Unusual reactivity of (6,9)purinophanes due to stereoelectronic effect

[n](6,9)Purinophanes 2a–c were synthesized and their unusual reactivity toward nucleophiles was explained by the stereoelectronic effect in the fairly rigid tetrahedral intermediate.     

The effect of lateral substitution on smectic C formation

Two related ester systems having fluoro, chloro, bromo, methyl or cyano lateral substituents have been synthesised. The effect of lateral substitution on the thermal stability of the liquid crystal phases, and particularly the smectic C phase, was examined. In some instances, a small polar group was shown to increase the stability of the smectic C phase relative to the unsubstituted analogue. The position of the lateral substituent is important. Some of the compounds exhibit a very wide smectic C phase.     

Cuprate additions to 5-methoxycyclopentenones: a novel stereoelectronic effect

Cuprate additions to 5-methoxy-2-cyclopentenone have been found to proceed with moderate to extremely high diastereofacial selectivity, depending upon the specific cuprate and reaction protocol employed. Comparisons with related 5-substituted cyclopentenones suggest that the observed selectivity is not simply steric in nature, but instead reflects a novel stereoelectronic effect.     

Conformational changes in cyclodecanone due to 2H substitution

Recently reported long-range deuterium isotope shifts of ¹³C NMR lines in [2-²H₁]cyclodecanones are simply explained on the basis of changes in the averaging of otherwise equivalent conformations.     

A new turn structure for the formation of beta-hairpins in peptides

Previous studies by Gellman and co-workers have elegantly shown that mirror-image beta-turns based upon d-Pro-Gly are especially good at stabilizing beta-hairpins and have demonstrated that peptide 1 [Arg-Trp-Gln-Tyr-Val-d-Pro-Gly-Lys-Phe-Thr-Val-Gln-NH2] folds into a well-defined beta-hairpin [Espinosa, J. F.; Gellman, S. H. Angew. Chem., Int. Ed. 2000, 39, 2330-2333]. The present study establishes that the amino acid ornithine (Orn) also forms a turn structure that is excellent at stabilizing beta-hairpins when linked through the delta-amino group and that this turn is comparable to d-Pro-Gly in ability to induce beta-hairpin formation. Thus, 1H NMR chemical shift and NOE studies establish that Orn-containing analogue 2 [Arg-Trp-Gln-Tyr-Val-deltaOrn-Lys-Phe-Thr-Val-Gln-NH2] is comparable in structure to peptide 1. The present study also establishes that the Orn turn is superior to Asn-Gly turns and that replacement of the deltaOrn with epsilonLys or d-deltaOrn generates structures that do not fold significantly.     

Reversal of low-field CIDNP due to deuterium substitution

A perturbation method is applied to the problem of low-field CIDNP. It is shown that in the intermediate magnetic field region the most important deviation from the high-field formulae is due to a perturbation of the S—T₀ mixing by interaction with the T_± levels of the radical pair. In the case of a symmetrical radical pair this contribution decreases to zero and higher order contributions become dominant. An experimental example is the reversal of low-field CIDNP of ethane formed during the thermal decomposition of acetyl peroxide compared with that of ethane-d₃ during the decomposition of acetylperoxide-d₃. A qualitative rule is given for net CIDNP effects in the intermediate field region.     

Azetidine-derived amino acids versus proline derivatives. alternative trends in reverse turn induction

The influence of 2-alkyl-2-carboxyazetidines (Aze) on the 3D structure of model tetrapeptides R2CO-2-R1Aze-l-Ala-NHMe has been analyzed by molecular modeling, 1H NMR, and FT-IR studies. The conformational constraints introduced by the four-membered ring resulted in an effective way to stabilize gamma-turn-like conformations in these short peptides. The conformational preferences of these Aze-containing peptides have been compared to those of the corresponding peptide analogues containing Pro or alpha-MePro in the place of 2-alkyl-Aze residue. In the model studied, both Pro and Aze derivatives are able to induce reverse turns, but the nature of the turn is different as a function of the ring size. While the five-membered ring of Pro tends to induce beta-turns, as previously suggested by different authors, the four-membered ring of Aze residues forces the peptide to preferentially adopt gamma-turn conformations. In both cases, the presence of an alkyl group at the alpha-position of Pro or the azetidine-2-carboxylate ring enhances significantly the turn-inducing ability. These results might open the opportunity of using 2-alkyl-Aze residues as versatile tools in defining the role of gamma-turn structures within the bioactive conformation of selected peptides, and represent an alternative to Pro derivatives as turn inducers.     

Structure formation due to antagonistic salts

Antagonistic salts are composed of hydrophilic and hydrophobic ions. In a mixture solvent (water–oil) such ion pairs are preferentially attracted to water or oil, giving rise to a coupling between the charge density and the composition. First, they form a large electric double layer at a water–oil interface, reducing the surface tension and producing mesophases. Here, the cations and anions are loosely bound by the Coulomb attraction across the interface on the scale of the Debye screening length. Second, on solid surfaces, hydrophilic (hydrophobic) ions are trapped in a water-rich (oil-rich) adsorption layer, while those of the other species are expelled from the layer. This yields a solvation mechanism of local charge separation near a solid. In particular, near the solvent criticality, disturbances around solid surfaces can become oscillatory in space. In mesophases, we calculate periodic structures, which resemble those in experiments.     

Silver(1) ion catalyzed substitution reactions: stereoelectronic control in an SN1 mechanism

Stereochemistry of the acetolysis of 4-, 6α- and 6β-bromocholest-4-en-3-ones using silver acetate was established, and the reactions were interpreted to proceed $\text{via}$ a stereoelectronically controlled S_N1 mechanism.     

Conformational and stereoelectronic investigation in 1,2-difluoropropane: The gauche effect

The effect of attaching an additional fluorine atom at C-2 in 1-fluoropropane (FP), giving 1,2-difluoropropane (DFP), on its conformational equilibrium, is theoretically evaluated. This substitution causes critical implications on the conformer stabilities of DFP (TG, GT and GG conformations) and the steric and electrostatic interactions should favor the conformer with fluorine atoms trans. However, the gauche effect plays a major role in describing the energies balance in DFP, shifting the equilibrium towards the conformation in which the two fluorine atoms are gauche. The origin of this effect is discussed through an NBO analysis, which allows the evaluation of both classical and non-classical (hyperconjugation and bent bonds) interactions as the prevailing factors governing the conformational equilibrium of molecules containing the 1,2-difluoroethane fragment.     

A measure of stereoelectronic control in the hydrolysis of an orthoester

The axial OCH₃ of 5 exchange with solvent CD₃OD up to 12 times faster than the equatorial OCH₃ group.     

Understanding the role of stereoelectronic effects in determining collagen stability. 2. A quantum mechanical/molecular mechanical study of (Proline-Proline-Glycine)(n) polypeptides

The importance of vicinal and long-range interresidue effects in determining the stability of the collagen triple helix has been investigated by quantum mechanical (QM) and molecular mechanical (MM) computations on suitable model polypeptides, taking into account solvent effects by the polarizable continuum model (PCM). At the QM level, the PII conformation corresponds to an energy minimum for pentapeptide analogues incorporating the sequence Gly-Pro-Pro-Gly, irrespective of the down or up puckering of the pyrrolidine ring. However, our computations indicate that the alternation of down and up prolines characterizing collagen and collagen-like peptides is not due to an intrinsic preference of the Pro-Pro-Gly sequence. This result is confirmed by MM computations of longer polypeptides. Next, MM computations on model triple helices show that a better packing is obtained for specific values of backbone dihedrals, which, in turn, favor the alternation of down and up prolines along each chain.     

Direct formation and site-selective elaboration of methionine sulfoximine in polypeptides

Sulfoximines are emerging moieties for medicinal and biological chemistry, due in part to their efficacy in selective inhibition of amide-forming enzymes such as γ-glutamylcysteine synthetase. While small-molecule sulfoximines such as methionine sulfoximine (MSO) and its derivatives are well studied, structures with methionine sulfoximine residues within complex polypeptides have been generally inaccessible. This paper describes a straightforward means of late-stage one-step oxidation of methionine residues within polypeptides to afford NH-sulfoximines. We also present chemoselective subsequent elaboration, most notably by copper(ii)-mediated N–H cross-coupling at methionine sulfoximine residues with arylboronic acid reagents. This development serves as a strategy to incorporate diverse sulfoximine structures within natural polypeptides, and also identifies the methionine sulfoximine residue as a new site for bioorthogonal, chemoselective bioconjugation.

Sulfoximines are emerging moieties for medicinal and biological chemistry. This work describes the late-stage incorporation of methionine sulfoximine residues into polypeptides and chemoselective subsequent elaboration of NH-sulfoximines.     

Synthesis of 2-phosphonopyrrolidine and its substitution for proline in an inhibitor of angiotensin-converting enzyme

The title compound was synthesized $\text{via}$ its diethyl ester from 1-pyrroline trimer and diethyl phosphite. The 3-mercaptopropanoyl derivative inhibited angiotensin converting enzyme with I₅₀ = 1.7 μM.     

Evidence for a stereoelectronic effect in the baeyer-villiger reaction: Introducing the intramolecular reaction

An intramolecular Baeyer-Villiger reaction has been effected involving a conformationally-fixed intermediate which breaks down with stereoelectronic control.     

Potentiometric studies on the complex formation of lanthanides with proline and hydroxyproline

The formation of the lanthanide (La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Lu) complexes with proline and hydroxyproline has been investigated by potentiometric methods as well as by a turbidimetric one which has provided some additional conclusions. It has been found that 11 and a slight amount of 21 complexes are formed. The deviation from the typical course of the formation function is discussed. It is suggested that the perturbations of complex formation in the systems are caused by hydrolysis. The stability constants of the complexes are reported.

---

Potentiometrische Untersuchungen an Lanthanid-Komplexen von Prolin und Hydroxyprolin

Zusammenfassung Die Bildung von Lanthanid-Komplexen (La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Lu) mit Prolin und Hydroxyprolin wurde potentiometrisch und mit Hilfe von Trübungsmessungen untersucht. Es wurde festgestellt, daß sich Komplexe der Zusammensetzung 11 und in kleiner Menge auch 21 bilden. Die Abweichung von typischem Verlauf der Bildungskurven wurde untersucht. Es wurde dabei festgestellt, daß für die Störungen in der Komplexbildung die Hydrolyse verantwortlich ist. Die Stabilitätskonstanten wurden bestimmt.

     

A theoretical study of the effect of silicon substitution on hydrocarbon acidity

Ab initio molecular orbital calculations with double-zeta basis sets show the relative stabilities of three tautomers on the C₂SiH₄ energy hypersurface to be 3-silapropyne > 1-silaallene > 1-silapropyne. Comparison with literature values shows 1-silaallene to be more stable than 2-silaallene. Assuming deprotonation at carbon then the order of acidity is 1-silapropyne > 10-silaallene > 3-silapropyne > silaethane > silaethylene. For silaethylene and silaethane deprotonation occurs more easily at silicon than at carbon, while for both silapropynes and 1-silaallene carbon deprotonation is slightly favoured. The α-silyl group enhances the acidity of the adjacent methyl group and a silyl group in conjugation with a carboncarbon triple bond enhances the acidity of the alkynyl proton. The methyl, ethyl, and 2-silaethyl groups all weakly decrease the acidity of the alkynyl proton.