Can we predict reactivity for aromatic nucleophilic substitution with [ 18 F]fluoride ion?

The correlation between the 13 C‐NMR chemical shift of the aromatic ring carbon bearing the leaving group and the yield of nucleophilic aromatic displacement with no‐carrier‐added [ 18 F]fluoride ion was evaluated. In comparison of structurally analogous compounds (fluoro, nitro and trimethylammonium substituted benzaldehydes, benzophenones and benzonitriles), the 13 C‐NMR chemical shift of the reactive aryl ring carbon correlated quite well with the [ 18 F]fluorination yield (r 2 =0.87) for most but not all ring structures. Compounds with trimethylammonium leaving groups or methyl ring substituents were found to not fit the proposed correlation. Kinetic studies indicated clearly different rates of reaction for these compounds, with much higher than expected reactivity for the ccompounds with the cationic leaving group. Competition experiments suggest that low reactivity of methyl‐substituted rings may be due to conversion of [ 18 F]fluoride to an unreactive form. Our results indicate that the correlation between [ 18 F]fluorination yields for nucleophilic aromatic substitution reactions and the 13 C NMR chemical shift of the aryl ring carbon bearing the leaving group is applicable to numerous structurally analogous compounds, but cannot be simply generalized to aromatic rings with different leaving groups or ring substituents.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90183/1/2580330702_ftp.pd

Oxidation of substituted 4-fluorobenzaldehydes: Application to the no-carrier-added syntheses of 4-[18F]fluoroguaiacol and 4-[18F]fluorocatechol

The synthesis of 4-[18F]fluoroguaiacol (4-[18F]fluoro-2-methoxyphenol) has been achieved in no-carrier-added form starting from 2-methoxy-4-nitrobenzaldehyde, using nucleophilic aromatic substitution by [18F]fluoride followed by Baeyer-Villiger oxidation of the benzaldehyde to the phenol. Demethylation with boron tribromide gave 4-[18F]fluorocatechol (1,2-dihydroxy-4-[18F]fluorobenzene) with an overall yield of 18-28% (EOB) in less than 2 h synthesis time. The fluorine-18 labeled intermediates and products were identical to standards of 4-fluoroguaiacol and 4-fluorocatechol prepared by the same methods. This represents a new approach to the synthesis of fluorinated phenols in fluorine-19 and fluorine-18 forms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29638/1/0000727.pd

Determining the radiation use efficiency of potato using sunshine hour data: a simple and costless approach

Aim of study: Radiation parameters and photoperiod influence potato biomass and tuber yield significantly. Lack of instrument facilities in developing countries is the main hindrance to estimate global solar radiation (GSR) and radiation use efficiency (RUE). Considering these facts, an experiment was conducted to estimate light extinction coefficient (K) and RUE using a simple but indirect approach that can be implied in any location lacking sophisticated instruments.Area of study: Field experiments were conducted in Kalyani, West Bengal, representing the Indo-Gangetic Plains.Material and methods: Angstrom-Prescott (A-P) equation was used to calculate GSR. The experiment was laid out in a split-plot design with three dates of planting (DOP), 15th Nov, 29th Nov and 13th Dec, as main plot treatment and three potato cultivars (ˈKufri Suryaˈ, ˈKufri Chandramukhiˈ and ˈKufri Jyotiˈ) as sub-plot treatment. Leaf area indices and K values were used to determine intercepted PAR (IPAR) as well as RUE.Main results: The cumulative IPAR from emergence to harvest ranged 246-429 MJ m-2 depending on planting time and varieties. Irrespective of DOPs, the highest mean RUE (4.19 g MJ-1) was calculated in ˈKufri Chandramukhiˈ, showing that it used the radiation more efficiently that the other two cultivars (ˈKufri Suryaˈ= 3.75 g MJ-1 and ˈKufri Jyotiˈ= 3.14 g MJ-1).Research highlights: Statistical indices confirmed that the A-P model can be reliably used in the study region for estimation of GSR. This simple way to estimating RUE using bright sunshine hours data can be used in developing countries, where costly radiation instruments are not available

Evaluation of age-related changes in translocator protein (TSPO) in human brain using \u3csup\u3e11\u3c/sup\u3eC-[R]-PK11195 PET

Abstract Background We studied the distribution and expression of translocator protein in the human brain using 11C-[R]-PK-11195 positron emission tomography (PK11195 PET) and evaluated age-related changes. Methods A dynamic PK11195 PET scan was performed in 15 normal healthy adults (mean age: 29 ±8.5 years (range: 20 to 49); 7 males) and 10 children (mean age: 8.8 ±5.2 years (range: 1.2 to 17); 5 males), who were studied for potential neuroinflammation but showed no focally increased PK11195 binding. The PET images were evaluated by calculating standard uptake values and regional binding potential, based on a simplified reference region model, as well as with a voxel-wise analysis using statistical parametric mapping. Results PK11195 uptake in the brain is relatively low, compared with the subcortical structures, and symmetrical. The overall pattern of PK11195 distribution in the brain does not change with age. PK11195 uptake was lowest in the frontal-parietal-temporal cortex and highest in the pituitary gland, midbrain, thalamus, basal ganglia, occipital cortex, hippocampus and cerebellum, in descending order. White matter showed negligible PK11195 uptake. Overall, brain PK11195 uptake increased with age, with midbrain and thalamus showing relatively higher increases with age compared with other brain regions. Conclusions The brain shows low PK11195 uptake, which is lower in the cortex and cerebellum compared with subcortical structures, suggesting a low level of translocator protein expression. There is no hemispheric asymmetry in PK11195 uptake and the overall pattern of PK11195 distribution in the brain does not change with age. However, brain PK11195 uptake increases with age, with the thalamus and midbrain showing relatively higher increases compared with other brain regions. This increase in uptake suggests an age-related increase in translocator protein expression or the number of cells expressing these receptors or both

Iodine-125 and fluorine-18 labeled aryl-1,4-dialkylpiperazines: Potential radiopharmaceuticals for in vivo study of the dopamine uptake system

A series of fluorine-18 and iodine-125 labeled aryl-1,4-dialkylpiperazine analogs, derivatives of GBR 12935, were synthesized as radiotracers for positron emission tomography or single photon emission computerized tomography imaging of the brain based on their affinity for the presynaptic dopamine reuptake system. High specific activity fluorine-18 tracers were prepared by nucleophilic aromatic substitution reactions; iodine-125 tracers were prepared by isotopic exchange reactions. In vitro competitive binding studies demonstrated that iodine substitution is tolerated in the 4-position of the phenyl ring of the phenalkylpiperazine group. In vivo regional brain biodistribution studies in mice indicated no selectivity of the radioiodinated ligands for the dopamine reuptake site, with striatum/cerebellum concentration ratios of 1. Similar negative results with the new fluorine-18 derivatives demonstrated that in vivo selectivity for the dopamine reuptake site appears to be critically dependent on the carbon chain length between the piperazine ring and the solitary aromatic ring. These studies suggest that development of new radiopharmaceuticals based on the GBR 12935 structure cannot be based solely on considerations of in vitro binding affinities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30090/1/0000461.pd

[18F]fluorination/decarbonylation: New route to aryl [18F]fluorides

A new route to aryl [18F]fluorides without electron withdrawing ring substituents has been developed. [18F]Fluorobenzaldehydes, prepared from no-carrier-added (NCA) [18F]fluoride using nucleophilic aromatic substitution of fluoro or nitro groups, were decarbonylated using palladium on charcoal (Pd-C). By this approach 2-methoxy-4-nitrobenzaldehyde was converted to NCA 3-[18F]fluorophenol (25-30%, EOB) and 4-fluoro-2-methoxy-5-methylbenzaldehyde to carrier-added (CA) 3-[18F]fluoro-4-methylphenol (30-40%, EOB). Overall synthesis time was about 2 h. Since the 4-fluoro-2-methoxy-5-methylbenzaldehyde was in turn prepared by methylation and regiospecific formylation of 3-fluoro-4-methylphenol, the overall process represents use of a removable activating group for nucleophilic aromatic substitution with [18F]fluoride for preparation of CA and NCA aryl [18F]fluorides.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29665/1/0000754.pd