Thiacrown Ethers Engaged C60 through Charge Transfer: Experimental and Theoretical Study.

UV-Vis spectroscopy is used to study the charge transfer complexes of thiacrown ethers 1-6 with fullerene. The size of TCE1-6 and the nature of the heteroatoms (N, O and S) have been systematically changed to examine the effect of these factors on the HOMO/LUMO energy levels, the optical energy gap and the interactions between TCE's and C60. The negative and positive values of ΔS designate the structural forming method and the randomness of the free solvent molecules, respectively. Thermodynamics and stability data show that the complexes have a 1:1 ratio that has been emphasized by density functional theory calculations. Additionally, they show a synergetic interplay of donor-acceptor, π-π, and n-π interactions, which are the basis for the affinity of our novel receptors toward C60. The proposed system of enzyme model suggests a development concept in the future design of enzyme model organic photovoltaic systems.

Synthesis of novel p-tert-butylcalix[4]arene Schiff bases and their complexes with C60, potential HIV-Protease inhibitors.

Some p-tert-butylcalix[4]arene Schiff base crown ethers were synthesized, characterized using (1)H, (13)C-NMR, DEPT 135 and Mass spectrometry. Their complexes with C60 were isolated and characterized. The inhibition effect of these complexes on HIVP was studied and found that complexes of 9 and 10 have comparable Ki values to Pepstatine which is known as HIVP inhibitor and used as a control. The synthesis of the ligands, complexes and the inhibition behavior are discussed in this article.

Genotoxicity of different tert-butylcalix[4]crowns.

The ability of two calix[4]arene derivatives, namely 25,27-p-tert-butylcalix[4]dithiooxabenzocrown (1) and 25,27-p-tert-butylcalix[4]trithiooxabenzocrown (2), to produce chromosomal aberrations in root meristematic cells of Allium cepa and micronuclei (MN) in normochromatic erythrocytes (NCE) of Balb/c mice was investigated. NCE are normal mature red blood cells with a full complement of hemoglobin but lack ribosomes. In the first test, the root tips were treated with a series of concentrations of the two test chemicals ranging from 10(-7) to 10(-4) M for 24 or 48 h. Both compounds caused concentration-dependent increases in the percentage of aberrant cells and reductions in the mitotic index. These effects depended, to some extent, on the duration of the treatment. The most conspicuous chromosomal abnormalities were c-mitosis, chromosome bridges, chromosome breaks, chromosome lags as well as micronuclei and multinuclei. In the second test, acridine orange fluorescent staining was applied to evaluate the incidence of MN in NCE of mice intraperitoneally injected with varying contents of the two test chemicals (0.02-0.08 mg/mouse). The two chemicals induced dose-dependent MN formation as compared to the negative control. The second compound had more pronounced cytogenetic influence than the first one. Mitomycin C (MMC, 14 mg/kg body weight), employed as positive control, produced more obvious effects on the parameters investigated.

The kinetics and molecular modeling of the complexation of tenoxicam with cyclodextrins in solution.

The effect of cyclodextrins on photodegradation of tenoxicam (TEN) was studied at pH 4, 7 and 10. After 60 min of irradiation with UV light, the photodegradation was extensive. All cyclodextrins (alpha, beta, or gamma) stabilize TEN and reduce the rate of photodegradation. The largest effect of cyclodextrins is at pH 7. Molecular modeling results help to explain and manipulate the results. The results are discussed and compared with other results from previous studies.

A spectrophotometric study of the charge transfer complexes of [60]fullerene with different tert-butylcalix[4]crowns.

Formation of the charge-transfer complexes between various calix[4]crowns (1-4) and [60]fullerene were studied in toluene solution using UV-vis spectrophotometry. The stability constants and the thermodynamic data of the resulting 1:1 complexes were determined and were found to decrease with increasing the size of the crown moiety of the calixcrown. Except the complex of 3, all the complexes were found to be enthalpy stabilized but disfavored in terms of entropy.

Concave polyarenes with sulfide-linked flaps and tentacles: new electron-rich hosts for fullerenes.

Pentakis(1,4-benzodithiino)corannulene (6) in CS2 formed the strongest 1:1 complexes with C60 and C70 of any corannulene derivative yet reported. The 1,3,5,7,9-pentakis(propylthio)corannulene (4b) formed weaker 1:1 complexes with C60 and C70 in CS2, whereas the decakis(propylthio)corannulene (5b) and unsubstituted corannulene (1) showed no evidence for complexation with either C60 or C70 in CS2.

UDP-N-acetylmuramic acid (UDP-MurNAc) is a potent inhibitor of MurA (enolpyruvyl-UDP-GlcNAc synthase).

Purified recombinant MurA (enolpyruvyl-UDP-GlcNAc synthase) overexpressed in Escherichia coli had significant amounts of UDP-MurNAc (UDP-N-acetylmuramic acid) bound after purification. UDP-MurNAc is the product of MurB, the next enzyme in peptidoglycan biosynthesis. About 25% of MurA was complexed with UDP-MurNAc after five steps during purification that should have removed it. UDP-MurNAc isolated from MurA was identified by mass spectrometry, NMR analysis, and comparison with authentic UDP-MurNAc. Subsequent investigation showed that UDP-MurNAc bound to MurA tightly, with K(d,UDP)(-)(MurNAc) = 0.94 +/- 0.04 microM, as determined by fluorescence titrations using ANS (8-anilino-1-naphthalenesulfonate) as an exogenous fluorophore. UDP-MurNAc binding was competitive with ANS and phosphate, the second product of MurA, and it inhibited MurA. The inhibition patterns were somewhat ambiguous, likely being competitive with the substrate PEP (phosphoenolpyruvate) and either competitive or noncompetitive with respect to the substrate UDP-GlcNAc (UDP-N-acetylglucosamine). These results indicate a possible role for UDP-MurNAc in regulating the biosynthesis of nucleotide precursors of peptidoglycan through feedback inhibition. Previous studies indicated that UDP-MurNAc binding to MurA was not tight enough to be physiologically relevant; however, this was likely an artifact of the assay conditions.

Nonenzymatic breakdown of the tetrahedral (alpha-carboxyketal phosphate) intermediates of MurA and AroA, two carboxyvinyl transferases. Protonation of different functional groups controls the rate and fate of breakdown.

The mechanisms of nonenzymatic breakdown of the tetrahedral intermediates (THIs) of the carboxyvinyl transferases MurA and AroA were examined in order to illuminate the interplay between the inherent reactivities of the THIs and the enzymatic strategies used to promote catalysis. THI degradation was through phosphate departure, with C-O bond cleavage. It was acid catalyzed and dependent on the protonation state of the carboxyl of the alpha-carboxyketal phosphate functionality, with ionizations at pK(a) = 3.2 +/- 0.1 and 4.3 +/- 0.1 for MurA and AroA THIs, respectively. The solvent deuterium kinetic isotope effect for MurA THI at pL 2.0 was 1.3 +/- 0.4, consistent with general acid catalysis. The pK(a)'s suggested intramolecular general acid catalysis through protonation of the bridging oxygen of the phosphate, though H(3)O(+) catalysis was also possible. The product distribution varied with pH. The dominant breakdown products were pyruvate + phosphate + R-OH (R-OH = UDP-GlcNAc or shikimate 3-phosphate) at all pH's, particularly low pH. At higher pH's, increasing proportions of ketal, arising from intramolecular substitution of phosphate by the adjacent hydroxyl and the enolpyruvyl products of phosphate elimination were observed. With MurA THI, the product distribution fitted to pK(a)'s 1.6 and 6.2, corresponding to the expected pK(a)'s of a phosphate monoester. C-O bond cleavage was demonstrated by the lack of monomethyl [(33)P]phosphate formed upon degrading MurA [(33)P]THI in 50% methanol. General acid catalysis through the bridging oxygen is consistent with the location of the previously proposed general acid catalyst for THI breakdown in AroA, Lys22.

Ester derivatives of hexahomotrioxacalix[3]naphthalenes: conformational and binding properties with alkali metal cations.

The syntheses of the triesters formed between ethyl bromoacetate and hexahomotrioxacalix[3]naphthalene 8, and its tert-butyl analogue 11, are described. Depending on the conditions employed, cone or partial cone conformers are produced. The conformations appear to have some influence on their complexation in neutral medium, with alkali metal cations. The X-ray structure of the partial cone triester 10 is presented.

Identification of the catalytic residues of AroA (Enolpyruvylshikimate 3-phosphate synthase) using partitioning analysis.

AroA (EPSP synthase) catalyzes carboxyvinyl transfer through addition of shikimate 3-phosphate (S3P) to phosphoenolpyruvate (PEP) to form a tetrahedral intermediate (THI), followed by phosphate elimination to give enolpyruvylshikimate 3-phosphate (EPSP). A novel approach, partitioning analysis, was used to elucidate the roles of catalytic residues in each step of the reaction. Partitioning analysis involved trapping and purifying [1-(14)C]THI, degrading it with AroA, and quantitating the products. Wild-type AroA gave a partitioning factor, f(PEP) = 0.25 +/- 0.02 at pH 7.5, where f(PEP) = [[1-(14)C]PEP]/([[1-(14)C]PEP] + [[1-(14)C]EPSP]). Eighteen mutations were made to 14 amino acids to discover which residues preferentially catalyzed either the addition or the elimination step. Mutating a residue catalyzing one step (e.g., addition) should change f(PEP) to favor the opposite step (e.g., elimination). No mutants caused large changes in f(PEP), with experimental values from 0.07 to 0.41. This implied that there are no side chains that catalyze only addition or elimination, which further implied that the same residues are general acid/base catalysts in both forward and reverse THI breakdown. Only Lys22 (protonating S3P hydroxyl or phosphate) and Glu341 (deprotonating C3 of PEP) are correctly situated in the active site. In the overall reaction, Lys22 would act as a general base during addition, while Glu341 would act as a general acid. Almost half of the mutations (eight of 18) caused a >1000-fold decrease in specific activity, demonstrating that a large number of residues are important for transition state stabilization, "ensemble catalysis", in contrast to some enzymes where a single amino acid can be responsible for up to 10(8)-fold catalytic enhancement.