Duplex molecular strands based on the 3,6-diaminopyridazine hydrogen bonding motif: amplifying small-molecule self-assembly preferences through preorganization and iterative arrangement of binding residues

Structural parameters obtained through single-crystal X-ray diffraction analysis of the one-dimensional H-bonding motif expressed by 3,6-diaminopyridazine are applied to the design of related monomeric, dimeric, and trimeric duplex molecular strands. The mode of assembly and the interstrand affinity of the oligomers are established in solution by (1)H NMR dilution experiments, isothermal titration calorimetry (ITC), and vapor pressure osmometry. Single-crystal X-ray crystallographic analysis of the dimeric diaminopyridazine 2a corroborates the intended duplex mode of assembly. Binding free energy per unimer (-DeltaG degrees /n) increases upon extension from monomer to dimer to trimer, signifying a positive cooperative effect. Micromolar binding affinity (K(d) = 1.25 +/- 0.1 microM) was determined for the duplex trimer by ITC in 1,2-dichloroethane at 20 degrees C. These data provide further insight into the structural and interactional features of synthetic duplex oligomers required for high-affinity, high-specificity binding and define new recognition elements for use in nanoscale assembly.     

Hydrogen bonding-mediated self-assembly of anthranilamide-based homodimers through preorganization of the amido and ureido binding sites

The self-assembly of a novel series of hydrogen bonding-mediated homodimers in chloroform-d has been described. Six anthranilamide-based monomers have been prepared, in which two self-binding formamido, trifluoroacetamido, acetamido, butyl or methyl ureido units are introduced at the two ends of the backbones. Quantitative ¹H NMR investigations in chloroform-d revealed that the formamido and ureido units are more efficient than acetamido to induce the formation of stable homodimers. The association constants of all the new homodimers have been determined by ¹H NMR dilution method. Multiply hydrogen bonding-driven binding patterns have been proposed for the homodimers. It is also found that ureido-derived homodimers do not adopt common linear binding pattern observed for simple urea derivatives.     

Effect of conformational preorganization of a three-armed host on anion binding and selectivity

A set of three-armed urea-containing anion receptors was prepared. The receptors all have the same binding topology but differ in the level of conformational preorganization with respect to the arrangement of the side-arms relative to the platform and within the side arms themselves. This is mirrored in a specific increase (x 2.5) in the binding constant for chloride and in a 12-fold increase in the chloride/nitrate-selectivity.     

Neighboring pyrrolidine amide participation in thioether oxidation. Methionine as a "hopping" site

Methionine residues have been shown to function as efficient "hopping" sites in long-range electron transfer in model polyprolyl peptides. We suggest that a key to this ability of methionine is stabilization of the transient sulfur radical cation by neighboring proline amide participation. That is, in a model system a neighboring pyrrolidine amide lowers the oxidation potential of the thioether by over 0.5 V by formation of a two-center three-electron SO bond.     

Thixotropic organogels based on a simple N-hydroxyalkyl amide: rheological and aging properties

The thixotropic properties ofthermoreversible organogels composed ofN-3-hydroxypropyl dodecanamide and various apolar fluids have been investigated by X-ray scattering, light microscopy, and rheo-optics experiments. This revealed that gel formation occurs via a precipitation process. Depending upon the cooling rate, large interconnected aggregates are formed and induce an elastic behavior. When submitted to a shear flow, these aggregates disentangled and became aligned in the direction of the velocity. Nevertheless, shear does not alter the structure of the individual aggregate and connections between the aggregates are quickly rebuilt due to gravity and thermal fluctuations when the applied flow is stopped. The alignment under flow and the reformation of the connections after the cessation of the shear induces the thixotropic behavior.     

Equivalence of two approaches for modeling ion permeation through a transmembrane channel with an internal binding site

Ion permeation through transmembrane channels has traditionally been modeled using two different approaches. In one approach, the translocation of the permeant ion through the channel pore is modeled as continuous diffusion and the rate of ion transport is obtained from solving the steady-state diffusion equation. In the other approach, the translocation of the permeant ion through the pore is modeled as hopping along a discrete set of internal binding sites and the rate of ion transport is obtained from solving a set of steady-state rate equations. In a recent work [Zhou, J. Phys. Chem. Lett. 1, 1973 (2010)], the rate constants for binding to an internal site were further calculated by modeling binding as diffusion-influenced reactions. That work provided the foundation for bridging the two approaches. Here we show that, by representing a binding site as an energy well, the two approaches indeed give the same result for the rate of ion transport.     

Synthesis and characterization of a tripodal amide ligand and its binding with anions of different dimensionality

Synthesis and crystal structure of a tren-based amide, L(1), N,N',N'-tris[(2-amino-ethyl)-3-nitro-benzamide] is reported. The crystallographic results show intramolecular hydrogen bonding and aromatic pi...pi stacking among tripodal arms which prevent opening of the receptor cavity. Intermolecular hydrogen bonding in L1 generates the sheetlike network in the solid state. The structural aspects of binding halides (1 and 2), nitrate (3), perchlorate (4), and hexafluorosilicate (5) with the protonated L1 are examined crystallographically. Protonation at the apical nitrogen of L1 in the presence of anions shows a structural transformation from sheet to bilayer network. Anion binding with multiple receptor units is observed via amide N-H...anion and aryl C-H...anion hydrogen-bonding interactions in all the complexes. The aryl group having nitro functionality that contributes to anion binding in complexes 1-5 through CH...anion interactions (either para or meta to nitro C-H) is noteworthy. These studies also show higher anion coordination of chloride (8) and hexafluorosilicate (14) with L1H+.     

Solution stability and variability in a simple model of globular proteins

It is well known among molecular biologists that proteins with a common ancestor and that perform the same function in similar organisms, can have rather different amino-acid sequences. Mutations have altered the amino-acid sequences without affecting the function. A simple model of a protein in which the interactions are encoded by sequences of bits is introduced, and used to study how mutations can change these bits, and hence the interactions, while maintaining the stability of the protein solution. This stability is a simple minimal requirement on our model proteins which mimics part of the requirement on a real protein to be functional. The properties of our model protein, such as its second virial coefficient, are found to vary significantly from one model protein to another. It is suggested that this may also be the case for real proteins in vivo.     

RNA binding and thiolytic stability of a quinoline-containing helix-threading peptide

Helix-threading peptides (HTPs) bind selectively to sites predisposed to intercalation in folded RNA molecules placing peptide functional groups into the dissimilar grooves of the duplex. Here we report the design and synthesis of new HTPs with quinoline as the intercalation domain. A quinoline-containing HTP is shown to bind selectively to duplex RNA binding sites. Furthermore, the affinity cleavage pattern generated using an EDTA.Fe modified derivative is consistent with minor groove localization of its N-terminus. This compound binds base-pair steps flanked by single nucleotide bulges on the 3' side on both strands, whereas bulges on the 5' side of the intercalation site do not support binding. Furthermore, unlike acridine HTPs, the quinoline compound is resistant to thiolytic degradation that leads to loss of RNA-binding activity. The RNA-binding selectivity and stability observed for quinoline-containing HTPs make them excellent candidates for further development as regulators of intracellular RNA function.     

Multidimensional stability analysis of a family of biparametric iterative methods: CMMSE2016

In this paper, we present a multidimensional real dynamical study of the Ostrowsky–Chun family of iterative methods to solve systems of nonlinear equations. This family was defined initially for solving scalar equations but, in general, scalar methods can be transferred to make them suitable to solve nonlinear systems. The complex dynamical behavior of the rational operator associated to a scalar method applied to low-degree polynomials has shown to be an efficient tool for analyzing the stability and reliability of the methods. However, a good scalar dynamical behavior does not guarantee a good one in multidimensional case. We found different real intervals where both parameters can be defined assuring a completely stable performance and also other regions where it is dangerous to select any of the parameters, as undesirable behavior as attracting elements that are not solution of the problem to be solved appear. This performance is checked on a problem of chemical wave propagation, Fisher’s equation, where the difference in numerical results provided by those elements of the class with good stability properties and those showed to be unstable, is clear.     

Increasing the stability of an enzyme toward hostile organic solvents by directed evolution based on iterative saturation mutagenesis using the B-FIT method

Mutants of the lipase from Bacillus subtilis, previously engineered for enhanced thermostability using directed evolution based on the B-FIT method, show significantly increased tolerance to hostile organic solvents.     

2-amidopyrroles and 2,5-diamidopyrroles as simple anion binding agents.

Four new 2-amidopyrroles and 2,5-diamidopyrroles have been synthesized and their anion complexation properties investigated. The crystal structures of these receptors have been elucidated and reveal hydrogen bonding in the solid state leading to dimer and network formation. Selectivity for oxo-anions has been demonstrated by (1)H NMR titration techniques.     

Determination of binding site concentration and average binding constant by the method of equilibrium sorption: Evidence for lysine as a principal receptor site for collagen-enzyme binding

The contribution of lysyl ϵ-amino groups to the noncovalent binding on enzymes to collagen has been determined by the method of equilibrium sorption. The sorption or binding of enzyme by chemically modified, and by the corresponding unmodified membraneous collagen, was determined as a function of enzyme concentration. Chemical modification of lysyl ϵ-amino groups was accomplished by carbamylation of the collagen membrane with potassium cyanate. The collagen membranes were contacted with a purified β-galactosidase (E. coli K₁₂). The enzyme was purified by affinity chromato- graphy. Analysis of the resultant sorption isotherms allowed determination of the heterogeneity index (a) and the concentration of active binding sites (A_o). Binding constants (K_o) and the free energy of binding (δG) were also computed from the sorption data.The results of these studies have shown that lysyl ϵ-amino groups of collagen are primary receptor sites for enzyme binding (β-galactosidase, E. coli K₁₂) and that carbamylation of the collagen membrane resulted in a decrease in active binding sites with little or no change in the binding constant of the remaining sites.     

DNA-modified electrodes. Part 6. A new method for the determination of binding constants and binding site sizes

A new method was developed to obtain the binding constant (K) and binding site size (n) for the interaction of DNA with other molecules using DNA-modified gold electrodes. This method is simple and microsample-consuming compared with conventional solution methods. A Q-basic program was designed to calculate K and n values. The results show that the K and n values obtained by the new method approach those obtained by conventional electrochemical methods, indicating the suitability of this method.     

DNA-modified electrodes. Part 6. A new method for the determination of binding constants and binding site sizes

A new method was developed to obtain the binding constant (K) and binding site size (n) for the interaction of DNA with other molecules using DNA-modified gold electrodes. This method is simple and microsample-consuming compared with conventional solution methods. A Q-basic program was designed to calculate K and n values. The results show that the K and n values obtained by the new method approach those obtained by conventional electrochemical methods, indicating the suitability of this method. Received: 22 July 1998 / Revised: 24 November 1998 / Accepted: 27 November 1998     

Simultaneous anion and cation binding by a simple polymer-bound ureidopyridyl ligand

A polymer-supported ligand capable of simultaneous anion and cation binding is reported along with X-ray crystallographic data showing potential binding modes.     

Three-component electrosynthesis of spirooxindole-pyran derivatives through a simple and efficient method

An eco-friendly and highly efficient process has been applied to synthesize spirooxindole-pyran derivatives in a one-pot container via a three-component reaction of isatins, malononitrile, and an enolizable C H-activated compound of diethyl 3-oxopentanedioate under constant current in n-propanol under a temperature of 50°C. The proposed method shows high yields through green reaction conditions along with other significant advantages. Among which stand out applying clean electrons as a reproducible source of energy instead of an organic catalyst, using an environmentally friendly solvent for instance propanol, a multicomponent reaction with mild condition happening in a one-pot container, and no chromatographic separation.