Ab initio potential energy surface for Ar 3 +

The potential energy surface (PES) of linear Ar ₃ ⁺ is calculated at the MP4/6-31G* level including all single, double, triple and quadruple excitations. The results show that the PES of the linear Ar ₃ ⁺ has a very flat valley along the asymmetric stretching vibration normal mode, ν₃. A higher level quadratic configuration interaction calculation including single, double and triple substitutions QCISD (T) along this flat valley suggests that an asymmetric geometry energy minimum reported earlier based on MP2 [1] is due to symmetry breaking in UHF. The global minimum of the PES is found to be for the symmetric geometry atR _ab =R _bc =2.66±0.01 Å, which is in good agreement with the MRD-CI calculation [2] and expectations from our earlier photodissociation experiments [3]. The calculational results are compared with other theoretical calculations, and are discussed in the context of the photodissociation and dynamics of dissociation experiments conducted on Ar ₃ ⁺ .     

Synthetic enantiopure aziridinomitosenes: preparation, reactivity, and DNA alkylation studies

An enantiocontrolled route to aziridinomitosenes had been developed from l-serine methyl ester hydrochloride. The tetracyclic target ring system was assembled by an internal azomethine ylide cycloaddition reaction based on silver ion-assisted intramolecular oxazole alkylation and cyanide-induced ylide generation via a labile oxazoline intermediate (62 to 66). Other key steps include reductive detritylation of 26, methylation of the N-H aziridine 56, oxidation of the sensitive cyclohexenedione 68 to quinone 70, and carbamoylation using Fmoc-NCO. Although the aziridinomitosene tetracycle is sensitive, a range of protecting group manipulations and redox chemistry can be performed if suitable precautions are taken. A study of DNA alkylation by the first C-6,C-7-unsubstituted aziridinomitosene 11a has been carried out, and evidence for DNA cross-link formation involving nucleophilic addition to the quinone subunit is described.     

Synthesis,structures and mass spectrometry of lanthanide nitrate complexes with tricyclohexylphosphine oxide

The complexes Ln(NO₃)₃(OPCy₃)₃(EtOH)_x (Cy = cyclohexyl, C₆H₁₁x = 0 for Ln = Eu, Er, x = 0.5 for Ln = La, Nd and x = 1 for Ln = Tm, Yb) have been prepared by reaction of lanthanide nitrates with Cy₃PO in ethanol. The single crystal X-ray structures for Ln = La, Nd, Eu, Er, Tm and Yb are reported. The structures for Ln = La–Eu have two molecules in the unit cell in which the nitrates are all bound as bidentate ligands. The unit cell for Ln = Er contains two distinct molecules; one with three bidentate nitrates and one with two bidentate and one monodentate nitrate. The Tm and Yb complexes have one molecule in the unit cell with two bidentate and one monodentate nitrate ligands. The monodentate nitrates are hydrogen bonded to ethanol in the Tm and Yb structures but not in the Er complex. The infrared spectra of the three classes of complex do not readily permit identification of the monodentate nitrate groups. Electrospray mass spectrometry indicates that redistribution/ionisation reactions occur in solution. Ions formed by solvolysis reactions are attributed to gas phase processes associated with the electrospray technique. Tandem mass spectrometry for the La, Ho and Yb complexes shows that in the gas phase loss of Cy₃PO is the sole fragmentation pathway for all but the Yb complex where the higher energy required for initial fragmentation leads to a more complex fragmentation pattern.     

Direct assignment of the absolute configuration of a distinct class of deoxyribonucleoside cyclic N-acylphosphoramidites at phosphorus by M-GOESY nuclear magnetic resonance spectroscopy

The determination of the absolute configuration of deoxyribonucleoside cyclic N-acylphosphoramidites at phosphorus toward the synthesis of P-stereodifined phosphorothioated oligodeoxyribonucleotides is easily accomplished with computer-assisted molecular modeling and M-GOESY NMR spectroscopy. Specifically, computer-modeling diasteromeric phosphoramidite 3 has identifed a proximal (2.55 A) through-space interaction between benzylic H-5 and sugar H-2' ', which can predictably be detected by M-GOESY NMR in SP-3 but not in RP-3 because of being too distant (5.85 A). Consistent with computer-assisted modeling predictions, M-GOESY NMR spectra of SP-3 and RP-3 revealed NOE signals generated from nuclei near the selectively excited H-2' ' that are common to both SP-3 and RP-3, namely those of H-2', H-4', H-3', and H-1'. In addition, a diagnostic NOE signal at 5.5 ppm (benzylic H-5) is, as predicted, only detected in SP-3 and thus provides an unequivocal assessment of the configuration of the diastereomer at phosphorus. M-GOESY NMR data also confirm that the condensation of deoxyribonucleoside cyclic N-acylphosphoramidites with base-activated nucleosidic or nucleotidic 5'-hydroxyls proceeds via a single nucleophilic event.     

MnRe(CO)10: A review of the chemical and physical properties of a simple heterobimetallic non-bridged dimer

A review of the chemical and physical properties of MnRe(CO)₁₀ and its derivatives has been undertaken. This heterobimetallic complex is one of the simplest complexes known which contains a bond between two different metals and does not contain bridging groups. The review has revealed that high yield synthetic strategies are known for this complex and the synthetic strategies have bearing for the synthesis of other bimetallic complexes. Kinetic data suggest that information available on monometallic fragments can provide information on the reactivity trends expected for the dimer. However, the second metal is not a neutral spectator and provides a site forsecondary reactions eg for CO substitution. Data on the physical properties of the dimer are sparse and definitive statements ond _Mn-Re·v _Mn-Re, H_Mn-Re etc. cannot be made. This has significant implications for studies on related simple and complex dimer and cluster complexes.     

Comparison of capillary electrophoresis with traditional methods to analyse bovine whey proteins

The separation of the four major whey proteins by sodium dodecyl sulphate (SDS)-capillary gel electrophoresis (CGE) is described. Whilst commercially purified whey proteins could be analysed using the recommended protocol, the more complex nature of an acid whey and a reconstituted whey protein concentrate (WPC) powder necessitated considerable refinement of the CGE sample buffer. Individual whey proteins in the acid whey and WPC samples were then also separated and quantitated using capillary zone electrophoresis, polyacrylamide gel electrophoresis (PAGE) and HPLC methods and the results were compared. The values obtained for -lactalbumin (-Lac) and β-lactoglobulin (β-Lg) were consistent throughout the various methods, although size-exclusion HPLC, SDS-PAGE and SDS-CGE could not separate the two β-Lg variants or the glycosylated form of -Lac from the β-Lg. There was considerable variation in the values for the bovine serum albumin and immunoglobulin determined by the different methods and it was concluded that none of the methods could satisfactorily quantitate all four whey proteins.     

Characterization of protein-ligand interactions by high-resolution solid-state NMR spectroscopy

A novel approach for detection of ligand binding to a protein in solid samples is described. Hydrated precipitates of the anti-apoptotic protein Bcl-xL show well-resolved (13)C-(13)C 2D solid-state NMR spectra that allow site-specific assignment of resonances for many residues in uniformly (13)C-enriched samples. Binding of a small peptide or drug-like organic molecule leads to changes in the chemical shift of resonances from multiple residues in the protein that can be monitored to characterize binding. Differential chemical shifts can be used to distinguish between direct protein-ligand contacts and small conformational changes of the protein induced by ligand binding. The agreement with prior solution-state NMR results indicates that the binding pocket in solid and liquid samples is similar for this protein. Advantages of different labeling schemes involving selective (13)C enrichment of methyl groups of Ala, Val, Leu, and Ile (Cdelta1) for characterizing protein-ligand interactions are also discussed. It is demonstrated that high-resolution solid-state NMR spectroscopy on uniformly or extensively (13)C-enriched samples has the potential to screen proteins of moderate size ( approximately 20 kDa) for ligand binding as hydrated solids. The results presented here suggest the possibility of using solid-state NMR to study ligand binding in proteins not amenable to solution NMR.     

Observation of ligand binding to cytochrome P450 BM-3 by means of solid-state NMR spectroscopy

A broad understanding of the binding modes of ligands and inhibitors to cytochrome P450 is vital for the development of new drugs. We investigated ligand binding in a site-specific fashion on cytochrome P450 BM-3 from Bacillus megaterium, a 119 kDa paramagnetic enzyme, using solid-state magic angle spinning nuclear magnetic resonance methods. Selective labeling and longitudinal relaxation effects were utilized to identify the peaks in a site-specific fashion and to provide evidence for binding. Well-resolved one-dimensional and two-dimensional NMR spectra of cytochrome P450 BM-3 reveal shifts upon binding of its substrate, N-palmitoylglycine. These data are consistent with the crystallographic result that a biochemically important amino acid residue, Phe87, moves upon ligation. This experimental scheme provides a tool for probing ligand binding for complex systems.     

Intramolecular interaction effects and the structure of N2OS and N2O2: An Ab initio study

An ab initio study of O?N? N?S with full geometry optimization has been carried out to corroborate the presence of an interaction between the terminal atoms in this type of structure, which, in O?N? N?O, apparently stabilizes the cis conformer. Using the unscaled 4–31G basis set with a full set of d functions on the sulfur, there is a potential minimun at the trans but not the cis geometry. A gauche conformer with a torsional angle of 77.2° is the most stable. With N₂O₂ this basis set gives potential minima at both the cis and trans geometries, but the trans conformer is slightly more stable, contrary to experiment and the results of (7,3) basis-set calculations reported in the literature in which Gaussian lobe functions were employed. Using a (9,5) basis set there is no longer a potential minimum at the cis geometry, and a gauche structure is more stable than the cis conformer as in the case of N₂OS with the less-extended basis set. Force constants (harmonic and anharmonic), compliance constants, relaxed force constants, and interaction-displacement coordinates for both molecules are compared for key structural elements.     

A theoretical investigation into the conformational changes of dibenzo-p-dioxin, thianthrene, and selenanthrene

Theoretical ab initio calculations using the HF and B3LYP methods have been carried out to investigate the conformational differences of three cyclic rings, dibenzo-p-dioxin (DPD), thianthrene (THT), and selenanthrene (SET). The physical origin for the conformational preference of each molecule has been studied using the natural bond orbital (NBO) analysis. The NBO results indicate that DPD exists in a planar form due to strong electron delocalization caused by the specific orbital interaction, around the X atom. On the other hand, THT and SET exist as puckered forms with high inversion barriers due to less effective electron delocalization. The NBO analysis also shows that the conformational stabilization in DPD is caused by a more effective overlap of the orbitals, compared with the overlap of the orbitals in THT.