Chemical synthesis of the innate immune modulator – bacterial d-glycero-β-d-manno-heptose-1,7-bisphosphate (HBP)

The bacterial metabolite and potent innate immune modulator d-glycero-β-d-manno-heptose-1,7-bisphosphate (HBP) and its α-configured counterpart d-glycero-α-d-manno-heptose-1,7-bisphosphate were synthesized via stereoselective anomeric phosphorylation of the peracetylated d,d-heptose 7-dibenzylphosphate by exploiting different nucleophilicity of equatorial and axial lactols in the d-manno-series. We also report a novel approach for anomeric phosphorylation using modified Mitsunobu reaction conditions and provide the first full structural characterization of HBP. The first chemical synthesis of HBP offers access to an anomerically pure structurally defined probe for biological studies and to a lead compound operating as a powerful stimulator of intracellular signaling for possible therapeutic immunomodulation.     

A Framework for Comparative Evaluation of Dosimetric Methods to Triage a Large Population Following a Radiological Event

BACKGROUND: To prepare for a possible major radiation disaster involving large numbers of potentially exposed people, it is important to be able to rapidly and accurately triage people for treatment or not, factoring in the likely conditions and available resources. To date, planners have had to create guidelines for triage based on methods for estimating dose that are clinically available and which use evidence extrapolated from unrelated conditions. Current guidelines consequently focus on measuring clinical symptoms (e.g., time-to-vomiting), which may not be subject to the same verification of standard methods and validation processes required for governmental approval processes of new and modified procedures. Biodosimeters under development have not yet been formally approved for this use. Neither set of methods has been tested in settings involving large-scale populations at risk for exposure. OBJECTIVE: To propose a framework for comparative evaluation of methods for such triage and to evaluate biodosimetric methods that are currently recommended and new methods as they are developed. METHODS: We adapt the NIH model of scientific evaluations and sciences needed for effective translational research to apply to biodosimetry for triaging very large populations following a radiation event. We detail criteria for translating basic science about dosimetry into effective multi-stage triage of large populations and illustrate it by analyzing 3 current guidelines and 3 advanced methods for biodosimetry. CONCLUSIONS: This framework for evaluating dosimetry in large populations is a useful technique to compare the strengths and weaknesses of different dosimetry methods. It can help policy-makers and planners not only to compare the methods' strengths and weaknesses for their intended use but also to develop an integrated approach to maximize their effectiveness. It also reveals weaknesses in methods that would benefit from further research and evaluation.     

Quantum Dot-Antibody Conjugates for Immunofluorescence Studies of Biomolecules and Subcellular Structures

Journal of Fluorescence - Quantum dots, or nanoscale semiconductors, are one of the most important materials for various research and development purposes. Due to their advantageous...     

The system of self-consistent QSPR-models for refractive index of polymers

Structural Chemistry - Quantitative structure–property/activity relationships (QSPRs/QSARs) are a component of modern natural science. The system of self-consistent models is a specific...     

The catalytic efficiency of Fe-containing nanocomposites based on highly dispersed silica in the reaction of CO2 hydrogenation

Research on Chemical Intermediates - Oxide Ni(80)Fe(20)/SiO2, Co(93)Fe(7)/SiO2, and Ni(19)Co(77)Fe(4)/SiO2 nanocomposites (NCs) were prepared using highly dispersed silica. It was modified by...     

A structural remedy toward bright dipolar fluorophores in aqueous media

The donor–acceptor (D–A) type dipolar fluorophores, an important class of luminescent dyes with two-photon absorption behaviour, generally emit strongly in organic solvents but poorly in aqueous media. To understand and enhance the poor emission behaviour of dipolar dyes in aqueous media, we undertake a rational approach that includes a systematic structure variation of the donor, amino substituent of acedan, an important two-photon dye. We identify several factors that influence the emission behaviour of the dipolar dyes in aqueous media through computational and photophysical studies on new acedan derivatives. As a result, we can make acedan dyes emit bright fluorescence under one- and two-photon excitation in aqueous media by suppressing the liable factors for poor emission: 1,3-allylic strain, rotational freedom, and hydrogen bonding with water. We also validate that these findings can be generally extended to other dipolar fluorophores, as demonstrated for naphthalimide, coumarin and (4-nitro-2,1,3-benzoxadiazol-7-yl)amine (NBD) dyes. The new acedan and naphthalimide dyes thus allow us to obtain much brighter two-photon fluorescent images in cells and tissues than in their conventional forms. As an application of these findings, a thiol probe is synthesized based on a new naphthalimide dye, which shows greatly enhanced fluorescence from the widely used N,N-dimethyl analogue. The results disclosed here provide essential guidelines for the development of efficient dipolar dyes and fluorescence probes for studying biological systems, particularly by two-photon microscopy.     

The room-temperature superstructure of ZrP2O7 is orthorhombic: there are no unusual 180 degrees P-O-P bond angles

The structure of room-temperature ZrP2O7 is shown to be orthorhombic by a combination of high-resolution synchrotron powder diffraction and single-crystal synchrotron diffraction data. Small nontwinned single crystals were obtained by synthesizing the compound using solvothermal methods at temperatures below the cubic to orthorhombic phase transition. The average P-O-P angle is 146 degrees. DFT calculations (B3LYP/AUG-cc-pVDZ) on the isolated P2O7(4-) anion yield a P-O-P angle of 153.42 degrees and indicate that the barrier to inversion is of the order 3.6 kJ mol(-1).     

Origin of the dynamic transition upon pressurization of crystalline proteins

We study the role of hydration water in the dynamic transition of low-hydrated proteins upon pressurization found recently (Meinhold, L.; Smith, J. C. Phys. Rev. E 2005, 72, 061908). Clustering and percolation of water in the hydration shells of protein molecules in crystalline Staphylococcal nuclease are analyzed at various pressures. The number of water molecules in the hydration shell increases and the hydrogen-bonded network of hydration water spans with increasing pressure. The dynamic transition of protein occurs when the spanning water network exists with the probability of about 50% and hydration water shows large density fluctuations. Formation of a spanning water network upon pressurization promotes protein dynamics as in the case of the dynamic transition with increasing hydration. Properties of hydration water in various thermodynamic states and their influence on biological function are discussed.