Annulation of Tetrathiafulvalene to the Bay Region of Perylenediimide: Fast Electron-Transfer Processes in Polar and Nonpolar Solvents

A tetrathiafulvalene donor has been annulated to the bay region of perylenediimide through a 1H-benzo-[d]pyrrolo[1,2-a]imidazol-1-one spacer affording an extended pi-conjugated molecular dyad (TTF-PDI). To gain insight into its ground- and excited-state electronic properties, the reference compound Ph-PDI has been prepared via a direct Schiff-base condensation of N,N'-bis(1-octylnonyl) benzoperylene-1',2':3,4:9,10-hexacarboxylic-1',2'-anhydride-3,4:9,10-bis (imide) with benzene-1,2-diamine. Both the experimental and the computational (DFT) results indicate that TTF-PDI exhibits significant intramolecular electronic interactions giving rise to an efficient photoinduced charge-separation process. Free-energy calculations verify that the process from TTF to the singlet-excited state of PDI is exothermic in both polar and nonpolar solvents. Fast adiabatic electron-transfer processes of a compactly fused, pi-conjugated TTF-PDI dyad in benzonitrile, 2-methyltetrahydrofuran, anisole and toluene were observed by femtosecond transient absorption spectral measurements. The lifetimes of radical-ion pairs slightly increase with decreasing the solvent polarities, suggesting that the charge-recombination occurs in the Marcus inverted region. By utilizing the nanosecond transient absorption technique, the intermolecular electron-transfer process in a mixture of has been observed via the triplet excited PDI for the first time.

A triplet spike-timing–dependent plasticity model generalizes the Bienenstock–Cooper–Munro rule to higher-order spatiotemporal correlations

Synaptic strength depresses for low and potentiates for high activation of the postsynaptic neuron. This feature is a key property of the Bienenstock–Cooper–Munro (BCM) synaptic learning rule, which has been shown to maximize the selectivity of the postsynaptic neuron, and thereby offers a possible explanation for experience-dependent cortical plasticity such as orientation selectivity. However, the BCM framework is rate-based and a significant amount of recent work has shown that synaptic plasticity also depends on the precise timing of presynaptic and postsynaptic spikes. Here we consider a triplet model of spike-timing–dependent plasticity (STDP) that depends on the interactions of three precisely timed spikes. Triplet STDP has been shown to describe plasticity experiments that the classical STDP rule, based on pairs of spikes, has failed to capture. In the case of rate-based patterns, we show a tight correspondence between the triplet STDP rule and the BCM rule. We analytically demonstrate the selectivity property of the triplet STDP rule for orthogonal inputs and perform numerical simulations for nonorthogonal inputs. Moreover, in contrast to BCM, we show that triplet STDP can also induce selectivity for input patterns consisting of higher-order spatiotemporal correlations, which exist in natural stimuli and have been measured in the brain. We show that this sensitivity to higher-order correlations can be used to develop direction and speed selectivity.

Excited state properties of formamide in water solution: An ab initio study

We present ab initio quantum calculation of the optical properties of formamide in vapor phase and in water solution. We employ time dependent density functional theory for the isolated molecule and many-body perturbation theory methods for the system in solution. An average over several molecular dynamics snapshots is performed to take into account the disorder of the liquid. We find that the excited stateproperties of the gas-phase formamide are strongly modified by the presence of the water solvent: the geometry of the molecule is distorted and the electronic and optical properties are severely modified. The important interaction among the formamide and the water molecules forces us to use fully quantum methods for the calculation of the excited stateproperties of this system. The excitonic wave function is localized both on the solute and on part of the solvent.

Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function

Background The Nef protein of HIV facilitates virus replication and disease progression in infected patients. This role as pathogenesis factor depends on several genetically separable Nef functions that are mediated by interactions of highly conserved protein-protein interaction motifs with different host cell proteins. By studying the functionality of a series of nef alleles from clinical isolates, we identified a dysfunctional HIV group O Nef in which a highly conserved valine-glycine-phenylalanine (VGF) region, which links a preceding acidic cluster with the following proline-rich motif into an amphipathic surface was deleted. In this study, we aimed to study the functional importance of this VGF region. Results The dysfunctional HIV group O8 nef allele was restored to the consensus sequence, and mutants of canonical (NL4.3, NA-7, SF2) and non-canonical (B2 and C1422) HIV-1 group M nef alleles were generated in which the amino acids of the VGF region were changed into alanines (VGF→AAA) and tested for their capacity to interfere with surface receptor trafficking, signal transduction and enhancement of viral replication and infectivity. We found the VGF motif, and each individual amino acid of this motif, to be critical for downregulation of MHC-I and CXCR4. Moreover, Nef’s association with the cellular p21-activated kinase 2 (PAK2), the resulting deregulation of cofilin and inhibition of host cell actin remodeling, and targeting of Lck kinase to the trans-golgi-network (TGN) were affected as well. Of particular interest, VGF integrity was essential for Nef-mediated enhancement of HIV virion infectivity and HIV replication in peripheral blood lymphocytes. For targeting of Lck kinase to the TGN and viral infectivity, especially the phenylalanine of the triplet was essential. At the molecular level, the VGF motif was required for the physical interaction of the adjacent proline-rich motif with Hck. Conclusion Based on these findings, we propose that this highly conserved three amino acid VGF motif together with the acidic cluster and the proline-rich motif form a previously unrecognized amphipathic surface on Nef. This surface appears to be essential for the majority of Nef functions and thus represents a prime target for the pharmacological inhibition of Nef.

In-frame triplet deletions in RHD alter the D antigen phenotype

BACKGROUND: The deletion of three adjacent nucleotides in an exon may cause the lack of a single amino acid, while the protein sequence remains otherwise unchanged. Only one such in-frame deletion is known in the two RH genes, represented by the RHCE allele ceBP expressing a "very weak e antigen." STUDY DESIGN AND METHODS: Blood donor samples were recognized because of discrepant results of D phenotyping. Six samples came from Switzerland and one from Northern Germany. The molecular structures were determined by genomic DNA nucleotide sequencing of RHD. RESULTS: Two different variant D antigens were explained by RHD alleles harboring one in-frame triplet deletion each. Both single-amino-acid deletions led to partial D phenotypes with weak D antigen expression. Because of their D category V-like phenotypes, the RHD(Arg229del) allele was dubbed DVL-1 and the RHD(Lys235del) allele DVL-2. These in-frame triplet deletions are located in GAGAA or GAAGA repeats of the RHD exon 5. CONCLUSION: Partial D may be caused by a single-amino-acid deletion in RhD. The altered RhD protein segments in DVL types are adjacent to the extracellular loop 4, which constitutes one of the most immunogenic parts of the D antigen. These RhD protein segments are also altered in all DV, which may explain the similarity in phenotype. At the nucleotide level, the triplet deletions may have resulted from replication slippage. A total of nine amino acid positions in an Rhesus protein may be affected by this mechanism.