Microfluidic reactor for the radiosynthesis of PET radiotracers.

Here we show the first application of a microfabricated reaction system to PET radiochemistry, we term "microfluidic PET". The short half-life of the positron emitting isotopes and the trace chemical quantities used in radiolabelling make PET radiochemistry amenable to miniaturisation. Microfluidic technologies are capable of controlling and transferring tiny quantities of liquids which allow chemical and biochemical assays to be integrated and carried out on a small scale. Such technologies provide distinct advantages over current methods of PET radiochemical synthesis. To demonstrate "proof of principle" we have investigated the radiohalogenation of small and large molecular weight molecules using the microfluidic device. These reactions involved the direct radioiodination of the apoptosis marker Annexin V using iodine-124, the indirect radioiodination of the anti-cancer drug doxorubicin from a tin-butyl precursor and the radiosynthesis of 2-[(18)F]FDG from a mannose triflate precursor and fluorine-18 and hence provide a test bed for microfluidic reactions. We demonstrate the rapid radioiodination of the protein Annexin V (40% radiochemical yield within 1 min) and the rapid radiofluorination of 2-[(18)F]FDG (60% radiochemical yield within 4s) using a polymer microreactor chip. Chromatographic analysis showed that the labelling efficiency of the unoptimised microfluidic chip is comparable to conventional PET radiolabelling reactions.

Triplet energies of pi-conjugated polymers.

Using pulse radiolysis and triplet energy transfer has enabled us to measure the triplet energies in a broad range of different pi-conjugated polymers. In all cases we find that the 1 (3)B(u) is of order 0.6 to 1 eV below the 1 (1)B(u), indicative of localized triplet states with strong electron-electron correlation. We also observe that the 1 (1)A(g)-1 (3)B(u) gap decreases linearly as the 1 (1)A(g)-1 (1)B(u) gap decreases even though polymers with very different structure have been studied. This surprising result suggests that polymers with singlet gap <1.3 eV will have a triplet ground state.

Photoreactivity of biologically active compounds. XVI. Formation and reactivity of free radicals in mefloquine.

The formation and reactivity of the triplet state and free radicals of mefloquine hydrochloride (MQ) have been investigated by pulse radiolysis and flash photolysis. The excited triplet, cation radical and anion radical have been produced and their absorption characteristics determined. The triplet-triplet absorption spectrum of MQ showed a maximum at 430 nm, with a molar absorption coefficient of 3600 M(-1) cm(-1) and the quantum yield for intersystem crossing was determined to be close to unity. Deactivation of the triplet, in the absence of oxygen, led to the formation of MQ cation and/or anion radicals. The molar absorption coefficient of the cation radical at 330 nm was determined to be 2300 M(-1) cm(-1), whilst that for the anion radical was 2400 M(-1) cm(-1) at 620 nm and 3600 M(-1) cm(-1) at 350 nm. The molar absorption coefficients of the proposed neutral radical at 320 nm and 520 nm were 4000 M(-1) cm(-1) and 1300 M(-1) cm(-1) respectively. The quantum yield for the formation of singlet oxygen, sensitized by MQ triplet, was determined to be close to unity. Aqueous solutions of MQ were found to photoionize to yield hydrated electron and cation radical of MQ in a biphotonic process. The influences of pH, buffer concentration, oxygen concentration and addition of sodium azide on the formation and reactivity of the transients were evaluated. The reactions between MQ and solvated electrons and superoxide anion were also studied.

Photostability enhancement of Pyrromethene 567 and Perylene Orange in oxygen-free liquid and solid dye lasers.

We investigated the effect of oxygen on the photostability of the laser dyes Pyrromethene 567, Perylene Orange, and Rhodamine 590 by determining their longevity of laser operation when pumped by the second harmonic of aQ -switched Nd:YAG laser. In solution, dissolved oxygen accelerated the photodegradation of Pyrromethene 567 and Perylene Orange but not Rhodamine 590. The photostability of Pyrromethene 567 was also found to be dependent on the solvent and on the lifetime of singlet oxygen. Deoxygenated Pyrromethene 567 doped polycom glass and modified poly(methyl methacrylate) (MPMMA) samples were tested for longevity of laser operation. A factor of 6 improvement in photostability was found for Pyrromethene 567 in MPMMA upon deoxygenation, and the total absorbed energy per mole of dye molecules to one-half output pulse energy was 36 GJ mol-1 .

Curcumin-derived transients: a pulsed laser and pulse radiolysis study.

In this paper we report a time-resolved investigation of transients derived from curcumin, which may be intimately involved in the processes leading to its biological activity. Fluorescence and triplet quantum yields are respectively 0.06 and 0.11. The high percentage of internal conversion is proposed to proceed via H-transfer within the thermodynamically favored enol structure of what is formally a 1,3-diketone. The triplet energy (191 +/- 2 kJ mol-1), natural lifetime (1.5 microseconds) and self-quenching rate constant (5.0 x 10(8) L mol-1 s-1) have been determined. Oxygen quenching of the triplet leads to the production of singlet oxygen with unit efficiency. Curcumin quenches the latter species very inefficiently (2.5 x 10(5) L mol-1 s-1). The curcumin radical has been produced via three mechanistically distinct methods. This species is unreactive toward oxygen but is repaired by vitamins C and E and anthralin.

A pulsed laser and pulse radiolysis study of amphiphilic chlorophyll derivatives with PDT activity toward malignant melanoma.

Two amphiphilic derivatives of chlorophyll, which have high potential as photodynamic therapy sensitizers for malignant melanoma have been investigated by a combination of laser flash photolysis and pulse radiolysis. It is shown that direct excitation of monomeric forms of these molecules in both hydrophilic and hydrophobic environments produces significant yields of the corresponding triplet states, which have been characterized in terms of spectral and kinetic parameters. In both environments, scavenging of the triplets by oxygen produces singlet oxygen, O2(1 delta g), with essentially unit efficiency as evidenced by time-resolved IR luminescence measurements.

Anthralin-derived transients--II. Formation of the radical by spontaneous fragmentation of both singlet and triplet states of the 10,10'-dehydrodimer: radical pair multiplicity effects.

The singlet and triplet states of the anthralin (1,8-dihydroxy-9-anthrone) dehydrodimer have been produced selectively in benzene via pulsed laser excitation and pulse radiolysis respectively. The lifetime of S1 is less than or equal to 30 ps, that of T1 short but unspecified. Both states fragment spontaneously to yield a pair of anthralin radicals. The singlet radical pair predominantly undergoes geminate recombination within the solvent cage. In contrast, the corresponding triplet radical pair undergoes essentially exclusive cage escape to give the anthralin free radical (lambda max 370, 490 and 720 nm) which recombines under normal diffusive conditions. Both recombination processes lead, at least in part, to one or more species which have been assigned as tautomeric forms of the original dimer. The anthralin free radical in benzene is insensitive to the vitamin E model 6-hydroxy-2,2,5,7,8-pentamethylchroman and reacts only slowly with oxygen.

Anthralin-derived transients--I. The triplet state and the products of its reaction with oxygen in benzene.

Direct laser excitation in benzene of 1,8-dihydroxy-9-anthrone (anthralin) does not lead to transient species with lifetimes in the nanosecond time regime or longer. The triplet state has been produced in benzene by pulse radiolysis and characterised in terms of its absorption spectrum (lambda max 560 nm), natural lifetime (11 microseconds), self-quenching properties (kmicrosecond = 2.6 x 10(7) l mol-1 s-1) and triplet energy (234 kJ mol-1). There is no tendency in the non-polar medium for production of either the triplet or ground state in a tautomeric form. The observed triplet state reacts with oxygen with a typical rate constant, 2.2 x 10(9) l mol-1 s-1. The products of this reaction are singlet oxygen (approximately 64%) and the anthralin radical (approximately 14%).