Showing papers by "J. Fraser Stoddart published in 1987"

Complexation of Paraquat and Diquat by a bismetaphenylene-32-crown-10 derivative

Abstract: U.v. and 1H n.m.r. spectroscopic studies in solution on the 1:1 complexes both [Paraquat][PF6]2 and [Diquat][PF6]2 form with the bismetaphenylene-32-crown-10 derivative (BMP32C10), supported by X-ray crystal structures on the free BMP32C10 and [Diquat·BMP32C10][PF6]2·Me2CO, provide further fundamental understanding of the electronic and steric nature of the intermolecular noncovalent interactions that are essential to the successful design and synthesis of a molecular receptor for optimal binding of the [Paraquat]2+ dication.

Complexation of Diquat by a bisparaphenylene-34-crown-10 derivative

Abstract: The Paraquat dication forms a 1:1 molecular inclusion complex both in acetone solution and in the solid state with the bisparaphenylene-34-crown-10 derivative (BPP34C10) as a result of intra-complex stabilisation from charge transfer interactions as well as from hydrogen and electrostatic bonding.

Complex formation between bisparaphenylene-(3n+4)-crown-n ethers and the paraquat and diquat dications

Abstract: U.v. and n.m.r. spectroscopic investigations in solution have been employed to assess the ability of a series (n= 7–12) of bisparaphenylene-(3n+ 4)-crown-n ethers to form stable 1:1 complexes with [Diquat]2+ and [Paraquat]2+ dications; these mappings of molecular recognition are supported by fast atom bombardment mass spectrometry of the 1:1 complexes with both [Diquat][PF6]2 and [Paraquat][PF6]2, and a single crystal X-ray structure analysis of [Diquat·BPP31C9][PF6]2.

Noncovalent Bonding Interactions between Tetraphenylborate Anions and Paraquat and Diquat Dications

Abstract: A ternary complex - in solution and in the crystal - with - charge transfer interactions is formed be the dication paraquat (MeNC5H4C5H4NMe) and two tetraphenylborate anions. This involves face-to-face and face-to-edge interactions between pyridinium rings and phenyl rings. Scarcely more than a methyl group of the flat paraquat is discernable in the illustration on the right.

Structural mapping of an unsymmetrical chemically modified cyclodextrin by high-field nuclear magnetic resonance spectroscopy

Abstract: Samples of 2,6-per-O-methyl-s-cyclodextrin (DMsCD), prepared according to literature procedures, have been shown to be less than 70% pure. The major impurity has been identified as the unsymmetrical over-methylated cyclodextrin derivative (DM+1)sCD. Samples of pure DMsCD and (DM+1)sCD have been prepared by (i) benzoylating a chromatographically homogeneous mixture obtained after methylating sCD with dimethyl sulphate, (ii) separating chromatographically the resulting DMsCD heptabenzoate (DMsCD-B7) and (DM+1)sCD hexabenzoate [(DM+1)sCD-B6], and then (iii) subjecting the pure perbenzoates to de-O-benzoylation. Both DMsCD-B7 and (DM+1)sCD-B6 have been fully characterised. High-resolution 1H and 13C n.m.r. spectroscopy, with use of modern pulse techniques (homonuclear double resonance difference spectroscopy, COSY, J-resolved, JMOD, XHCORRD, and CHORTLE) for signal assignment and n.O.e. difference spectroscopy for residue sequencing, has been used to assign individually (i) 41 out of the 49 heterotopic protons and (ii) 29 out of the 42 heterotopic carbon atoms of the unsymmetrical (DM+1)sCD-B6(nuclei associated with O-methyl and O-benzoyl groups were excluded from consideration). The complete spectroscopic characterisation of unsymmetrical chemically modified cyclodextrins is important in the investigation of these compounds as potential enzyme models. The necessity of preparing pure chemically modified cyclodextrin derivatives cannot be over-emphasised.

The dependence of the solid state structures of bisparaphenylene-(3n+ 4)-crown-n ethers upon macrocyclic ring size

Abstract: X-Ray crystallography on the free BPP(3n+4)Cn ethers where n= 7,8,10,11, and 12 reveals a conformational dependence for the macrocycles which is reflected in their cavity sizes, with a maximum for n= 10, and in the relative orientations of the two hydroquinol rings, almost orthogonal for n= 7 and parallel or nearly parallel for n= 8,10,11, and 12, with respect to each other.

A comparison of the receptor stereochemistry in [Pt(bipy)(NH3)2·dinaphtho-30-crown-10][PF6]2 and [Diquat·dinaphtho-30-crown-10][PF6]2(bipy = 2,2′-bipyridine)

Abstract: X-Ray crystallography and 1H n.m.r. spectroscopy have revealed dramatic differences in the binding of [Pt(bipy)(NH3)2]2+ and [Diquat]2+ dications by dinaphtho-30-crown-10 (DN30C10) with the platinum complex adopting a slewed position, apparently in order to maximise overlap between the π-arene systems in the receptor and in the complex, whereas the Diquat dication adopts a symmetrical position more consistent with maximisation of Coulombic interactions.

The extramolecular chemical approach to enzyme analogues

Abstract: result and others obtained with the various analogues suggest that, while enzyme-substrate hydrogen bonding may play a role in the A-kinase catalysed phosphoryl group transfer reactions, the a-N-methylated and depsi-containing peptide 1 analogues react at relative rates which require additional explanations. Among the explanations for our results that must be considered are the possibilities that the substitutions of N-methyl groups in the amide bonds cause disruptive peptide-enzyme steric interactions or that intrapeptide steric interactions could prevent a particular peptide analogue from assuming the conformation recognizable by A-kinase. The nature of such steric interactions has been probed in the second aspect of our work (Bramson et al., 1987) which is briefly described herein. As already mentioned, by means of studies utilizing n.m.r. spectroscopy evidence has been obtained that A-kinase probably binds Leu-Arg-Arg-Ala-Ser-Leu-Gly, peptide 1, in one of two extended coil conformations (A or B, described by Rosevear et al., 1984). We have considered, therefore, the possibility that the relative reactivities of a series of N-methylated peptides based on the structure of peptide 1 might be related to the ease with which each peptide can assume the A or B Conformation. The N-methylated peptides which we examined are those illustrated in Table 1 and also the additional ones illustrated in Table 2. Utilizing computer graphics, on the basis of estimates of the magnitude of the steric interactions that would be induced by N-methylation of the amide groups in peptide 1 derivatives locked in either conformation, the ability of each peptide analogue to form a particular conformation was predicted. We found that there was a good correlation between the catalytic activity of A-kinase in the phosphorylation of the N-methylated peptides and the ability of each peptide to form conformation A but not B. To test these findings further we probed the possibility that the reactivity of a relatively unreactive N-methylated peptide might be partially restored by a second change which allowed the peptide to assume conformation A. The finding that such restoration could be achieved together with our other results suggests that when peptide 1 is bound in the enzymic active site it has a conformation which resembles structure A much more closely than structure B (Bramson et al., 1987). In the third aspect of our work we have probed whether when other protein kinases are observed to catalyse the phosphorylation of the same peptide sequences as does A-kinase, the protein kinases utilize the same conformation of the peptide in their reactions (Thomas et al., 19873). We have employed, therefore, the reactions of the conformationally restricted N-methylated peptides which have been utilized as substrates for A-kinase in examining the conformational requirements of the cyclic GMP-dependent protein kinase (G-kinase). The G-kinase is homologous in sequence to A-kinase (Taiko et al., 1984) and has comparable substrate specificities (Lincoln & Corbin, 1977). Our kinetic results with the N-methylated peptides show that, despite the ability of the G-kinase to bind the peptides in a conformation resembling that of conformation A, the Genzyme is more tolerant of backbone methylation than in A-kinase. As a result, while the reactivity of the G-kinase with the prototypic peptide substrate Leu-Arg-Arg-Ala-SerLeu-Gly, peptide 1, is about 10-fold less than the reactivity with the A-kinase, as assessed from the relative magnitudes of k,,,/K,, when the parent peptide was N-methylated at the amide group of the Ser’ residue, the resultant peptide substrate was at least 700-fold more reactive with G-kinase than with A-kinase. Our observations with the peptide which is N-methylated at the phosphorylatable serine residue of peptide 1 show that backbone methylation can represent an approach to making peptide substrates which are selective for a particular kinase (Thomas et al., 19873). This finding encourages us to pursue the possibility that N-methylation of peptides might provide a method for targeting peptidebased inhibitors to selected protein kinases. Partial support of this research by National Institutes of Health Grant GM 32204 is gratefully acknowledged.