Emergent Catalytic Behavior of Self‐Assembled Low Molecular Weight Peptide‐Based Aggregates and Hydrogels

We report a series of short peptides possessing the sequence (FE)_n or (EF)_n and bearing l ‐proline at their N‐terminus that self‐assemble into high aspect ratio aggregates and hydrogels. We show that these aggregates are able to catalyze the aldol reaction, whereas non‐aggregated analogues are catalytically inactive. We have undertaken an analysis of the results, considering the accessibility of catalytic sites, pK_a value shifts, and the presence of hydrophobic pockets. We conclude that the presence of hydrophobic regions is indeed relevant for substrate solubilization, but that the active site accessibility is the key factor for the observed differences in reaction rates. The results presented here provide an example of the emergence of a new chemical property caused by self‐assembly, and support the relevant role played by self‐assembled peptides in prebiotic scenarios. In this sense, the reported systems can be seen as primitive aldolase I mimics, and have been successfully tested for the synthesis of simple carbohydrate precursors.     

Bidentate ligation of heme analogues; novel biomimetics of peroxidase active site

The multifunctional nature of proteins that have iron-heme cofactors with noncovalent histidine linkage to the protein is controlled by the heme environment. Previous studies of these active-site structures show that the primary difference is the length of the iron-proximal histidine bond, which can be controlled by the degree of H-bonding to this histidine. Great efforts to mimic these functions with synthetic analogues have been made for more than two decades. The peroxidase models resulted in several catalytic systems capable of a large range of oxidative transformations. Most of these model systems modified the porphyrin ring covalently by directly binding auxiliary elements that control and facilitate reactivity; for example, electron-donating or -withdrawing substituents. A biomimetic approach to enzyme mimicking would have taken a different route, by attempting to keep the porphyrin ring system unaltered, as close as possible to its native form, and introducing all modifications at or close to the axial coordination sites. Such a model system would be less demanding synthetically, would make it easy to study the effect of a single structural modification, and might even provide a way to probe effects resulting from porphyrin exchange. We introduce here an alternative model system based on these principles. It consists of a two component system: a bis-imidazolyl ligand and an iron-porphyrin (readily substituted by a hemin). All modifications were introduced only to the ligand that engulfs the porphyrin and binds to the iron's fifth and sixth coordination sites. We describe the design, synthesis, and characterization of nine different model compounds with increased complexity. The primary tool for characterizing the environment of each complex Fe(III) center was the Extended X-ray Absorption Fine Structure (EXAFS) measurements, supported by UV/Vis, IR, and NMR spectroscopy and by molecular modeling. Introduction of asymmetry, by attaching different imidazoles as head groups, led to the formation of two axial bonds of different length. Addition of H-bonds to one of the imidazoles in an advanced model increased this differentiation and expanded the porphyrin ring. These complexes were found to be almost identical in structure to peroxidase active sites. Similarly to the peroxidases and other synthetic models, these compounds stabilize the green, compound I-like intermediate, and catalyze the oxidation of organic substrates.     

Controlling Field‐Effect Transistor Biosensor Electrical Characteristics Using Immunosorbent Assay

A method to modulate the signal of field‐effect transistor biosensors using an immunosorbent assay is described. A model system is used to show that binding of a secondary antibody, to which highly charged gold colloids are attached, to an analyte on the device floating gate can be used to induce strong electrostatic effects, which affect the device threshold voltage and source‐drain current. This process may be used for signal amplification, with the secondary binding specificity allowing for improved signal to noise ratio, which is of great importance for early disease detection.     

Modulating charge transfer through cyclic D,L-alpha-peptide self-assembly

We describe a concise, solid support-based synthetic method for the preparation of cyclic d,l-alpha-peptides bearing 1,4,5,8-naphthalenetetracarboxylic acid diimide (NDI) side chains. Studies of the structural and photoluminescence properties of these molecules in solution show that the hydrogen bond-directed self-assembly of the cyclic d,l-alpha-peptide backbone promotes intermolecular NDI excimer formation. The efficiency of NDI charge transfer in the resulting supramolecular assemblies is shown to depend on the length of the linker between the NDI and the peptide backbone, the distal NDI substituent, and the number of NDIs incorporated in a given structure. The design rationale and synthetic strategies described here should provide a basic blueprint for a series of self-assembling cyclic d,l-alpha-peptide nanotubes with interesting optical and electronic properties.     

The optimal MR acquisition strategy for exponential decay constants estimation

Estimating the relaxation constant of an exponentially decaying signal from experimental MR data is fundamental in diffusion tensor imaging, fractional anisotropy mapping, measurements of transverse relaxation rates and contrast agent uptake. The precision of such measurements depends on the choice of acquisition parameters made at the design stage of the experiments. In this report, chi(2) fitting of multipoint data is used to demonstrate that the most efficient acquisition strategy is a two-point scheme. We also conjecture that the smallest coefficient of variation of the decay constant achievable in any N-point experiment is 3.6 times larger than that in the image intensity obtained by averaging N acquisitions with minimal exponential weighting.     

Effect of cyano group substitution on metathetical reactions. IV. Substituent effects on the rates of cyanomethyl radical reaction with haloalkanes

Gamma radiation-induced free radical chain reactions in liquid mixtures of BrCH₂CN, eyelohexane (RH), and haloalkanes (XCCl₃) were studied. The kinetics of hydrogen and chlorine atom abstraction from CHCl₃, CH₃CCl₃, CH₂ClCCl₃, CHCl₂CCl₃, CF₃CCl₃, C₂Cl₆, CCl₃CN, and CCl₄ by CH₂CN radicals were investigated by a competitive method. The reactions investigated were Rate constant ratios k₃/k₂, k₅/k₆, k₇/k₂, and k₃/k₇ were determined at 180°C. In the CCl₄? RH? BrCH₂CN system k₃/k₂ was determined in the temperature range of 100–180°C, yielding log k₂ k₃ = ?0.11 ± 0.2 ?(3.34 ± 0.39/θ): where θ = 2.3RT in kcal/mol. The value E₂? E₃ was combined with existing data on E₃ to yield E₂(CCl₄) = 17.57 kcal/mol. The reactivity trend of CH₂CN is compared with that of R radicals. It is shown that in spite of a difference of about four orders of magnitude in k_Cl values, the reactive cyclohexyl radical is somewhat more selective than CH₂CN. It is proposed that the relative reactivities log[k₂(XCCl₃)/k₂(CH₃CCl₃)] can be correlated in terms of a dual-parameter Taft equation which takes into account both resonance and inductive substituent effects.     

The accuracy of whole brain N-acetylaspartate quantification

A non-localizing pulse sequence to quantify the total amount of N-acetylaspartate (NAA) in the whole brain (WBNAA) was introduced recently [Magn. Reson. Med. 40, 684–689 (1998)]. However, it is known that regional magnetic field inhomogeneities, ΔB₀s, arising from susceptibility differences at tissue interfaces, shift and broaden local resonances to outside the integration window, leading to an underestimation of the true amount of NAA in the entire brain. To quantify the upper limit of this loss, the whole-head proton MR spectrum (¹H-MRS) of the water was integrated over the same frequency width as the NAA. The ratio of this area/total-water-line was 75 ± 5% in 5 volunteers. The procedure was repeated with the brain-only water peak, obtained by summing signals only from voxels within that organ from a three-dimensional chemical-shift-imaging (3D CSI) set. It indicated that <10% of the water signal loss occurred in the brain. Therefore, by analogy, WBNAA accounts for >90% of that metabolite.     

Replication NAND gate with light as input and output

Logic operations can highlight information transfer within complex molecular networks. We describe here the design of a peptide-based replication system that can be detected by following its fluorescence quenching. This process is used to negate the signal of light-activated replication, and thus to prepare the first replication NAND gate.