Synthesis of mesoionic[1,2,3]triazolo[5,1-d][1,2,5]triazepines

Intramolecular cyclization of 1-amino-3-phenacyl-4-carbohydrazido-1,2,3-triazolium-5-olates has been shown to take place via selective interaction of the carbonyl group with the terminal amino function of the hydrazido group to form a 1,2,5-triazepine ring. Minor products, resulting from the interaction of the α-nitrogen atom of the hydrazido group with the carbonyl function, having a N-amino-pyridazine structure were also detected and isolated. A general method for the synthesis of novel mesoionic 2-amino-7-aryl-4-oxo-2,4,5,8-tetrahydro[1,2,3]triazolo[5,1-d][1,2,5]triazepin-9-ium-3-olates was developed.     

Phase-space invariants for aggregates of particles: hyperangular momenta and partitions of the classical kinetic energy

Rigorous definitions are presented for the kinematic angular momentum K of a system of classical particles (a concept dual to the conventional angular momentum J), the angular momentum L(xi) associated with the moments of inertia, and the contributions to the total kinetic energy of the system from various modes of the motion of the particles. Some key properties of these quantities are described-in particular, their invariance under any orthogonal coordinate transformation and the inequalities they are subject to. The main mathematical tool exploited is the singular value decomposition of rectangular matrices and its differentiation with respect to a parameter. The quantities introduced employ as ingredients particle coordinates and momenta, commonly available in classical trajectory studies of chemical reactions and in molecular dynamics simulations, and thus are of prospective use as sensitive and immediately calculated indicators of phase transitions, isomerizations, onsets of chaotic behavior, and other dynamical critical phenomena in classical microaggregates, such as nanoscale clusters.     

Bound water measurements for aqueous protein solutions and food gels

The role of aqueous media in the stabilization of globular proteins and formation of gels was studied by absorption millimeter spectroscopy. This method allowed to measure bound water, the fraction of water which had decreased rotational mobility owing to the presence of solute. Hydration data for globular proteins were compared with data obtained previously for low-weight molecules and groups. It was found that rotational mobility of water molecules in the hydration shells of various kinds of solutes (groups) decreased in the following order: water structure breaking compounds>polar groups>unfolded proteins>globular proteins>non-polar groups. Time courses of the storage modulus were determined for the chemical acidification by glucono-δ-lactone (GDL) of milk samples prepared from skimmed milk powder (SMP). Gelation of unheated milk was a monotonous process that started at pH 4.9. Heat-treated milk from SMP (16 and 14 g per 100 ml) acidified by GDL (3 g per 100 ml) at 43 °C gave non-monotonous kinetics of gelation with two phases corresponding to the mechanisms induced by denatured whey proteins at pH>5 and by casein–casein interactions at pH 4.8–4.9. For heat-treated milk, measurement of bound water gave two stages of decrease in water mobility. Additional hydration of SMP during acidification gave 0.15–0.2 g and 0.8 g bound H₂O per gram of SMP for unheated and heat-treated milk, respectively.     

Synthesis of functionalized rab GTPases by a combination of solution- or solid-phase lipopeptide synthesis with expressed protein ligation

Prenylated proteins with non-native functionalities are generally very difficult to obtain by recombinant or enzymatic means. The semisynthesis of preparative amounts of prenylated Rab guanosine triphosphatases (GTPases) from recombinant proteins and synthetic prenylated peptides depends largely on the availability of functionalised prenylated peptides corresponding to the proteins' native structure or modifications thereof. Here, we describe and compare solution-phase and solid-phase strategies for the generation of peptides corresponding to the prenylated C terminus of Rab7 GTPase. The solid-phase with utilisation of a hydrazide linker emerges as the more favourable approach. It allows a fast and practical synthesis of pure peptides and gives a high degree of flexibility in their modification. To facilitate the analysis of semisynthetic proteins, the synthesised peptides were equipped with a fluorescent group. Using the described approach, we introduced fluorophores at several different positions of the Rab7 C terminus. The position of the incorporated fluorescent groups in the peptides did not influence the protein-ligation reaction, as the generated peptides could be ligated onto thioester-tagged Rab7. However, it was found that the positioning of the fluorescent group had an influence on the functionality of the Rab7 proteins; analysis of the interaction of the semisynthetic Rab7 proteins with REP (Rab escort protein) and GDI (guanosine diphosphate dissociation inhibitor) molecules revealed that modification of the peptide side chains or of the C-terminal isoprenoid did not significantly interfere with complex formation. However, functionalisation of the C terminus was found to have an adverse effect on complex formation and stability, possibly reflecting low structural flexibility of the Rab GDI/REP molecules in the vicinity of the lipid-binding site.     

Novel chemical modifications at the 4-position of chromones. Synthesis and reactivity of 4H-chromene-4-spiro-5′-isoxazolines and related compounds

Reactions of chromones with dilithiooximes proceed via nucleophilic 1,2-addition to give, on acidification, 4H-chromene-4-spiro-5′-isoxazoline derivatives in high yields. On treatment with concentrated H₂SO₄ the isoxazoline ring of this novel spiroannulated heterocyclic system opens to give α,β-unsaturated oximes, which undergo nitrosation, bromination, and the Beckmann rearrangement to the corresponding spiroisoxazolines and α,β-unsaturated amides, respectively. The latter can be obtained directly by the Beckmann rearrangement of 4H-chromene-4-spiro-5′-isoxazolines.     

Investigation of the extraction equilibrium of ternary ion-association complexes of thallium(III) with monotetrazolium salts triphenyltetrazolium chloride and thizolyl blue

The extraction equilibrium of ternary ion-association complexes obtained during the reaction of tetrachloride complex of thallium(III) and monotetrazolium salts triphenyltetrazolium chloride (TTC) or thiazolyl blue (MTT) has been studied. The optimum conditions that are required to carry out the investigations have been found. As a result of using a developed chemical model, the constants of extraction, distribution and association, the distribution coefficients and the recovery factor of investigated ionassociates have been determined radiochemically.     

Proton Relaxometry of Long-Lived Spin Order

A study of long-lived spin order in chlorothiophene carboxylates at both high and low magnetic fields is presented. Careful sample preparation (removal of dissolved oxygen in solution, chelating of paramagnetic impurities, reduction of convection) allows one to obtain very long-lived singlet order of the two coupled protons in chlorothiophene derivatives, having lifetimes of about 130 s in D₂O and 240 s in deuterated methanol, which are much longer than the T₁-relaxation times (18 and 30 s, respectively, at a field =9.4 T). In protonated solvents the relaxation times become shorter, but the lifetime is still substantially longer than . In addition, long-lived coherences are shown to have lifetimes as long as 30 s. Thiophene derivatives can be used as molecular tags to study slow transport, slow dynamics and slow chemical processes, as has been shown in recent years.     

High-performance selective excitation pulses for solid- and liquid-state NMR spectroscopy.

Computer-optimized selective pulses are routinely used in solution-state NMR spectroscopy. At the same time, their utility and importance for solid-state applications has yet to be fully realized. We suggest a new computational approach that makes the design of soft selective pulses with desired properties relatively straightforward. By applying this technique to the generic selective excitation problem, we have arrived at a family of high performance selective excitation pulses, dubbed E-Family, that allows more flexibility and better performance than analogous pulses previously reported in the literature. The new pulses have been successfully tested in both solid- and solution-state NMR experiments. A theoretical treatment of the effects of chemical shift anisotropy (CSA) on the selective excitation in magic-angle spinning (MAS) experiments in solids is presented. The set of heuristics that comprise our new strategy were incorporated into a general NMR simulation program SPINEVOLUTION.     

A facile tandem carbene-ylide route to 2-fluoropyrrole derivatives

2-Fluoropyrroles were synthesised via 1,3-dipolar cycloaddition of iminiodifluoromethanides derived from corresponding imines and difluorocarbene to dimethyl acetylenedicarboxylate.     

Structure Elucidator: a versatile expert system for molecular structure elucidation from 1D and 2D NMR data and molecular fragments

StrucEluc is an expert system that allows the computer-assisted elucidation of chemical structures based on the inputs of a series of spectral data including 1D and 2D NMR and mass spectra. The system has been enabled to allow a chemist to utilize fragments stored in a fragment database as well as user-defined fragments submitted by the chemist in the structure elucidation process. The association of fragments in this way has been shown to dramatically speed up the process of structure generation from 2D NMR data and has helped to minimize or eliminate the need for user intervention thereby further enabling the vision of automated elucidation. The use of fragments has frequently transformed very difficult 2D NMR elucidation challenges into easily solvable tasks. A strategy to utilize molecular fragments has been developed and optimized based on specific challenging examples. This strategy will be described here using real world examples. Experience gained by solving more than 150 structure elucidation problems from a variety of literature sources is also reviewed in this work.