Molecular Self-recognition Research Articles

Stereocontrol of Metal-Centred Chirality in Rhodium(III) and Ruthenium(II) Complexes with N2N'P Ligand.

Rh(III) and Ru(II) complexes, [RhCl2(κ4-N2N'P-L)][SbF6] (1) and [RuCl2(κ4-N2N'P-L)] (2), were synthesised using the tetradentate ligand L (L=N,N-bis[(pyridin-2-yl)methyl]-[2-(diphenylphosphino)phenyl]methanamine). In each case only one diastereomer is detected, featuring cis-disposed pyridine groups. The chloride ligand trans to pyridine can be selectively abstracted by AgSbF6, with the ruthenium complex (2) reacting more readily at room temperature compared to the rhodium complex (1) which requires elevated temperatures. Rhodium complexes avoid the second chloride abstraction, whereas ruthenium complexes can form the chiral bisacetonitrile complex [Ru(κ4-N2N'P-L)(NCMe)2][SbF6]2 (5) upon corresponding treatment with AgSbF6. The complex [RhCl2(κ4-N2N'P-L)][SbF6] (1) has also been used to synthesise polymetallic species, such as the tetrametallic complex [{RhCl2(κ4-N2N'P-L)}2(μ-Ag)2][SbF6]4 (6) which was formed with complete diastereoselectivity and chiral molecular self-recognition. In addition, a stable bimetallic mixed-valence complex [{Rh(κ4-N2N'P-L)}{Rh(COD)}(μ-Cl)2][SbF6]2 (7) (COD=cyclooctadiene) was synthesised. These results highlight the significant differences in chloride lability between Rh3+ and Ru2+ complexes and demonstrate the potential for complexes to act as catalyst precursors and ligands in further chemistry applications.

Co-assembly of a multicomponent network of nanofiber-wrapped nanotubes.

Strategies to create organized multicomponent nanostructures composed of discrete, self-sorted domains are important for developing materials that mimic the complexity and multifunctionality found in biological systems. These structures can be challenging to achieve due to the required balance of molecular self-recognition and supramolecular attraction needed between the components. Herein, we report a strategy to construct a two-component nanostructure via a hierarchical assembly process whereby two monomeric building blocks undergo self-sorting assembly at the molecular level followed by a supramolecular association to form a nanofiber-wrapped nanotube. The two molecules self-sorted into respective nanofiber and nanotube assemblies, yet assembly of the nanofibers in the presence of the nanotube template allowed for directed integration into a hierarchical multilayer structure via electrostatic interactions. The fiber-wrapped nanotube co-assembly was characterized using transmission electron microscopy (TEM), atomic force microscopy (AFM) and Förster resonance energy transfer (FRET) between the components. Strategies to co-assemble multicomponent nanostructures composed of discrete, spatially sorted domains with controllable higher level interactions will be critical for the development of novel, functionally competent nanomaterials.

Biomolecular interfaces based on self-assembly and self-recognition form biosensors capable of recording molecular binding and release.

This research proposed to create the next generation of versatile electrochemical-based biosensors capable of monitoring target capture and release as dictated by molecular binding or unbinding. The biosensor integrates cellular machines (i.e., microtubules, structural elements of cells and kinesin molecular motors involved in cellular transport) as functional units; its assembly is based on molecular self-assembly and self-recognition. Our results demonstrate that the designed biosensor was capable of allowing detection of binding and unbinding events based on redox reactions at user-controlled electrode interfaces. The analysis also showed that the sensitivity of the designed biosensor or its ability to record such events could be user-controlled at any given time by adjusting the energy source that "fuels" the system.

Monitoring the hydrogen bond net configuration and the dimensionality of aniline and phenyloxamate by adding 1H-pyrazole and isoxazole as substituents for molecular self-recognition

Monitoring the hydrogen bond and dimensionality of aniline and phenyloxamate by adding 1H-pyrazole/isoxazole for molecular self-recognition.

The Stepwise Reaction of Rhodium and Iridium Complexes of Formula [MCl2 (κ4 C,N,N',P-L)] with Silver Cations: A Case of trans-Influence and Chiral Self-Recognition.

Acetonitrile suspensions of the dichlorido complexes [MCl2 (κ4 C,N,N',P-L)] [M=Rh (1), Ir (2)] react with AgSbF6 in a 1:2 molar ratio affording the bis-acetonitrile complexes [M(κ4 C,N,N',P-L)(NCMe)2 ][SbF6 ]2 (3 and 4). The reaction takes place in a sequential manner and the intermediates can be isolated varying the M:Ag molar ratio. In a 2:1 molar ratio, it affords the dimetallic monochlorido-bridged compounds [{MCl(κ4 C,N,N',P-L)}2 (μ-Cl)][SbF6 ] (5 and 6). In a 1:1 molar ratio, the monosubstituted solvato-complexes [MCl(κ4 C,N,N',P-L)(Solv)][SbF6 ] (Solv=H2 O, MeCN, 7-10) were obtained. Finally, in a 2:3 molar ratio, it gives complexes 11 and 12 of formula [{M(κ4 C,N,N',P-L)(NCMe)(μ-Cl)}2 Ag][SbF6 ]3 in which a silver cation joints two cationic monosubstituted acetonitrile-complexes [MCl(κ4 C,N,N',P-L)(NCMe)]+ through the remaining chlorido ligands and two Ag⋅⋅⋅C interactions with one of the phenyl rings of each PPh2 group. In all the complexes, the aminic nitrogen and the central metal atom are stereogenic centers. In the trimetallic complexes 11 and 12, the silver atom is also a stereogenic center. The formation of the cation of the dimetallic complexes 5 and 6, as well as that of the trimetallic complexes 11 and 12, takes place with chiral molecular self-recognition. Experimental data and DFT calculations provide plausible explanations for the observed molecular recognition. The new complexes have been characterized by analytical, spectroscopic means and by X-ray diffraction methods.

Molecular self-recognition: a chiral [Mn(II)6] wheel via donor-acceptor π···π contacts and H-bonds.

A multinucleating ligand capable of establishing different types of intermolecular interactions, when combined with acetate groups leads to the assembly of a chiral [Mn(II)3] cluster poised for a process of self-recognition through a combination of perfectly complementary weak forces.

Dscam and DSCAM: complex genes in simple animals, complex animals yet simple genes

Cadherins and the immunoglobulin (Ig) proteins give rise to a multitude of surface receptors, which function as diverse cell adhesion molecules (CAMs) or signal-transducing receptors. These functions are often interdependent, and rely on a high degree of specificity in homophilic binding as well as heterophilic interactions. The Drosophila receptor Dscam is an exceptional example of homophilic binding specificity involved in a number of important biological processes, such as neural wiring and innate immunity. Combinatorial use of alternatively spliced Ig-domains enables the generation of an estimated 18,000 isoform-specific homophilic receptor pairs. Although isoform diversity of Dscam is unique to arthropods, recent genetic analysis of vertebrate DSCAM (Down Syndrome Cell Adhesion Molecule) genes has revealed an intriguing conservation of molecular functions underlying neural wiring. This review covers the multiple functions of Dscam across different species highlighting its remarkable versatility as well as its conserved basic functions in neural development. We discuss how an unprecedented expansion of complex alternative splicing has been uniquely employed by arthropods to generate diverse surface receptors, important for cell-cell communication, molecular self-recognition in neurons, and innate immune defenses. We end with a speculative hypothesis reconciling the striking differences in Dscam and DSCAM gene structures with their conserved functions in molecular recognition underlying neural circuit formation.

Edge‐to‐Face CH/π Aromatic Interaction and Molecular Self‐Recognition in epi‐Cinchona‐Based Bifunctional Thiourea Organocatalysis

The impact of cooperativity between intermolecular interactions is demonstrated by the molecular self-recognition properties of highly enantioselective epi-cinchona bifunctional thiourea organocatalysts. Low-temperature NMR experiments in inert solvents have revealed two sets of nonequivalent resonances in equal population for thiourea-modified members of the epi-quinine and epi-quinidine families. In solution, the predominance of an asymmetric (C1) dimeric self-assembly with noteworthy structural motifs became evident: simultaneous intra- and intermolecular thiourea hydrogen bonding and a CH/pi interaction were observed. Both the stereochemical and the diverse conformational features of the system favor the observed quinoline T-shaped aromatic pi-pi stacking interaction. The structure findings are supported by quantitative proton-proton distance data that were available from NOE buildup curves. The 3D structure of the dimeric assembly has been modeled in agreement with the H-H distance restraints. Owing to the geometrical preference associated with the dimerization process, the self-assembled bifunctional system is interpreted as a charge-transfer complex with the potential for catalyst self-activation.

Self-recognition and self-selection in multicomponent supramolecular coordination networks on surfaces

Self-recognition, self-selection, and dynamic self-organization are of fundamental importance for the assembly of all supramolecular systems, but molecular-level information is not generally accessible. We present direct examples of these critical steps by using scanning tunneling microscopy to study mixtures of complementary organic ligands on a copper substrate. The ligands coordinate cooperatively with iron atoms to form well ordered arrays of rectangular multicomponent compartments whose size and shape can be deliberately tuned by selecting ligands of desired length from complementary ligand families. We demonstrate explicitly that highly ordered supramolecular arrays can be produced from redundant ligand mixtures by molecular self-recognition and -selection, enabled by efficient error correction and cooperativity, and show an example of failed self-selection due to error tolerance in the ligand mixture, leading to a disordered structure.

Molecular Recognition between Glyconectins as an Adhesion Self-assembly Pathway to Multicellularity

The appearance of multicellular forms of life has been tightly coupled to the ability of an organism to retain its own anatomical integrity and to distinguish self from non-self. Large glycoconjugates, which make up the outermost cell surface layer of all Metazoans, are the primary candidates for the primordial adhesion and recognition functions in biological self-assembly systems. Atomic force microscopy experiments demonstrated that the binding strength between a single pair of Porifera cell surface glyconectin 1 glycoconjugates from Microciona prolifera can hold the weight of 1600 cells, proving their adhesion functions. Here, measurement of molecular self-recognition of glyconectins (GNs) purified from three Porifera species was used as an experimental model for primordial xenogeneic self/non-self discrimination. Physicochemical and biochemical characterization of the three glyconectins, their glycans, and peptides using gel electrophoresis, ultracentrifugation, NMR, mass spectrometry, glycosaminoglycan-degrading enzyme treatment, amino acid and carbohydrate analyses, and peptide mapping showed that GNs define a new family of proteoglycan-like molecules exhibiting species-specific structures with complex and repetitive acidic carbohydrate motives different from the classical proteoglycans and mucins. In functional self-assembly color-coded bead, cell, and blotting assays, glyconectins displayed species-specific recognition and adhesion. Affinity-purified monospecific polyclonal antibodies prepared against GN1, -2, and -3 glycans selectively inhibited cell adhesion of the respective sponge species. These results together with species-specific coaggregation of GN carbohydrate-coated beads with cells showed that GN glycans are functional in cell recognition and adhesion. The specificity of carbohydrate-mediated homophilic GN interactions in Porifera approaches the binding selectivity of the evolutionarily advanced immunoglobulin superfamily. Xenoselectivity of primordial glyconectin to glyconectin recognition may be a new paradigm in the self-assembly and non-self discrimination pathway of cellular adhesion leading to multicellularity.

Ligand design and self-recognition: a copper(II) complex that dimerizes via hydrogen bonds

The ligand ethylene-dianthranilate ( 1) can accommodate both tetrahedral and square-planar coordination geometries. When bound to Cu(II) and in the presence of an exogenous axial ligand, 1 adopts an equatorial binding mode. This coordination enforces a parallel geometry of the NH bonds and, by molecular self-recognition, predisposes the complex to dimerization by forming back-to-back hydrogen bonding interactions.

Chiral monomeric and homochiral dimeric copper(II) complexes of a new chiral ligand, N-(1,2-bis(2-pyridyl)ethyl)pyridine-2-carboxamide: an example of molecular self-recognition.

Reaction of Cu(ClO(4))(2) x 6H(2)O with a racemic mixture of the novel chiral ligand N-(1,2-bis(2-pyridyl)ethyl)pyridine-2-carboxamide (PEAH) affords only the homochiral dimeric copper(II) complexes [Cu(2)((R)()PEA)(2)](ClO(4))(2) and [Cu(2)((S)()PEA)(2)](ClO(4))(2) in a 1:1 ratio. The phenomenon of molecular self-recognition is also observed when a racemic mixture of the monomeric copper(II) complex [Cu((R(S))()PEA)(Cl)(H(2)O)] is converted into the homochiral dimeric species [Cu(2)((R(S))()PEA)(2)](ClO(4))(2) via reaction with Ag(+) ion. This is the first report of direct conversion of a racemic mixture of a chiral monomeric copper(II) complex to a mixture of the homochiral dimers.

Nanoconstruction of Microspheres and Microcapsules Using Proton-Induced Phase Transitions: Molecular Self-Recognition by Diamide Diacids in Water

Bis(N α -amido-L-phenylalanine)-1,1-cyclobutane dicarboxylate (5) was studied by Fourier transform infrared (FTIR) spectroscopy, variable-temperature NMR (VT-NMR), transmission electron microscopy, X-ray crystallography, Raman microscopy, and a novel imaging technique known as soft X-ray microscopy (XRM). Diamide diacid 5 was shown to self-associate into solid microspheres during a proton-induced phase transition from the solvated state to the desolvated assembled state. These diverse techniques allowed for the delineation of the molecular recognition events involved in the assembly process. X-ray crystallography revealed that 5 packs in a bundled helical array comprised of two types of intermolecular hydrogen bonds (i.e., OC=O…HN and COOH…O=CN). VT-NMR and IR measurements of 5 (1 mM in CDCl 3 ) revealed the small temperature dependence of the amide NH chemical shift (Δδ/ΔT = -1.1 ppb/K) and the availability of the free amide NH of 5 to form intermolecular hydrogen bonds. Supramolecular rodlike structures were observed during the aqueous assembly of 5 into microspheres by XRM. Raman microscopy confirmed that nearly identical bonding patterns are present in the assembled microsphere and the crystal architecture of 5. Collectively, these observations provide compelling evidence that the assembly of 5 occurs via crystalline supramolecular intermediates, which are similar in shape and have complementary bonding motifs for proper self-recognition. Competition experiments involving varying concentrations of 5 and its microcapsule-forming cyclopropane analogue 3 revealed that molecular fidelity was less important to the microsphere-forming process than the related capsule-forming process.

Molecular self-recognition and adhesion via proteoglycan to proteoglycan interactions as a pathway to multicellularity: atomic force microscopy and color coded bead measurements in sponges.

During the emergence of multicellular organisms, molecular mechanisms evolved to allow maintenance of anatomical integrity and self-recognition. We propose that carbohydrates from proteoglycans, as the most peripheral cell surface, and matrix molecules might have provided these key adhesion and recognition functions. If so, the Porifera as the simplest metazoans alive today should retain, at least in part, proteoglycan adhesion and recognition mechanisms. Early work on cell adhesion of dissociated marine sponge cells provided important phenomenological evidence for cell sorting. Here is reviewed recent work on molecular mechanisms of cell recognition and adhesion mediated by cell surface proteoglycans purified from three marine sponge species, Microciona prolifera, Halichondria panicea, and Cliona celata. Biochemical characterization of isolated proteoglycans showed that each species expressed a unique type of primordial molecule named glyconectins. These proteoglycans displayed species-specific self-recognition and adhesion in color-coded bead, cell, and blotting assays. The specificity of homophilic proteoglycan to proteoglycan interactions in the Porifera approaches the binding selectivity of the evolutionarily advanced immunoglobulin superfamily system. Such xeno-selectivity may be a new paradigm for the molecular self-recognition, which was a fundamental requirement in the self/non-self discrimination during the emergence of multicellularity and further divergence of species. We have used atomic force microscopy (AFM) technology to directly measure intermolecular binding strength between individual pairs of ligand and receptor molecules in physiological solution. Homophilic glyconectin interactions were investigated by AFM after covalent attachment of the protein core to the sensor tip and to a flat surface, leaving the carbohydrates unmodified. AFM measurements of the binding strength between glyconectins indicated that one pair of molecules could theoretically hold the weight of 1,600 cells in physiological solution. These results provided the first essential and quantitative evidence that proteoglycan-proteoglycan binding can perform the adhesion function that we have assigned to it. Our investigations with purified proteoglycans from the marine sponge M. prolifera (glyconectin 1) using bead and cell adhesion assays have provided evidence that a new molecular mechanism of polyvalent and specific glycan-glycan binding between proteoglycans can mediate cell recognition and adhesion. Partial sequencing of the glycans has revealed two new cell adhesion carbohydrate structures: (3)GlcNAc(3OSO3)beta1-3Fuc and Pyr4,6Galbeta1-4GlcNAcbeta1-3Fuc.

Study of the Interactions between Neurophysin II and Dipeptide Ligand by Means of Molecular Dynamics

The nonapeptide hormones oxytocin (OT) and vasopressin (VP), while transported in the posterior pituitary, are packaged into neurosecretory granules (NSG) in the form of high associates with disulfide-rich proteins known as neurophysin I (NPI) and neurophysin II (NPII), respectively. In the NSG, neurophysins serve as carrier proteins to the hormones, until the latter are dissociated upon secretion into blood. To shed more light on molecular self-recognition between NPs, and between NPs and their ligands, we have studied their molecular association, using as a starting point the recently published solid-state structure (Cα-trace) of the neurophysin II-dipeptide complex.

Crystal construction and molecular recognition for [Cr(CO)6

The molecular organization in crystals of the prototypical organometallic molecule [Cr(CO)6] has been investigated by means of packing-potential-energy calculations and computer graphics analysis. The atom–atom pairwise-potential-energy method has been used to study the interaction energy between molecular pairs and the molecular self-recognition process which leads to crystal construction. Alternative crystal structures have been generated and compared with the experimentally observed structure in terms of packing cohesion.

Molecular self-recognition and crystal building in transition-metal carbonyl clusters: the cases of ruthenium and iron carbonyls (Ru3(CO)12 and Fe3(CO)12)

Molecular self-recognition and crystal building in transition-metal carbonyl clusters: the cases of ruthenium and iron carbonyls (Ru3(CO)12 and Fe3(CO)12)