Synthetic studies in the alkaloid field—IV: The sodium dithionite reduction of 1-[2-(3-indolyl)-ethyl]-3-methoxycarbonyl pyridinium bromides

The preparation of racemic indolo[2,3-a]quinolizine derivatives by sodium dithionite reduction of appropriate pyridinium bromides has been studied, A method has been found of influencing with high degree of stereoselectivity the C(12b)-C(2) stereochemical relationship in the products formed. The determination of the stereochemistry of the products by comparative examination of their ¹³C NMR spectra is described. The convenience of the sodium dithionite reduction method for the preparation of vallesiachotamine 1 models is discussed.     

Efficient red light photo-uncaging of active molecules in water upon assembly into nanoparticles

We introduce a means of efficiently photo-uncaging active compounds from amino-1,4-benzoquinone in aqueous environments. Aqueous photochemistry of this photocage with one-photon red light is typically not efficient unless the photocaged molecules are allowed to assemble into nanoparticles. A variety of biologically active molecules were functionalized with the photocage and subsequently formulated into water-dispersible nanoparticles. Red light irradiation through various mammalian tissues achieved efficient photo-uncaging. Co-encapsulation of NIR fluorescent dyes and subsequent photomodulation provides a NIR fluorescent tool to assess both particle location and successful photorelease.     

Two-way photoswitching using one type of near-infrared light, upconverting nanoparticles, and changing only the light intensity

Only one type of lanthanide-doped upconverting nanoparticle (UCNP) is needed to reversibly toggle photoresponsive organic compounds between their two unique optical, electronic, and structural states by modulating merely the intensity of the 980 nm excitation light. This reversible "remote-control" photoswitching employs an excitation wavelength not directly absorbed by the organic chromophores and takes advantage of the fact that designer core-shell-shell NaYF(4) nanoparticles containing Er(3+)/Yb(3+) and Tm(3+)/Yb(3+) ions doped into separate layers change the type of light they emit when the power density of the near-infrared light is increased or decreased. At high power densities, the dominant emissions are ultraviolet and are appropriate to drive the ring-closing, forward reactions of dithienylethene (DTE) photoswitches. The visible light generated from the same core-shell-shell UCNPs at low power densities triggers the reverse, ring-opening reactions and regenerates the original photoisomers. The "remote-control" photoswitching using NIR light is as equally effective as the direct switching with UV and visible light, albeit the reaction rates are slower. This technology offers a highly convenient and versatile method to spatially and temporally regulate photochemical reactions using a single light source and changing either its power or its focal point.     

In vivo visible light-triggered drug release from an implanted depot

Controlling chemistry in space and time has offered scientists and engineers powerful tools for research and technology. For example, on-demand photo-triggered activation of neurotransmitters has revolutionized neuroscience. Non-invasive control of the availability of bioactive molecules in living organisms will undoubtedly lead to major advances; however, this requires the development of photosystems that efficiently respond to regions of the electromagnetic spectrum that innocuously penetrate tissue. To this end, we have developed a polymer that photochemically degrades upon absorption of one photon of visible light and demonstrated its potential for medical applications. Particles formulated from this polymer release molecular cargo in vitro and in vivo upon irradiation with blue visible light through a photoexpansile swelling mechanism.     

A molecular dynamics investigation of the influence of hydration and temperature on structural and dynamical properties of a dimyristoylphosphatidylcholine bilayer

A series of molecular dynamics simulations of dimyristoylphosphatidylcholine bilayers, with different levels of hydration and temperature, were performed to examine the influence of hydration on properties of lipid membranes. Structural and dynamical properties such as area per lipid, electron densities, order parameters for all CH bonds and water, diffusion, and reorientation autocorrelation functions were determined and were all found to be affected by changes in the hydration level. The simulations give an overall picture of the bilayer going to a more ordered state when the hydration level is reduced. Lipid headgroups were found to adopt an orientation more parallel to the membrane plane when the water content was decreased. Dynamical properties such as lipid diffusion and relaxation of reorientation time correlation functions were found to become slower with the removal of water. Our simulation results generally agree with experimental data in cases where such data are available. One important conclusion drawn is that while structural properties are affected only moderately dynamical properties are affected very strongly by a decrease of water content.     

The Phloroglucinols of Dryopteris aitoniana PICHI SERM. (Dryopteridaceae,Pteridophyta)

The phenolic compounds of the fern Dryopteris aitoniana were analyzed by improved methods avoiding alcaline reagents and contact with unbuffered SiO₂, which can cause deterioration. We confirmed the presence of five of the formerly (1971) reported six compounds, while the sixth, formerly incorrectly assumed to be aspidin (based on a spot in TLC), has now been isolated as cristals (TR-1579). It has the empirical formula C₂₇H₅₂O₂, but its structure is still unknown. Five other compounds were isolated in pure form, tetra-albaspidin BBBB ( 25 -BBBB) a known but rare phloroglucinol, and four new compounds: penta-albaspidin BBBBB ( 37 -BBBBB), hexa-albaspidin BBBBBB ( 38 -BBBBBB), tetraflavaspidic acid BBBB ( 26 -BBBB) and hexaflavaspidic acid BBBBBB ( 39 -BBBBBB). The structures were established by degradation NMR and partly by field-desorption and fast-atom-bombardment (FAB) mass spectra. The oligoflavaspidic acids are very unstable compounds, deteriorating during isolation procedures using the older ‘standard method’.     

Multimodal fluorescence modulation using molecular photoswitches and upconverting nanoparticles

The intensity and colour of the light emitted from upconverting nanoparticles is controlled by the state of photoresponsive dithienylethene ligands decorated onto the surface of the nanoparticles. By selectively activating one or both ligands in a mixed, 3-component system, a multimodal read-out of the emitted light is achieved.     

Modification of the CHARMM force field for DMPC lipid bilayer

The CHARMM force field for DMPC lipids was modified in order to improve agreement with experiment for a number of important properties of hydrated lipid bilayer. The modification consists in introduction of a scaling factor 0.83 for 1-4 electrostatic interactions (between atoms separated by three covalent bonds), which provides correct transgauche ratio in the alkane tails, and recalculation of the headgroup charges on the basis of HF/6-311(d,p) ab-initio computations. Both rigid TIP3P and flexible SPC water models were used with the new lipid model, showing similar results. The new model in a 75 ns simulation has shown a correct value of the area per lipid at zero surface tension, as well as good agreement with the experiment for the electron density, structure factor, and order parameters, including those in the headgroup part of lipids.