Fluorine Screening

Recently, we screened riboflavin synthase (RiSy) against a small library of -containing ligands. The library encompasses about 400 ligands containing either an aromatic fluorine or a trifluoromethyl moiety. 

RiSy consists of three identical subunits denoted They form a complex of pseudo-D3 symmetry with a total molecular mass of about 75 kDa. The a-subunit (23 kDa) shows an internal sequence similarity resulting in a 26% identity of the C-and N-terminus. The N-terminal domain can be expressed separately and forms a homo-dimer that binds the substrate with a similar affinity to the complete trimeric protein.  

Several inhibitors mimicking the scaffold of lumazine (1) have been identified, but none of them consisted of new structural features. To overcome this drawback, a screening of fluorinated ligands was performed. 

The F-chemical shift was measured in advance for each member of the library. These reference experiments were carried out in D -DMSO solutions with trifluo-roethanol (TFE) as an internal standard. The 400 ligands were divided into groups of about 10-30 compounds, resulting in 15 mixtures. The combinations were chosen such as to avoid reactions and overlap of F-chemical shifts. For the composition of these mixtures, stock solutions in D -DMSO were set up and added to buffer solutions (50 mM KH2PO4, 10 mM EDTA, 10 mM Na2S03, pH 7.1). To test for binding, a portion of the stock solution was added to a solution of RiSy (0.1 mM) in the same buffer. For both samples ID F-spectra were acquired at 14.09 T (564 MHz F-frequency). 

An enzymatic assay of RiSy revealed a value of about 20-30 aM for compound 4, which could serve as a starting point for further optimizations to generate an appropriate lead structure. 

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Here we have introduced three second-rank tensors, the rotational magnetic moment tensor T2(G) and the proton and fluorine screening tensors, T2(rotational magnetic moment and chemical shift (shielding) tensors, a further term which should be included in the Zeeman Hamiltonian describes the diamagnetic susceptibility. This term takes the form... 

Since the second edition OFTHE Chemistry of Organic Fluorine Compounds Milos Hudhcky continued screening Chemical Abstracts to keep up with fluorine chem istry Some 15 000-20,000 clippings accumulated in the file cabinets in his office After his retirement, he was almost at the verge of discarding this voluminous material when it occurred to him that it could be used as a first-tier literature search for updating the book... 

Figure 5 is a section looking down through a fluorine cell perhaps 20 cm below the electrolyte level before any charge has passed. A Monel alloy screen (electrically floating) separates the fluorine from hydrogen. 

The Kel-F polychlorotrifluoroethylene view ports let us see what is happening on the hydrogen side of the screen (see later discussion). If it were really necessary to view the fluorine side, sapphire or diamond windows could probably be used. It is difficult to see below the electrolyte level of an operating cell because of gas bubbles. 

Figure 124 shows some details of the cell interior. The skirt is a solid Monel alloy sleeve extending about 2 cm below the electrolyte. (Teflon and Kel-F fluoropolymers could not be used as skirts for extended periods because they react with fluorine at the temperatures used they could probably be used as screens, however.) The screen (not shown) is an extension of the skirt. It consists of a Monel alloy sleeve with numerous 1-mm holes. The skirt and screen float electrically. They are bipolar and... 

Table 8.39 shows the main features of EDXRF. EDXRF is not able to detect the fine structure of the K, L, M, etc. lines. EDXRF is used for applications which require measurement of a limited number of elements, and where the resolution and ultralow detection limits of wavelength-dispersive systems are not necessary. For example, EDXRF has been used as a rapid screening technique for the determination of Br and Sb in plastic recyclate at a LOD of 5 ppm [230] the method was validated by means of NAA [231]. Conventional EDXRF systems and benchtop units have a limited detection capability for low-Z-elements and cannot directly measure fluorine in processing aids. 

It has also been recognized that micro-structured components, because of their low mass and thermal inertia, are able to offer short response times for unsteady state periodic operations. Micro-reactors have been used successfully for fluorination, oxidations and both heterogeneous [63-65] and homogeneous hydrogenations [66]. A review on gas-liquid micro-structured reactors has been published [67]. The very small material inventory when using micro devices offers another advantage, notably as a laboratory tool for screening applications, kinetics determination and process data acquisition, where the main concern is... 

Two independent screens have been developed to investigate the effects of fluorinated building blocks on the interactions of the dimeric peptide assembly. The impact of fluorine side chain substitutions on the stability of coiled coil folding has been studied using temperature-dependant CD spectroscopy. The second screen is based on the ability of a-helical peptides to self-replicate. Thus, peptide... 

The a-helical coiled coil-based screening system already provided a wide variety of information about the interactions of fluorinated amino acids within hydrophobic and hydrophilic protein environments. Investigations on the thermal stability as well as the replicase activity have both emphasized the orthogonal properties of fluorinated aliphatic amino acid side chains. The term orthogonal in this context has been chosen by us to demonstrate that they are in fact hydrophobic... 

Ethers and ketals in which the Rf chain is separated from the oxygen atom by two or three carbons. In spite of the screen effect due to the di- or trimethylene spacer, fluorine atoms still exert a notable effect. As in the previous case, their synthesis generally requires non conventional methods. 

Hashimoto and co-workers (139) further looked at an intermolecular carbonyl ylide cycloaddition screening several different chiral rhodium catalysts. The Hashimoto group chose to study phthaloyl amino acid derivatives for enantiocon-trol of the cycloaddition reactions (Fig. 4.8). Using fluorinated or ethereal solvents with the phthaloyl catalysts gave ee ratios of 20-69%. 

The TiOi paste is deposited onto a sheet glass (Nippon Sheet Glass, Hyogo, Japan) which has been coated with a fluorine-doped stannic oxide layer with sheet resistance of 8-10 fl/cm ) using a screen-printing technique. The resulting... 

Ulm, K. Screening Results on the Toxicity of Numerous Fluoro Organic Compounds (I), lecture given at Int. Fluorine Symp., Vancouver, 1982 see J. Fluorine Chem. 1982, 21, 69. 

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