“Preorganized” ligand

Structural fixation of a ligand in its bioactive conformation may, due to entropic reasons, improve affinity. We present a congeneric series of thrombin ligands with a variety of functional groups triggering preorganization prior to binding. Fixation in solution and complex formation have been characterized by crystallography, ITC and MD simulations. First, we show why these preorganizing modifications do not affect the overall binding mode and how key interactions are preserved. Next, we demonstrate how preorganization thermodynamics can be largely dominated by enthalpy, rather than entropy due to the significant population of low-energy conformations...

Photoinduced electron and energy transfer through preorganized chromophore, donor, and acceptor arrays are key to light-harvesting capabilities of photosynthetic plants and bacteria. Mimicking the design principles of natural photosystems, we constructed a new luminescent pillared paddle wheel metal-organic framework (MOF), Zn2 (NDC)2 (DPTTZ), featuring naphthalene dicarboxylate (NDC) struts that served as antenna chromophores and energy donors and N , N' -di(4-pyridyl)thiazolo-[5,4- d ]thiazole (DPTTZ) pillars as complementary energy acceptors and light emitters...

Macrocyclization can improve bioactive peptide ligands through preorganization of molecular topology, leading to improvement of pharmacologic properties like binding affinity, cell permeability and metabolic stability. Here we demonstrate that Diels-Alder [4+2] cy-cloadditions can be harnessed for peptide macrocyclization and stabilization within a range of peptide scaffolds and chemical environ-ments. Diels-Alder cyclization of diverse diene-dienophile reactive pairs proceeds rapidly, in high yield and with tunable stereochemical preferences on solid-phase or in aqueous solution...

The precise arrangement of metal ions in type and number by a ligand represents an important challenge in biology as well as in materials science. The preorganization of different metal ions such as alkaline-earth and transition-metal ions is of particular interest for the design of catalysts or precursors of oxides. This study is based on a Ω-shaped salen-derived ligand comprising N2 O2 and O2 O2 coordination sites. The selective binding of Cu(II) and Ni(II) and alkaline-earth-metal ions is influenced by many factors such as the size of the cation, the solvent, or the counterion...

Pillararenes are macrocyclic oligomers of alkoxybenzene akin to calixarenes but tethered at the 2,5-positions via methylene bridges. Benefiting from their unique pillar-shaped architecture favorable for diverse functionalization and versatile host-guest properties, pillararenes decorated with chelating groups worked excellently as supporting platforms to construct extractants or adsorbents for metal ion separation. This feature article provides a detailed summary of pillararenes in Ln/An separation by liquid-liquid extraction and heavy metal separation by solid-liquid extraction...

The synthesis and characterization of two novel symmetric triazine-ring opening ligands CA-MP (pyridine derivative)/CA-BOPhen (1,10-phenanthroline derivative) functionalized SiO2 -P (P = Polymer) adsorbents for separation of Pd(II) from HNO3 solutions are presented. SEM, N2 adsorption/desorption isotherms, TGA and EDS spectroscopy characterization results showed that CA-MP and CA-BOPhen were successfully introduced into the pores of SiO2 -P carrier via physical intermolecular interactions. CA-MP@SiO2 -P and CA-BOPhen@SiO2 -P show high efficiency, high selectivity, extremely fast adsorption rates towards Pd(II) over 19 typical fission or corrosion products in HNO3 solution...

Unraveling the function of biological copper (Cu) requires tools that can selectively recognize and manipulate this trace nutrient within the complex chemical environment of biological systems. Increasing evidence suggests that cells maintain an exchangeable pool of Cu(I) that is buffered in the high zeptomolar to low attomolar range. While mixed amine-thioether donors have been commonly employed for the design of Cu(I)-selective ligands and probes, their dissociation constants are limited to the pico- to femtomolar range...

The KEAP1-NRF2-mediated cytoprotective response plays a key role in cellular homoeostasis. Insufficient NRF2 signaling during chronic oxidative stress may be associated with the pathophysiology of several diseases with an inflammatory component, and pathway activation through direct modulation of the KEAP1-NRF2 protein-protein interaction is being increasingly explored as a potential therapeutic strategy. Nevertheless, the physicochemical nature of the KEAP1-NRF2 interface suggests that achieving high affinity for a cell-penetrant druglike inhibitor might be challenging...

Four imidazoles, serving as metalloprotein-inspired ligands for complexing a range of transition metal cations, were incorporated into tetramolecular G-quadruplex DNA structures. Modified quadruplexes were found to complex Cu(ii), Ni(ii), Zn(ii) and Co(ii) in a 1 : 1 ratio with unprecedented strong thermal stabilizations of up to Δ T 1/2 = +51 °C. Furthermore, addition of Cu(ii) was found to lead to extraordinarily fast G-quadruplex association rates with k on values being ∼100 times higher compared to unmodified G-quadruplexes...

Due to the ever-increasing demand for high purity individual rare earth elements, novel and highly selective separation processes are increasingly sought after. Herein, we report a separation protocol that employs shape-persistent 2,9-bis-lactam-1,10-phenanthroline (BLPhen) ligands exhibiting unparalleled selectivity for light trivalent lanthanides. The highly preorganized binding pocket of the ligand allows separation of lanthanides with high fidelity, even in the presence of competing transition metals, in a biphasic separation system...

Inspired by natural photosynthesis, researchers have designed symmetric metal-organic hosts with large inner pockets that are spontaneously generated through preorganized ligands and functionalized metallocorners to construct dye-containing host-guest systems. The abundant noncovalent interaction sites in the pockets of the hosts facilitated substrate-catalyst interactions for possible enrichment, fixation, and activation of substrates/reagents, providing special electron transfer pathways for regio- or stereoselectively photocatalytic chemical transformations...

Pyridylpyrazole ligands have shown excellent competence for partitioning actinides from lanthanides. As far as we know, the preorganization structure of the ligand has a great impact on the extraction separation ability. However, the mechanism that works well for some ligands but fails for others needs to be clearly elucidated. In this work, we designed three various pyridylpyrazole ligands, BPP, BPBP, and BPPhen, and further preorganized one or both side pyrazole rings of these ligands. The properties of these ligands and the coordination structures, bonding nature and thermodynamic behaviors of the related Am(III) and Eu(III) complexes have been systematically studied in a theoretical fashion...

Calorimetric studies of protein-ligand binding sometimes yield thermodynamic data that are difficult to understand. Today, molecular simulations can be used to seek insight into such calorimetric puzzles, and, when simulations and experiments diverge, the results can usefully motivate further improvements in computational methods. Here, we apply near-millisecond duration simulations to estimate the relative binding enthalpies of four peptidic ligands with the Grb2 SH2 domain. The ligands fall into matched pairs, where one member of each pair has an added bond that preorganizes the ligand for binding and thus may be expected to favor binding entropically, due to a smaller loss in configurational entropy...

Over the last two decades, interlocked molecular species have received considerable attention, not only because of their intriguing structures and topological importance, but also because of their potential applications as smart materials, nanoscale devices, and molecular machines. Through judicious choice of metal centers and their adjoining ligands, a range of interesting interlocked structures have been realized by coordination-driven self-assembly. In addition, researchers have extensively developed synthetic methodologies for the construction of organized self-assemblies...

Very rigid tetra-, penta-, hexa-, hepta- and octadentate bispidine ligands are well preorganized for specific coordination geometries. The broad range of coordination numbers, geometries and donor sets allows one to design and prepare bispidines for many specific metal ions and applications. Major requirements for radiopharmaceuticals are efficient labeling, inertness under physiological conditions and easy functionalization of the ligands with biological vectors. The reasons why bispidines are among the most favorable chelators for radiopharmaceutical applications, a comprehensive list of bispidine ligands and a range of examples where bispidines have been used to develop radiopharmaceuticals for future applications in diagnosis and therapy are discussed...

The large yybP-ykoY family of bacterial riboswitches is broadly distributed phylogenetically. Previously, these gene-regulatory RNAs were proposed to respond to Mn2+ . X-ray crystallography revealed a binuclear cation-binding pocket. This comprises one hexacoordinate site, with six oxygen ligands, which preorganizes the second, with five oxygen and one nitrogen ligands. The relatively soft nitrogen ligand was proposed to confer affinity for Mn2+ , but how this excludes other soft cations remained enigmatic...

Two macrocyclic tetralactam receptors are shown to selectively encapsulate anionic, square-planar chloride and bromide coordination complexes of gold(III), platinum(II), and palladium(II). Both receptors have a preorganized structure that is complementary to its precious metal guest. The receptors do not directly ligate the guest metal center but instead provide an array of arene π-electron donors that interact with the electropositive metal and hydrogen-bond donors that interact with the outer electronegative ligands...

A series of polynuclear assemblies based on ligand L (1,4,7-tris[hydrogen (6-methylpyridin-2-yl)phosphonate]-1,4,7-triazacyclononane) has been developed. The coordination properties of ligand L with LnIII (Ln = La, Eu, Tb, Yb, Lu) have been studied in water (pH = 7.0) and in D2 O (pD = 7.0) by UV-absorption spectrometry, spectrofluorimetry, 1 H and 31 P NMR, DOSY, ESI-mass spectrometry, and X-ray diffraction. This nonadentate ligand forms highly stable mononuclear complexes in water and provides a very efficient shielding of the Ln cations, as emphasized by the very good luminescence properties of the Yb complex in D2 O, especially regarding its lifetime (τD2 O = 10...

The hydroformylation reaction is one of the most intensively explored reactions in the field of homogeneous transition metal catalysis, and many industrial applications are known. However, this atom economical reaction has not been used to its full potential, as many selectivity issues have not been solved. Traditionally, the selectivity is controlled by the ligand that is coordinated to the active metal center. Recently, supramolecular strategies have been demonstrated to provide powerful complementary tools to control activity and selectivity in hydroformylation reactions...

The complex formation of the following diazaperylene ligands (L) 1,12-diazaperylene 1, 1,1'-bisisoquinoline 2, 2,11-disubstituted 1,12-diazaperylenes (alkyl = methyl, ethyl, isopropyl, 3, 5, 7), 3,3'-disubstituted 1,1'-bisisoquinoline (alkyl = methyl, ethyl, isopropyl, 4, 6, 8 and with R = phenyl, 11 and with pyridine 12), and the 5,8-dimethoxy-substituted diazaperylene 9, 6,6'-dimethoxy-substituted bisisoquinoline 10 with AgBF4 was investigated. Collision-induced dissociation measurements were used to evaluate the relative stabilities of the ligands themselves and for the [1:1]+ complexes as well as for the homoleptic and heteroleptic silver [1:2]+ complexes in the gas phase...