Dual-peptide functionalized nanoparticles for therapeutic use

Peptide-functionalized nanoparticles combine the best of both; the ability of nanoparticles to deliver a drug “cargo” throughout the body and the ability of peptides to selectively target certain cell types or biological systems. The vast majority of peptide-functionalized nanoparticles employ only one type of peptide, however, to truly realize the potential of these systems in medicine, nanoparticles equipped with two or even more peptide functionalities are desirable. In this review, the latest developments in dual-peptide functionalized nanoparticles are discussed. These are categorized depending on their structure; first broadly into grafted and self-assembled dual-peptide-nanoparticles with the former then subdivided further into nonconjugated, linearly conjugated and branched conjugated dual-peptide functionalized nanoparticles. These different categories of dual-peptide nanoparticles are then discussed with regards to the type of functional peptides used and their role in selective targeting nanomedicine

Energy Transfer to Ni-Amine Complexes in Dual Catalytic, Light-Driven C-N Cross-Coupling Reactions

Dual catalytic light-driven cross-coupling methodologies utilizing a Ni(II) salt with a photocatalyst (PC) have emerged as promising methodologies to forge aryl C-N bonds under mild conditions. The recent discovery that the PC can be omitted and the Ni(II) complex directly photoexcited suggests that the PC may perform energy transfer (EnT) to the Ni(II) complex, a mechanistic possibility that has recently been proposed in other systems across dual Ni photocatalysis. Here, we report the first studies in this field capable of distinguishing EnT from electron transfer (ET), and the results are consistent with Förster-type EnT from the excited state [Ru(bpy)3]Cl2 PC to Ni-amine complexes. The structure and speciation of Ni-amine complexes that are the proposed EnT acceptors were elucidated by crystallography and spectroscopic binding studies. With the acceptors known, quantitative Förster theory was utilized to predict the ratio of quenching rate constants upon changing the PC, enabling selection of an organic phenoxazine PC that proved to be more effective in catalyzing C-N cross-coupling reactions with a diverse selection of amines and aryl halides

Double tailed scorpiand-type calix[10]phyrin: Synthesis and proton-driven anion recognition features

Reported here is a large oligopyrrole macrocycle, a calix[10]phyrin bearing two diformyl substituents. The combination of conjugation provided by two pentapyrrolic subunits and flexibility resulting from the presence of sp3 hybridized meso bridges allows the system to adopt a double tailed, scorpiand-like structure with two near-symmetric binding pockets. In methanol solution, this macrocycle was found to interact with a number of test acids, including sulfuric acid, trifluoroacetic acid, phosphoric acid, hydrochloric acid, and fluoroboric acid, via a combination of protonation and counter anion binding. Species specific behavior was seen, allowing for the colorimetric-based discrimination between the acids. Efforts to model the underlying binding equilibria led to the conclusion that upon treatment with excess H2SO4, up to four protons and two counteranions are bound, whereas in the case of HCl the dominant species is a monoanionic complex. The responses of several other acids were rationalized in terms of these limiting scenarios

Rootless tephra stratigraphy and emplacement processes

Volcanic rootless cones are the products of thermohydraulic explosions involving rapid heat transfer from active lava (fuel) to external sources of water (coolant). Rootless eruptions are attributed to molten fuel–coolant interactions (MFCIs), but previous studies have not performed systematic investigations of rootless tephrostratigraphy and grain-size distributions to establish a baseline for evaluating relationships between environmental factors, MFCI efficiency, fragmentation, and patterns of tephra dispersal. This study examines a 13.55-m-thick vertical section through an archetypal rootless tephra sequence, which includes a rhythmic succession of 28 bed pairs. Each bed pair is interpreted to be the result of a discrete explosion cycle, with fine-grained basal material emplaced dominantly as tephra fall during an energetic opening phase, followed by the deposition of coarser-grained material mainly as ballistic ejecta during a weaker coda phase. Nine additional layers are interleaved throughout the stratigraphy and are interpreted to be dilute pyroclastic density current (PDC) deposits. Overall, the stratigraphy divides into four units: unit 1 contains the largest number of sediment-rich PDC deposits, units 2 and 3 are dominated by a rhythmic succession of bed pairs, and unit 4 includes welded layers. This pattern is consistent with a general decrease in MFCI efficiency due to the depletion of locally available coolant (i.e., groundwater or wet sediments). Changing conduit/vent geometries, mixing conditions, coolant and melt temperatures, and/or coolant impurities may also have affected MFCI efficiency, but the rhythmic nature of the bed pairs implies a periodic explosion process, which can be explained by temporary increases in the water-to-lava mass ratio during cycles of groundwater recharge.We acknowledge financial support from the National Science Foundation (NSF) grant EAR-119648, National Aeronautics and Space Administration (NASA) Mars Data Analysis Program (MDAP) grant NNG05GQ39G, NASA Mars Fundamental Research Program (MFRP) grant NNG05GM08G, NASA Postdoctoral Program (NPP), Geological Society of America (GSA), and Icelandic Centre for Research (RANNÍS). We are grateful to Stephen Scheidt for his help developing photogrammetric reconstructions of Cone 53 and we thank Richard Brown for his editorial handing of this manuscript as well as Peter Reynolds and Adrian Pittari for their constructive reviews.Peer Reviewe

Competing Energy Transfer Pathways in a Five-Chromophore Perylene Array

A perylene (donor-dimer)-acceptor-(donor-dimer) pentamer array is synthesized to investigate the competition between excimer formation and Förster resonance energy transfer. Using time-resolved fluorescence, we show that, upon excitation, the isolated perylene dimer forms an excimer with a time constant of 4.3 ns. However, in the pentamer array, when either of two constituent dimers donate their energy to the acceptor fluorophore, the excimer energy trap is eliminated. The pentamer macromolecule shows broad absorption and reduced self-absorption, at some cost to fluorescence quantum yield

Molecular dissection of the soluble photosynthetic antenna from the cryptophyte alga Hemiselmis andersenii

Cryptophyte algae have a unique phycobiliprotein light-harvesting antenna that fills a spectral gap in chlorophyll absorption from photosystems. However, it is unclear how the antenna transfers energy efficiently to these photosystems. We show that the cryptophyte Hemiselmis andersenii expresses an energetically complex antenna comprising three distinct spectrotypes of phycobiliprotein, each composed of two αβ protomers but with different quaternary structures arising from a diverse α subunit family. We report crystal structures of the major phycobiliprotein from each spectrotype. Two-thirds of the antenna consists of open quaternary form phycobiliproteins acting as primary photon acceptors. These are supplemented by a newly discovered open-braced form (~15%), where an insertion in the α subunit produces ~10 nm absorbance red-shift. The final components (~15%) are closed forms with a long wavelength spectral feature due to substitution of a single chromophore. This chromophore is present on only one β subunit where asymmetry is dictated by the corresponding α subunit. This chromophore creates spectral overlap with chlorophyll, thus bridging the energetic gap between the phycobiliprotein antenna and the photosystems. We propose that the macromolecular organization of the cryptophyte antenna consists of bulk open and open-braced forms that transfer excitations to photosystems via this bridging closed form phycobiliprotein

Hydrogels with intrinsic antibacterial activity prepared from naphthyl anthranilamide (NaA) capped peptide mimics

In this study, we prepared antibacterial hydrogels through the self-assembly of naphthyl anthranilamide (NaA) capped amino acid based cationic peptide mimics. These ultra-short cationic peptide mimics were rationally designed with NaA as a capping group, l-phenylalanine, a short aliphatic linker, and a cationic group. The synthesized peptide mimics efficiently formed hydrogels with minimum gel concentrations between 0.1 and 0.3%w/v. The resulting hydrogels exhibited desirable viscoelastic properties which can be tuned by varying the cationic group, electronegative substituent, or counter anion. Importantly, nanofibers from the NaA-capped cationic hydrogels were found to be the source of hydrogels’ potent bacteriacidal actvity against both Gram-positive and Gram-negative bacteria while remaining non-cytotoxic. These intrinsically antibacterial hydrogels are ideal candidates for further development in applications where bacterial contamination is problematic

Landscape evolution associated with the 2014–2015 Holuhraun eruption in Iceland

The 2014–2015 Holuhraun eruption in Iceland developed between the outlet glacier Dyngjujökull and the Askja central volcano and extruded a bulk lava volume of over 1 km3 onto the floodplain of the Jökulsá á Fjöllum river, making it the largest effusive eruption in Iceland during the past 230 years. Time-series monitoring using a combination of traditional aerial imaging, unmanned aerial systems, and field-based geodetic surveys, established an unprecedented record of the hydrological response of the river system to this lava flow. We observed: (1) the formation of lava-dammed lakes and channels produced during dam-breaching events; (2) percolation of glacial meltwater into the porous and permeable lava, forming an ephemeral hydrothermal system that included hot pools and hot springs that emerged from the lava flow front; and (3) the formation of new seepage channels caused by upwelling of water around the periphery of the lava flow. The observations show that lava flows, like the one produced by the 2014–2015 Holuhraun eruption, can cause significant hydrological changes that continue for several years after the lava is emplaced. Documenting these processes is therefore crucial for our interpretation of volcanic landscapes and processes of lava–water interaction on both Earth and Mars

Halide Noninnocence and Direct Photoreduction of Ni(II) Enables Coupling of Aryl Chlorides in Dual Catalytic, Carbon-Heteroatom Bond-Forming Reactions

Recent mechanistic studies of dual photoredox/Ni-catalyzed, light-driven cross-coupling reactions have found that the photocatalyst (PC) operates through either reductive quenching or energy transfer cycles. To date, reports invoking oxidative quenching cycles are comparatively rare and direct observation of such a quenching event has not been reported. However, when PCs with highly reducing excited states are used (e.g., Ir(ppy)3), photoreduction of Ni(II) to Ni(I) is thermodynamically feasible. Recently, a unified reaction system using Ir(ppy)3was developed for forming C-O, C-N, and C-S bonds under the same conditions, a prospect that is challenging with PCs that can photooxidize these nucleophiles. Herein, in a detailed mechanistic study of this system, we observe oxidative quenching of the PC (Ir(ppy)3or a phenoxazine) via nanosecond transient absorption spectroscopy. Speciation studies support that a mixture of Ni-bipyridine complexes forms under the reaction conditions, and the rate constant for photoreduction increases when more than one ligand is bound. Oxidative addition of an aryl iodide was observed indirectly via oxidation of the resulting iodide by Ir(IV)(ppy)3. Intriguingly, the persistence of the Ir(IV)/Ni(I) ion pair formed in the oxidative quenching step was found to be necessary to simulate the observed kinetics. Both bromide and iodide anions were found to reduce the oxidized form of the PC back to its neutral state. These mechanistic insights inspired the addition of a chloride salt additive, which was found to alter Ni speciation, leading to a 36-fold increase in the initial turnover frequency, enabling the coupling of aryl chlorides