Peptide tic-tac-toe: heterotrimeric coiled-coil specificity from steric matching of multiple hydrophobic side chains

Specific coiled-coil heterotrimers result from steric matching of hydrophobic core side chains. A 2:1 heterotrimer is formed by peptides containing alanine or cyclohexylalanine, respectively, at a central core residue. Detailed thermodynamic analysis reveals that the designed complex is considerably more stable than the corresponding alanine homotrimer (deltaT(m) = 25 degrees C, deltadeltaG(unf) = 4.5 kcal/mol), while control complexes with naphthylalanine or cyclopropylalanine peptides are much less stable. However, the cyclohexylalanine homotrimer is of comparable stability to the 2:1 complex, prompting an investigation of multiply substituted peptides. A specific 1:1:1 heterotrimer is formed from three independent peptide strands, each bearing one large (cyclohexylalanine) and two small (alanine) side chains at the same three core positions but in different order. The combined impact of three substitutions improves specificity to the point where each pure peptide and all pairwise equimolar mixtures form significantly less stable complexes (deltaTm = 22-24 degrees C). The capacity for specific complex formation governed by multiple unnatural core side chains should facilitate design of numerous new peptide assemblies.     

Anodic stripping voltammetry of sulphide at a nickel film: towards the development of a reagentless sensor

The determination of sulphide at an electrochemically generated nickel oxide layer at glassy carbon and screen-printed electrodes in acidic media has been examined and appraised. The NiO layer was found to produce a stripping-like signal to sulphide and gave a linear peak current response from 20 to 90 μM. The response was further enhanced by repetitive cycling allowing accumulation of nickel sulphide at the electrode surface such that lower micromolar levels of sulphide (i.e. 5 μM) can be determined. The response at the NiO layer to sulphide is shown to be reproducible over a period of 24 h, thereby offering the development of a disposable amperometric sensor for sulphide.     

The de novo design of median molecules within a property range of interest

Summary In this paper an application is presented of the median molecule workflow to the de novo design of novel molecular entities with a property profile of interest. Median molecules are structures that are optimised to be similar to a set of existing molecules of interest as an approach for lead exploration and hopping. An overview of this workflow is provided together with an example of an instance using the similarity to camphor and menthol as objectives. The methodology of the experiments is defined and the workflow is applied to designing novel molecules for two physical property datasets: mean molecular polarisability and aqueous solubility. This paper concludes with a discussion of the characteristics of this method.     

Voltammetric Detection of Free Sulfhydryl Compounds in Food Flours

Cyclic voltammetry has been applied to the rapid measurement of free SH‐compounds in food flours samples. The protocol is based on the electrochemical adaptation of the Ellman's test, where the DTNB reacts with SH‐compounds present in food flour extracts, resulting in the equimolar production of the electroactive compound TNBA which, in turns, reacts with phenylendiamine. The reaction is found to provide an analytical signal from which to quantify indirectly free sulfhydryl compounds in flours extracts.     

Determination of ammonia based on the electro-oxidation of hydroquinone in dimethylformamide or in the room temperature ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide

The results detail a novel methodology for the electrochemical determination of ammonia based on its interaction with hydroquinone in DMF. It has been shown that ammonia reversibly removes protons from the hydroquinone molecules, thus facilitating the oxidative process with the emergence of a new wave at less positive potentials. The analytical utility of the proposed methodology has been examined with a linear range from 10 to 95 ppm and corresponding limit-of-detection of 4.2 ppm achievable. Finally, the response of hydroquinone in the presence of ammonia has been examined in the room temperature ionic liquid 1-ethyl-3-methylimidazolium bis(trifluormethylsulfonyl)imide, [EMIM][N(Tf)₂]. Analogous voltammetric waveshapes to that observed in DMF were obtained, thereby confirming the viability of the method in either DMF or [EMIM][N(Tf)₂] as solvent.     

Synthesis, structure, and alpha-elimination chemistry of hafnocene triarylstannyl complexes

New hafnocene triarylstannyl complexes were prepared and were shown to undergo clean thermal decompositions via alpha-aryl-elimination to produce the corresponding stannylene and a hafnocene aryl complex. The rate of the decomposition is highly dependent on the nature of the ancillary ligand, with the stabilities of the CpCp*Hf(SnPh(3))X compounds following the order X = NMe(2) > Np (alpha-agostic) > OMe > Cl > Me. Mechanistic information suggests that alpha-aryl-elimination may be viewed as a concerted process involving nucleophilic attack of the migrating aryl group onto the electrophilic metal center.     

Simultaneously multiply-configurable or superposed molecular logic systems composed of ICT (internal charge transfer) chromophores and fluorophores integrated with one- or two-ion receptors

Integrated "ICT chromophore-receptor" systems show ion-induced shifts in their electronic absorption spectra. The wavelength of observation can be used to reversibly configure the system to any of the four logic operations permissible with a single input (YES, NOT, PASS 1, PASS 0), under conditions of ion input and transmittance output. We demonstrate these with dyes integrated into Tsien's calcium receptor, 1-2. Applying multiple ion inputs to 1-2 also allows us to perform two- or three-input OR or NOR operations. The weak fluorescence output of 1 also shows YES or NOT logic depending on how it is configured by excitation and emission wavelengths. Integrated "receptor(1)-ICT chromophore-receptor(2)" systems 3-5 selectively target two ions into the receptor terminals. The ion-induced transmittance output of 3-5 can also be configured via wavelength to illustrate several logic types including, most importantly, XOR. The opposite effects of the two ions on the energy of the chromophore excited state is responsible for this behaviour. INHIBIT and REVERSE IMPLICATION are two of the other logic types seen here. Integration of XOR logic with a preceding OR operation can be arranged by using three ion inputs. The fluorescence output of these systems can be configured via wavelength to display INHIBIT or NOR logic under two-input conditions. The superposition or multiplicity of logic gate configurations is an unusual consequence of the ability to simultaneously observe multiple wavelengths.     

Macrocyclic cobalt(III) complexes as precursors for metal-polythiophene hybrid materials

A thiophene-functionalised macrocyclic ligand trans-6,13-dimethyl-6-((thiophen-3-ylmethyl)amino)-1,4,8,11-tetraazacyclotetradecane-13-amine (L¹) has been prepared and complexed with Co^III. The ligand L¹ binds as a pentadentate in the crystallographically characterised complexes [CoL¹(OAc)](ClO₄)₂ and [CoL¹Cl]Cl₂. Electro-copolymerisation of [CoL¹Cl]Cl₂ with 3,4-ethylenedioxythiophene (EDOT) in a 1:2 ratio on a preformed poly-3,4-ethylenedioxythiophene (PEDOT) film resulted in metal–polymer hybrid films of high quality, consistency and uniformity in appearance. The copolymerised films were characterised by XPS indicating a 1:11 ratio of incorporation of complex to EDOT. Electrochemistry of the Co-PEDOT film (cast on an indium-doped tin oxide working electrode) in water revealed a Co^III/II redox couple at a potential ca. −600 mV (vs Ag/AgCl) which is similar to that seen in solution for the monomeric aqua complex [CoL¹(OH₂)]³⁺.     

Chemistry of constrained dioxocyclam ligands with Co(III): unusual examples of C-H and C-N bond cleavage

The reactions between H(2)dc3 and Co(acac)(3) have been studied in the presence and absence of base. In the presence of base, a complex with an intramolecular Co-C bond, Co(dc3-C-(8))(H(2)O), 1, is formed, presumably through heterolytic C-H bond activation. An X-ray crystallographic study demonstrates the presence of a Co-C bond and shows that the diazacyclooctane (daco) subunit adopts the chair-boat conformation with respect to the metal. The cobalt-carbon bond induces strain in the macrocycle as demonstrated by bond angles significantly deviating from tetrahedral. The (13)C NMR resonance of the carbon atom bound to cobalt (-10.5 ppm) suggests significant ionic character in the cobalt-carbon bond. However, we were unable to cleave this bond in the presence of strong acid. In the absence of base, the reaction of Co(acac)(3) with H(2)dc3 resulted in C-N cleavage of the ligand and the formation of a complex of dioxocyclam, Co(dc)(acac), 2. This complex has subsequently been prepared in high yield by the reaction of Co(acac)(3) with dioxocyclam. An X-ray crystallographic study demonstrates that dioxocyclam adopts the heretofore unreported cis configuration, having folded along a N-Co-N axis that is perpendicular to the Co-acac plane.     

Efficient and practical Ag-catalyzed cycloadditions between arylimines and the Danishefsky diene

An efficient Ag-catalyzed method for asymmetric addition of the Danishefsky diene to various aryl imines to afford cycloadducts in > or =89% ee and > or =85% isolated yield is reported. Reactions are effected with 0.1-1 mol % catalyst (4 degrees C), and the chiral ligand is readily prepared from commercially available materials, including the inexpensive i-Leu. These catalytic asymmetric cycloadditions can be carried out without the use of solvent or with undistilled THF in air. A first generation supported chiral catalyst that effectively promotes the cycloaddition reaction and can be recycled (five cycles) is described.