Gelation or molecular recognition; is the bis-(α,ß-dihydroxy ester)s motif an omnigelator?

Understanding the gelation of liquids by low molecular weight solutes at low concentrations gives an insight into many molecular recognition phenomena and also offers a simple route to modifying the physical properties of the liquid. Bis-(α,ß-dihydroxy ester)s are shown here to gel thermoreversibly a wide range of solvents, raising interesting questions as to the mechanism of gelation. At gelator concentrations of 5-50 mg ml⁻¹, gels were successfully formed in acetone, ethanol/water mixtures, toluene, cyclohexane and chloroform (the latter, albeit at a higher gelator concentration). A range of neutron techniques - in particular small-angle neutron scattering (SANS) - have been employed to probe the structure of a selection of these gels. The universality of gelation in a range of solvent types suggests the gelation mechanism is a feature of the bis-(α,ß-dihydroxy ester) motif, with SANS demonstrating the presence of regular structures in the 30-40 Å range. A correlation between the apparent rodlike character of the structures formed and the polarity of the solvent is evident. Preliminary spin-echo neutron scattering studies (SESANS) indicated the absence of any larger scale structures. Inelastic neutron spectroscopy (INS) studies demonstrated that the solvent is largely unaffected by gelation, but does reveal insights into the thermal history of the samples. Further neutron studies of this kind (particularly SESANS and INS) are warranted, and it is hoped that this work will stimulate others to pursue this line of research.

Synthesis of bioorthogonal and crosslinking amino acids for use in peptide synthesis.

The ability to incorporate non-canonical amino acids into proteins by genetic or chemical methods allows one to introduce novel chemical properties into a protein at a defined residue. Such a residue may then be modified using common organic transformations. In this way, the structure or function of the peptide may be altered without perturbing any of the other neighbouring amino acids in the peptide chain. Here, we describe the syntheses and potential applications of multiple para-substituted phenylalanine derivatives comprising an isothiocyanate, α-diazoketone, or nitrone functionality. In all, three novel amino acids were synthesized in good overall yields. These non-canonical amino acids permit the further development of in vitro and in vivo chemoselective and regioselective bioconjugate reactions not possible with other reagents.

Evaluation of electronics, electrostatics and hydrogen bond cooperativity in the binding of cyanide and fluoride by Lewis acidic ferrocenylboranes.

Synthetic approaches based on the direct borylation of ferrocene by BBr(3), followed by boryl substituent modification, or on the lithiation of ferrocene derivatives and subsequent quenching with the electrophile FBMes(2), have given access to a range of ferrocene derivatized Lewis acids with which to conduct a systematic study of fluoride and cyanide binding. In particular, the effects of borane electrophilicity, net charge, and ancillary ligand electronics/cooperativity on the binding affinities for these anions have been probed by a combination of NMR, IR, mass spectrometric, electrochemical, crystallographic, and UV-vis titration measurements. In this respect, modifications made at the para position of the boron-bound aromatic substituents exert a relatively minor influence on the binding constants for both fluoride and cyanide, as do the electronic properties of peripheral substituents at the 1'- position (even for cationic groups). By contrast, the influence of a CH(2)NMe(3)(+) substituent in the 2- position is found to be much more pronounced (by >3 orders of magnitude), reflecting, at least in part, the possibility in solution for an additional binding component utilizing the hydrogen bond donor capabilities of the methylene CH(2) group. While none of the systems examined in the current study display any great differentiation between the binding of F(-) and CN(-) (and indeed some, such as FcBMes(2), bind both anions with equal affinity within experimental error), much weaker boronic ester Lewis acids will bind fluoride (but give a negative response for cyanide). Thus, by the incorporation of an irreversible redox-matched organic dye, a two-component [BMes(2)/B(OR)(2)] dosimeter system can be developed capable of colorimetrically signaling the presence of fluoride and cyanide in organic solution by Boolean AND/NOT logic.

Facile syntheses of dissymmetric ferrocene-functionalized Lewis acids and acid-base pairs.

A facile synthetic approach is reported for the synthesis of dissymmetric 1,2-ferrocenediyl Lewis acids and mixed acid-base pairs including the first example of a 1-phosphino-2-borylferrocene; the use of non-racemic electrophiles allows for the isolation of single diastereomer products.

Metal-catalyzed cycloisomerization reactions of cis-4-hydroxy-5-alkynylpyrrolidinones and cis-5-hydroxy-6-alkynylpiperidinones: synthesis of furo[3,2-b]pyrroles and furo[3,2-b]pyridines.

Furo[3,2-b]pyrroles and furo[3,2-b]pyridines can be conveniently prepared in good yields from the cycloisomerization reactions of cis-4-hydroxy-5-alkynylpyrrolidinones and cis-5-hydroxy-6-alkynylpiperidinones, respectively, using Ag(I), Pd(II)/Cu(I), or Au(I) catalysis. In one case, the cycloisomerization product was unstable and produced a furan derivative by a ring-opening reaction.

Self-assembling chiral gelators for fluorinated media.

Formulations involving partially and fully fluorinated media represent a technological challenge given the lipophobic and hydrophobic nature of such liquids. The identification of self-associating materials with which to control the viscosity and solubilizing characteristics of fluorinated solvents is a particularly interesting area of research. It is shown here that the presence of the stereogenic centers inherent in a family of bis-(alpha,beta-dihydroxy ester)s is an essential requirement for the thermoreversible gelation of mixtures of partially fluorinated liquids 2H,3H-perfluoropentane (HPFP) and 1H,1H-heptafluorobutanol (HFB). Gelation is driven by hydrogen bonding, which induces a nonpreferred conformation around the bis-(alpha,beta-dihydroxy ester) structural motif. An analysis of the melting temperature yields an enthalpy of melting that is consistent with three to four hydrogen bonds, commensurate with the end-group structure of the gelator. Small-angle neutron scattering demonstrated the existence of the common fibrillar structures whose dimensions showed no obvious correlation with the molecular structure of the gelator.

Diastereoselective Ritter reactions of chiral cyclic N-acyliminium ions: synthesis of pyrido- and pyrrolo[2,3-d]oxazoles and 4-Hydroxy-5-N-acylaminopyrrolidines and 5-hydroxy-6-N-acylaminopiperidines.

Pyrido- and pyrrolo[2,3-d]oxazoles can be conveniently prepared in high yield from the Ritter reaction of nitriles and in situ generated chiral cyclic N-acyliminium ions. cis-4-Hydroxy-5-acylaminopyrrolidines and cis-5-hydroxy-6-acylaminopiperidines can be readily obtained by acid hydrolysis of these bicyclic heterocyclic compounds, respectively.