Theoretical study of the excited singlet and triplet states of alloxan

The possibility of excited‐state protomeric shifts in the biologically important molecule, alloxan, is investigated. We have focused on the S₁ and T₁ excited states of alloxan and its hydroxy tautomers. Modifications brought in by excitation on the relative stabilities, activation barriers, and optimized geometries, computed at the MNDO, AM1, and PM3 levels of approximation, have been discussed for both excited electronic states. The absorption and fluorescence spectra for the three tautomers are also discussed. Results show significant changes in the geometries on excitation, although the changes are similar for the singlet and triplet excited states. Though the relative stability orders do not change, the 2‐hydroxy tautomer is stabilized, while the 4‐hydroxy tautomer gets destabilized on excitation. The excited states are (n,π*) states, involving the promotion of a nonbonding oxygen lone pair from the CO? CO? CO moiety, which explains why the oxygens of this group become less basic and the 4‐hydroxy tautomer gets destabilized on excitation. However, the activation barriers do not reduce significantly on excitation, and this precludes the possibility of ground‐ or excited‐state proton transfer in the gas phase. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001     

Development and validation of a RP-HPLC method for Roflumilast and its degradation products

Roflumilast is a phosphodiesterase type 4 inhibitor that is administered orally as a long-term, in the clinical treatment of chronic obstructive pulmonary disease and asthma. Launched in 2010 for the European market, it currently does not have an official monograph. Here, a reproducible gradient RP-HPLC method was developed and validated for the separation and determination of Roflumilast in the presence of its six major degradation products. Separation was performed on a C₁₈ analytical column (250?×?4.6?mm, 5?µm) with a mobile phase-A of ACN and a phase-B of ammonium acetate buffer (5?mM, pH 4.2) containing triethylamine (0.5% v/v). The most effective RP-HPLC gradient program was determined to be 0/80, 35/10, 36/80, 40/80 (time in minutes/% mobile phase-B). The flow rate was 1.0?ml/min and the column temperature was 25°C. The success of separation of the degradation products with different chemical characteristics was obtained by extending the time of the gradient, changing the proportion of the mobile phases and increasing the velocity of the flow. Two detectors were evaluated for the identification of degradation products and Roflumilast: a diode-arrary detector and a charged aerosol detector. The inability of the charged aerosol detector to dectect one of the six degradation products indicated that the method developed with RP-HPLC and the diode-array detector was more suitable for Roflumilast analysis. The method was validated according to specificity, linearity, LOD, LOQ, accuracy, precision and robustness.     

Comparative study of separation and determination of triazines by micellar electrokinetic capillary chromatography and nonaqueous capillary electrophoresis: application to residue analysis in natural waters

The separation and determination of a mixture of chloro- and methylthiotriazines in water samples by both micellar electrokinetic capillary chromatography (MEKC) and nonaqueous capillary zone electrophoresis (NA-CZE) were compared. The characteristics of both methods proved to be very similar in terms of separation efficiency and analysis times, but application of these methods for the analysis of triazines in natural waters, with a prior preconcentration step, revealed significant differences. A preconcentration step by solid-phase extraction (SPE) with Oasis HLB cartridges was accomplished for the determination of triazines at sub-ppb levels in drinking and river waters; when NA-CZE was used after this SPE step, electropherograms with fewer interferences and more stable baselines were obtained than when separation was carried out using MEKC. Another aspect related to the application to real samples was the lack of precision encountered upon evaluating the electrophoretic signals generated when using SPE coupled with NA-CZE. Here, we demonstrate the importance of choosing an appropriate internal standard for analyte quantification. It is recommended that a triazine belonging to the same family as that of the triazine to be determined should be used as internal standard.     

Desulfation and rearrangement of tigemonam to an isoxazolidin-5-one and the synthesis of the rearrangement product

The β-lactam antibiotic Tigemonam 2 undergoes desulfation to the N-hydroxyazetidinone 4 , which rearranges to the isoxazolidin-5-one 6 . The structure of the rearrangement product 6 was confirmed by synthesis.     

Experimental and theoretical characterization of arsenite in water: insights into the coordination environment of As-O

Long-term exposure to arsenic in drinking water has been linked to cancer of the bladder, lungs, skin, kidney, nasal passages, liver, and prostate in humans. It is therefore important to understand the structural aspects of arsenic in water, as hydrated arsenic is most likely the initial form of the metalloid absorbed by cells. We present a detailed experimental and theoretical characterization of the coordination environment of hydrated arsenite. XANES analysis confirms As(III) is a stable redox form of the metalloid in solution. EXAFS analysis indicate, at neutral pH, arsenite has a nearest-neighbor coordination geometry of approximately 3 As-O bonds at an average bond length of 1.77 A, while at basic pH the nearest-neighbor coordination geometry shifts to a single short As-O bond at 1.69 A and two longer As-O bonds at 1.82 A. Long-range ligand scattering is present in all EXAFS samples; however, these data could not be fit with any degree of certainty. There is no XAS detectable interaction between As and antimony, suggesting they are not imported into cells as a multinuclear complex. XAS results were compared to a structural database of arsenite compounds to confirm that a 3 coordinate As-O complex for hydrated arsenite is the predominate species in solution. Finally, quantum chemical studies indicate arsenite in solution is solvated by 3 water molecules. These results indicate As(OH)3 as the most stable structure existing in solution at neutral pH; thus, ionic As transport does not appear to be involved in the cellular uptake process.     

Elevated-temperature metathesis syntheses of structurally novel alkali-metal tetrakis(3,5-di-tert-butylpyrazolato)lanthanoidate(III) complexes: toluene-coordinated discrete bimetallic complexes and supramolecular chains

Sodium and potassium tetrakis(3,5-di-tert-butylpyrazolato)lanthanoidate(III) complexes [M[Ln(tBu(2)pz)(4)]] have been prepared by reaction of anhydrous lanthanoid trihalides with alkali metal 3,5-di-tert-butylpyrazolates at 200-300 degrees C, and a 1,2,4,5-tetramethylbenzene flux for M=K. On extraction with toluene (or occasionally directly from the reaction tube) the following complexes were isolated: [Na(PhMe)[Ln(tBu(2)pz)(4)]] (1 Ln; 1 Ln=1 Tb, 1 Ho, 1 Er, 1 Yb), [K(PhMe)[Ln(tBu(2)pz)(4)]].2 PhMe (2 Ln; 2 Ln=2 La, 2 Sm, 2 Tb, 2 Ho, 2 Yb, 2 Lu), [Na[Ln(tBu(2)pz)(4)]](n) (3 Ln; 3 Ln=3 La, 3 Tb, 3 Ho, 3 Er, 3 Yb), [K[Ln(tBu(2)pz)(4)]](n) (4 Ln; 4 Ln=4 La, 4 Nd, 4 Sm, 4 Tb, 4 Ho, 4 Er, 4 Yb, 4 Lu), with the last two classes generally being obtained by loss of toluene from 1 Ln or 2 Ln, and [Na(tBu(2)pzH)[Ln(tBu(2)pz)(4)]].PhMe (5 Ln; 5 Ln=5 Nd, 5 Er, 5 Yb). Extraction with 1,2-dimethoxyethane (DME) after isolation of 2 Ho yielded [K(dme)[Ho(tBu(2)pz)(4)]] (6 Ho). X-ray crystal structures of 1 Ln (=1 Tb, 1 Ho; P2(1)/c), 2 Ln (=2 La, 2 Sm, 2 Tb, 2 Yb, 2 Lu; Pnma), 3,4 Ln (=3 La, 3 Er, 4 Sm; P2(1)/m), and 5 Ln (=5 Nd, 5 Er, and 5 Yb; P1) show each group to be isomorphous regardless of the size of the Ln(3+) ion. All complexes contain eight-coordinate [Ln(eta(2)-tBu(2)pz)(4)] units. These are further linked to the alkali metal by bridging through two (1,2,5 Ln) or three (3,4 Ln) tBu(2)pz groups which show striking coordination versatility. Sodium is coordinated by an eta(4)-PhMe, a micro-eta(2):eta(2)-tBu(2)pz, and a micro-eta(4)(Na):eta(2)(Ln)-tBu(2)pz ligand in 1 Ln, and by one eta(1)-tBu(2)pzH and two micro-eta(3)(Na):eta(2)(Ln) ligands in 5 Ln. By contrast, potassium has one eta(6)-PhMe and two micro-eta(5)(K):eta(2)(Ln) ligands in 2 Ln. Classes 3,4 Ln form polymeric chains with the alkali metal bonded by two micro-eta(3)(NNC-M):eta(2)(Ln)-tBu(2)pz ligands within [MLn(tBu(2)pz)(4)] units which are joined together by eta(1)(C)-tBu(2)pz-Na, K linkages.     

New artificial receptors from selectively functionalized calix[4]arenes

Abstract

The development of new synthetic methods for the monoalkylation of calix[4]arenes at the lower rim allows the synthesis of a new class of trihydroxamate siderophores. Three chelating hydroxamic acid units are introduced through a sequence of reactions which blocks the macrocycle in the cone conformation. The new ligands obtained form neutral 1:1 complexes (FeL) with iron (III), which are stable in EtOH/H₂O 9:1 at pH 2–7. Calix[4]arene bis-crown ethers are prepared by exploiting the selective 1,2-(proximal) functionalization of calix[4]arenes at the lower rim. These ligands are, however, less effective in complexing alkali metal cations compared with the 1,3-calix[4]arene crown-ethers which, in their partial cone structure, offer a better shielding for the complexed cations. Rigid upper rim-bridged calix[4]arenes potentially useful for the inclusion of neutral molecules are prepared by exploiting the selective 1,3-diformylation of calix[4]arene at the upper rim. Finally a new chloromethylation method for calix[4]arenes blocked in the cone conformation is described together with the synthesis of new cavitands.