There is considerable interest in designing synthetic catalysts that can hydrolyze phosphate diesters" -3 1 since such artificial nucleases have potential applications as novel antiviral and anticancer therapeutic agent^.[^-^] An important strategy for developing artificial enzymes is to incorporate, into a synthetic framework. functional groups known to be present in the enzyme's active site and that are essential for maintaining catalytic activity. The DNA and RNA hydrolyzing enzyme, staphylococcal nuclease (SN), contains two key arginine residues, Arg35 and Arg87, in its active site."] Site directed mutagenesis studies have establishedr8-101 that only one arginine residue (Arg35) binds to the monoanionic substrate, but both residues are required for phosphate ester hydrolysis. In an attempt to exploit this important feature of SN, weI1'l and othersr1'-'*] have designed mono-and bis(guanidinium) derivatives that bind with phosphate diesters in organic solvents. We have shown that certain bis(guanidinium) receptors can mimic SN and accelerate the transesterification of phosphate diesters. A key requirement for these guanidinium receptors[1y1 and related systemsL2, 2 0 , ''I is the addition of a general base (e.g. lutidine, tetramethylguanidine. imidazole) to deprotonate the hydroxyl nucleophile (Scheme 1 , A). In an attempt to design a receptor that contains H 0 H 02" \ Scheme 1 . Transesterification of HPNPP mediated by bis(guanidinium) receptors and an added base (A) and by a bis(guanid1nium) receptor with an appended basic group ( B i .all the necessary components for catalysis, we have linked general base groups to the bis(guanidinium) receptors. The receptor design is based on bis(a1kylguanidinium) derivatives that remain protonated in the presence of a wide range of basic groups. These receptors can potentially accelerate phosphate ester cleavage by providing a hydrogen-bonding cleft to increase the electrophilicity and facilitate nucleophilic attack on phosphorus upon binding in the manner depicted in Scheme 1, B. In this paper we report a series of alkylguanidinium ions 1-5 containing appended nitrogen bases and compare their efficiencies in accelerating the transesterification reaction of the RNA model, 2-hydroxypropyl-para-nitrophenylphosphate (HPNPP) .[22s 231 ) Telefdx. Int. code +(41?) 624-8552 [**I This work was supported by the U.S. Office of Naval Research. A n p i C'iwm. Inr. Ed. Engl. 1995, 34. N o . I 1 :<) VCH Verlugsgesrllscliu/,/r mhH, D-6Y45I Weinhein!, 1995 0570-0833iYSillll-/237 S I(J.(JO+ . 3 ; 0 C? VCH V e r l a~s~a s e l l s~~l i u~t mhH, D-69451 Wrinhrim 1995 0570-083S~9S~iiIi-1~3X S 1 O . O O i .25/0 Angeu'. Chem. In[. Ed. EngI. 1995, 34. No. I ! of HPNPP [ZY]. The rate constants were obtained by fitting at least three half-lives of the reaction according to a first-order kinetics equation. For slower reactions. rate conslants were calculated from the initial rates. First-order rate constants were calculated from the slopes of the linear plots of absorbance versus time by convertin...

A photochemical reaction, which generates surfactant molecules which then spontaneously assemble into vesicles, is described. Upon irradiation of a dispersion of the photocleavable water-insoluble precursor didecyl-2-methoxy-5-nitrophenyl phosphate, the phosphate-phenolate bond was selectively hydrolyzed and didecyl phosphate was released in the medium. Light microscopy was used to assess the presence of vesicles, which were generally in the range of 1-10 µm. This light-induced formation of vesicles is of general interest in the field of liposomes technology and may be seen as an additional contribution to the prebiotic chemistry of compartimented bilayer formation.

Metal Ion Modulation of Membrane Permeability Induced by a Polypetide Templat

No abstract

ConclusionThe geometry of trans-diphenyl(~phenyl-3-chro-manyl)methanol (II) appears to be the more diaxial for a vicinally disubstituted six-membered ring, in the absence of polar effects. Comparison with the molecular structure of trans-dimethyl 2,2'-(1,2-cyclohexylene)bis(2-methylpropanoate) (I) previously reported shows that in our compound the dihedral angle between the substituents is close to the value of 173 ° found in cyclohexane for vicinal axial C-H bonds [162(0.5) ° in II instead of 134.5(0.5) ° in I]. Furthermore, the flattening in the substituted part of the ring [endocyclic torsion angle of 55 (0-5)°1 is far less pronounced than in I [37.4 (5) °] and very close to that of cyclohexane itself (56 o).This X-ray structure determination shows also that the chroman ring of the cis isomer adopts a C(3) sofa conformation bearing the 2-phenyl substituent in axial position and the bulkier 3-substituent in an equatorial one. These two substituents are brought closer by a rather strong hydrogen bond of the OH... zr type which contributes to the rigidity of the whole molecule.We wish to thank the CNRS for financial assistance. AbstractSingle-crystal X-ray analyses of N-(4-chlorophenyl)-3-methylamino-2-nitroso-2-butenamide (I) and 5,5-dimethyl -2 -nitroso -3 -phenylamino -2 -cyclohexen -1 -one (II