Perfluoroalkylated amphiphiles with a morpholinophosphate or a dimorpholinophosphate polar head group

Some previously synthesized (perfluoroalkyl)alkyldimorpholinophosphates, CnF2n+1CmH2mOP(O)-[N(CH2CH2)(2)O](2), were found remarkably to stabilize heat sterilizable water-in-fluorocarbon reverse emulsions and to have a strong proclivity to self-aggregate into microtubular assemblies when dispersed in water. This series has now been extended in order to allow structure-property relationships to be established and product optimization to be achieved. A new series of even more fluorophilic compounds consisting in bis[(perfluoroalkyl)alkyl]monomorpholinophosphates, (CnF2n+1CmH2mO)(2)P(O)N(CH2CH2)(2)O, was also synthesized. Preliminary surfactant activity and biocompatibility data are presented and compared to data obtained with non-fluorinated analogues

Fenntartható fluoros kémia = Sustainable fluorous chemistry

(1) A „zöldebb” fluoros kémia kialakítása érdekében számos trifluormetil-csoportban gazdag reagens hatékony szintézisét dolgoztuk ki, melyek könnyen hozzáférhető szerves fluorvegyületek hasznosítására és várhatóan nagyobb környezeti lebomlási készségére hívják fel a figyelmet. (2) Eljárásokat dolgoztunk ki 3-perfluoralkil-propanol és 3-perfluoralkil-propén típusú intermedierek előállítására, illetve a köztitermékként megjelenő ún. jódhidrinek sokoldalú preparatív átalakítására. (3) Új típusú fluoros ionos folyadékokat, imidazólium-sókat és más intermediereket állítottunk elő. (4) Orosz fejlesztésű kompozit anyagokat (FUKM, FUKM-M és FUKM-MT) kémiai reagensként, illetve átmenetifém katalizátor (Pd/FUKM) hordozóként alkalmaztunk. (5) Tanulmányoztuk a Hiyama- és a Heck-kapcsolási reakciók mechanizmusát és szintetikus alkalmazhatóságát. (6) CF3I reagnest S-alkilezőszerként alkalmaztuk (7) Prof. Bühlmann al együttműködve fluoros ionofórokat és elektrokémiai szenzorokat készítettünk. (8) Azonosítottuk egy új potenciális fluorátvivő reagens molekulaszerkezeti feltételeit, melynek segítségével lehetőségünk nyílik a fluoros kémiából (fluortartalmú modulok) a fluorkémiába (szén-fluor kötesek kialakítása) átlépnünk. Ez lehetőséget ad a gyógyszerkémia számára fontos egy, kettő, vagy három fluoratomot tartalmazó vegyületek hatékony előállításához. Több közlemény csak a kövtekező évben fog megjelenni, kérem az értékelésnél ezt vegyék figyelembe. | (1) For Greener Fluorous Chemistry we developed the synthesis of several reagents from easily accessible precursor, reach in CF3-goups, which expected to have less impact and shorter environmental half-lives. (2) Novel methods for the synthesis of 3-perfluoroalkyl-propanols and –propenes were disclosed along with the uses of their synthetic intermediates. (3) New types of fluorous ionic liquids were synthesised based on imidazolium-salts. (4) Carbon-fluorinated carbon composite materials of Russian origin were applied as chemical reagents and transition metal catalyst support material (e.g. Pd/FUKM) . (5) Hiyama- and Heck-reactions with fluorous substrates were studied for a synthetic and mechanistic point of view. (6) Trifluoroiodomethane was used for improved S-alkylating processes. (7) Fluorous ionophores and electrochemical sensors were designed for the first time in co-operation with Prof. Bühlmann. (8) The structural requirements for a potential new fluorine-transfer reagent were identified and a Patentable process designed. This will allow the introduction of one, two or three fluorine atoms into target pharmaceutical molecules, and allow a shift from the fluorous to the fluorine chemistry (i.e. from F-building blocks to create C-F bonds). Please consider that some more publications are expected to appear only in the next year

Fibrinolysis in a lipid environment: modulation through release of free fatty acids

Background: Thrombolysis is conventionally regarded as dissolution of the fibrin matrix of thrombi by plasmin, but the structure of clots in vivo includes additional constituents (proteins, phospholipids) that modulate their solubilization. Objective: We examined the presence of free fatty acids in thrombi and their effects on distinct stages of fibrinolysis (plasminogen activation, plasmin activity). Methods and Results: Using the fluorescent probe acrylodated intestinal fatty acid-binding protein, variable quantities (up to millimolar concentrations) of free fatty acids were demonstrated in surgically removed human thrombi. Oleic acid at relevant concentrations reversibly inhibits more than 90% of the amidolytic activity of plasmin on a synthetic substrate (Spectrozyme PL), but only partially inhibits its fibrinolytic activity measured using turbidimetry. Chromogenic assays detecting the generated plasmin activity show that plasminogen activation by tissue-type plasminogen activator (t-PA) is completely blocked by oleic acid in the fluid phase, but is accelerated on a fibrin matrix. A recombinant derivative of t-PA (reteplase) develops higher fibrin specificity in the presence of oleic acid, because both the inhibition of plasminogen activation in free solution and its enhancement on fibrin template are stronger than with wild-type t-PA. Conclusion: Through the stimulation of plasminogen activation on a fibrin template and the inhibition of plasminogen activators and plasmin in the fluid phase, free fatty acids confine the action of fibrinolytic proteases to the site of clotting, where they partially oppose the thrombolytic barrier function of phospholipids