Fluorophosphates

Calcium is a metallic element, fifth in abundance in the earth s crust, of which if forms more than 3%. It is an essential constituent of leaves, bones, teeth, and shells. Never found in nature uncombined, it occurs abundantly as limestone, gypsum, and fluorite. Apatite is the fluorophosphate or chlorophosphate of calcium. 

In the geochemistry of fluorine, the close match in the ionic radii of fluoride (0.136 nm), hydroxide (0.140 nm), and oxide ion (0.140 nm) allows a sequential replacement of oxygen by fluorine in a wide variety of minerals. This accounts for the wide dissemination of the element in nature. The ready formation of volatile silicon tetrafluoride, the pyrohydrolysis of fluorides to hydrogen fluoride, and the low solubility of calcium fluoride and of calcium fluorophosphates, have provided a geochemical cycle in which fluorine may be stripped from solution by limestone and by apatite to form the deposits of fluorspar and of phosphate rock (fluoroapatite [1306-01 -0]) approximately CaF2 3Ca2(P0 2 which ate the world s main resources of fluorine (1). 

Phosphoms oxyfluoride is a colorless gas which is susceptible to hydrolysis. It can be formed by the reaction of PF with water, and it can undergo further hydrolysis to form a mixture of fluorophosphoric acids. It reacts with HF to form PF. It can be prepared by fluorination of phosphoms oxytrichloride using HF, AsF, or SbF. It can also be prepared by the reaction of calcium phosphate and ammonium fluoride (40), by the oxidization of PF with NO2CI (41) and NOCl (42) in the presence of ozone (43) by the thermal decomposition of strontium fluorophosphate hydrate (44) by thermal decomposition of CaPO F 2H20 (45) and reaction of SiF and P2O5 (46). 

Other uses of Snp2 are in the synthesis of fluorophosphate glasses having low melting temperatures (13—15), in formation of transparent film (16), and in the preparation of optically active alcohols (17). 

FLUOROALUMINATES, FLUOROBERYLLATES, FLUOROPHOSPHATES, FLUOROSILICATES, AND SIMILAR ENTRIES. 

Mode of Action. The fluoride ion inhibits enzymes, such as enolase, which require Mg as a prosthetic group, by precipitating a complex magnesium fluorophosphate thus it prevents phosphate transfer in oxidative metaboHsm. 

The farther into the uv and the narrower the distribution of the resonant electron frequencies, the smaller the effect of dispersion in the visible region. The Pb(II) ion exhibits absorption in the near-uv, and addition of Pb(II) to a glass increases both n and dispersion. However, the use of Ba(II) and La(III) increases n without increasing dispersion. Fluorophosphates, having absorption bands located well into the uv, are examples of glasses with high AbbH numbers and low refractive indexes. 

Bu4N F , THF, Pyr, H2O, rt, 30 min. These conditions result in the formation of a mixture of fluorophosphate and phosphate. In the case of oligonucleotides, some intemucleotide bond cleavage is observed with this reagent. 

Reaction of dibenzofuran, ferrocene, and aluminum powder in the presence of aluminum chloride with subsequent hydrolysis and precipitation of the hexa-fluorophosphate salt gives 34 [80JOM(186)265]. When ferrocene and aluminum chloride are in excess, dicationic complexes 35 result. The reaction leading to 36 was also reported [84JOM(260)105]. 

The mixture was then cooled to 20°C and 19 gallons of benzene was added. This was followed by the introduction of 123.5 lb (2.80 Ib-mols) of dry powdered sodium fluoride (95% pure). The mixture was stirred and heated to the refluxing temperature in a period of 1 hour and held at this temperature (95° to 98°C) for 4 hours. The product obtained was cooled and filtered to yield a filter cake which was washed with three 5-gallon portions of benzene. The filtrate and washing were then combined and distilled under reduced pressure. There was obtained 158 lb (74% yield of theory based on PCI3) of diiso-propyl fluorophosphate, 8P 62°C at 9 mm and 46°C at 5 mm. 

Synthesis of aziridines by treatment of carbenes with imines was reported by Jacobsen [56]. A metallocarbene 104 derived from ethyl diazoacetate and copper fluorophosphate was treated with N-arylaldimines to form aziridines with reasonable diastereoselectivities (>10 1 in favor of cis) but with low enantioselectivities (about 44% ee). This was shown to result from a competitive achiral reaction path-... 

Inhibitors which interact only with peptidases of one catalytic type include pepstatin (aspartic peptidases) E64 (cysteine peptidases from clan CA) diisopropyl fluorophosphates (DFP) and phenylmethane sulfonyl-fluoride (PMSF) (serine peptidases). Bestatin is a useful inhibitor of aminopeptidases. 

The most recognized toothpaste ingredient is probably the class of compounds known as fluorides. Stannous fluoride was the first to be used in toothpaste because, unlike sodium fluoride, it did not lose its effectiveness when combined with the abrasive most common at the time, calcium phosphate. Later, sodium mono-fluorophosphate came into popular use because it too could be used with the common abrasives. 

Diethylenetriaminepentaacetic acid DFMO al-Difluoromethyl ornithine DFP Diisopropyl fluorophosphate DFX Desferrioxamine DGLA Dihomo-y-linolenic acid DH Delayed hypersensitivity DHA Docosahexaenoic acid DHBA Dihydroxybenzoic acid DHR Delayed hypersensitivity reaction... 

The different coordination behaviour of F- and 0-ligands in the [P03F] ion becomes evident in the interesting structural isomery of (NH4)2P03F H2O (26) and (NH4)2S03 H2O (28) also, the stmctural parameters of which are very much alike -the part of the F-atom in the fluorophosphate being played by the lone electron pair in the sulfite ion. 

The unsoluble fluorophosphates can be prepared from the sodium salt by reaction with heavy metal nitrates, whereas the watersoluble salts are appropriately prepared by the reaction of the sligthly soluble AgjPOjF with heavy metal chlorides (24). Acid salts M H[P03F] with = Na, K, NH4 result from fractional precipitation by addition of alcohol and ether to the aqueous solution of the free acid (17). Further methods for the synthesis of fluorophosphates are given by Eqs. (12) and (13), which lead to dimethylin fluorophosphate (32) and to tin (II) difluorophosphate (55) ... 

More complicated are fluorination reactions of phosphorus pentoxide with NH F 34) and NaHp2 (55) yet they are suited for the preparation of fluorophosphates on large scale ... 

An n.m.r. study of the permutational isomerisations within a series of amidium fluorophosphates (133) has revealed an irregular mechanism with dissociation of the P-N and also the P-0 bonds of the bidentate ligands and the formation of five-coordinate intermediates (134)61. Reversible intramolecular migrations of pentaco-ordinate phosphorus in the N-C-N triad of amidines (e.g. 135, 136,... 

Organophosphorus esters are known to react with a serine hydroxyl group in the active site of the acetylcholinesterase protein (Ecobichon 1991 Murphy 1986). Some organophosphorus esters (e.g., diisopropyl fluorophosphate, [DFP]) bind irreversibly, while others bind in a slowly reversible fashion, thereby leading to a slow reactivation (dephosphorylation) of the enzyme. A process known as "aging" has also been described in which reversibly bound compounds are changed with time to moieties that are essentially irreversibly... 

Fluorophosphates (phosphorfluoridates), which are important for backbone modified oligonucleotides in molecular biology, are generally synthesized from phosphoric imi-dazolides or triazolides and acylfluorides. In these reactions, for example, the azole group (of the phosphoric or phosphinic imidazolide) is substituted by a fluorine atom, forming an acylazole compound as by-product.[202],[2033... 

Recently a very mild method was discovered for the synthesis of dinucleoside fluorophosphates in the conversion of a dinucleoside phosphite with iV V -oxalyldiimi-dazole into the corresponding phosphoric imidazolide, which is then treated with acyl fluoride [204] <202]... 

The power of the pooled GST fusion protein approach will increase as new biochemical reagents and assays become available. The development of chemical probes for biological processes, termed chemical biology, is a rapidly advancing field. For example, the chemical synthesis of an active site directed probe for identification of members of the serine hydrolase enzyme family has recently been described (Liu et al., 1999). The activity of the probe is based on the potent and irreversible inhibition of serine hydrolases by fluorophosphate (FP) derivatives such as diisopropyl fluorophosphate. The probe consists of a biotinylated long-chain fluorophosphonate, called FP-biotin (Liu et al., 1999). The FP-biotin was tested on crude tissue extracts from various organs of the rat. These experiments showed that the reagent can react with numerous serine hydrolases in crude extracts and can detect enzymes at subnanomolar... 

---