length of amino tether. As compared with 3 and 4, copper(II) complexes 5 and 6 significantly enhance not only binding ability but also molecular selectivity toward bile guest molecule CA through multipoint recognition, but decreased complexes stability toward TCA could be attributed to the decreased hydrophobic microenvironment of CDs cavity due to the introduction of copper(II) coordination center. Thermodynamically, the resulting complexes between hosts and bile guests are driven absolutely by enthalpy, accompanied by entropy gain or loss. Using the present data and those previously reported for mono(6-amino-6-deoxy)-β-CD (2), thermodynamic behavior and enhanced molecular selectivity could be discussed from the viewpoint of hydrophobic interactions, electrostatic cooperation and van der Waals between the hosts and guests.     

Optical, Electrochemical, and Catalytic Properties of the Unsaturated Host Pd3(dppm)3(CO)2+ and Pd4(dppm)4(H)2+ 2 Clusters: An Overview

This paper presents an overview of the optical, photophysical, and photochemical properties including UV-visible and luminescence spectra in solution at 298 and 77 K, along with electrochemical, and catalytic behavior under reduction conditions (for both thermally and electrochemically assisted systems) of the tri- and tetranuclear Pd₃(dppm)₃(CO)²⁺ and Pd₄(dppm)₄(H)²⁺ ₂ clusters (dppm=bis(diphenylphosphino)methane). This review is also complemented with relevant information about their syntheses, molecular and electronic structures supported from computer modeling, EHMO and DFT calculations, and their host-guest behavior with anions and neutral molecules, in relation with their observed reactivity.     

Selective synthesis of Neu5Ac2en and its oxazoline derivative using BF3·Et2O

Application of the Lewis acid BF₃·Et₂O to the selective synthesis of 5-acetamido-2,6-anhydro-3,5-dideoxy-d-glycero-d-galacto-non-2-enonic acid (Neu5Ac2en) and the related oxazoline, methyl 7,8,9-tri-O-acetyl-2,3,4,5-tetradeoxy-2,3-didehydro-2,3-trideoxy-4′,5′-dihydro-2′-methyloxazolo[5,4-d]- d-glycero-d-talo-non-2-enonate is described.     

Peripheral Templation‐Modulated Interconversion between an A4L6 Tetrahedral Anion Cage and A2L3 Triple Helicate with Guest Capture/Release

An anion‐coordination‐based A₄L₆ (“A” denotes anion and “L” is ligand) tetrahedral cage was constructed by a C₂‐symmetric bis‐bis(urea) ligand and phosphate anion, which showed reversible interconversion with the A₂L₃ triple helicate as a response to the template, concentration, or solvent. Notably, an unusual “peripheral” templation was found to be critical to stabilize the tetrahedral structure. This peripheral effect was utilized to assemble an “empty” A₄L₆ cage that allows the multi‐stimuli‐controlled capture/release of biologically important species such as choline and acetylcholine.