Sulfur Ligands. from β-Lactam Antibiotics to Contrast Agents for MRI

Abstract

NMR, IR and semi empirical Molecular Orbital PM3 studies on selected β-lactam antibiotics are reported. The role of sulfur in β-lactam antibiotics is discussed.     

The use of β-ketothioesters for the exceptionally mild preparation of β-ketoamides

Transamination of t-butylacetothioacetate derivatives with primary and secondary amines in the presence of silver (I) trifluoroacetate gives high yields of the correspondingβ-ketoamides.     

Analytical Study of β-Irradiated Antibiotics in the Solid State

This paper reports results of the study on the influence of β-irradiation on the physical and chemical properties of selected salts of β-lactam antibiotics in solid state (sodium salt: ampicillin, azlocillin, benzylpenicillin, carbenicillin and piperacillin; potassium salt of benzylpenicillin, ampicillin anhydricum, ampicillin trihydricum, amoxicillin trihydricum and bacampicillin hydrochloride). The source of irradiation was a linear accelerator of electrons, and the irradiation effects were checked on the basis of the following: determination of mass, melting point and water contrent, and spectrophotometric (UV, IR) chromatographic and thermal (DTG, DSC) studies. This revised version was published online in August 2006 with corrections to the Cover Date.     

The search for a new model structure of β-Factor XIIa

We present the search for a new model of -factor XIIa, a blood coagulation enzyme, with an unknown experimental 3D-structure. We decided to build not one but three different models using different homologous proteins as well as different techniques and different modellers. Additional studies, including extensive molecular dynamics simulations on the solvated state, allowed us to draw several conclusions concerning homology modelling, in general, and -factor XIIa, in particular.     

The Driving Force for the Acylation of β-Lactam Antibiotics by L,D-Transpeptidase 2: Quantum Mechanics/Molecular Mechanics (QM/MM) Study

β-lactam antibiotics, which are used to treat infectious diseases, are currently the most widely used class of antibiotics. This study focused on the chemical reactivity of five- and six-membered ring systems attached to the β-lactam ring. The ring strain energy (RSE), force constant (FC) of amide (C−N), acylation transition states and second-order perturbation stabilization energies of 13 basic structural units of β-lactam derivatives were computed using the M06-2X and G3/B3LYP multistep method. In the ring strain calculations, an isodesmic reaction scheme was used to obtain the total energies. RSE is relatively greater in the five-(1a–2c) compared to the six-membered ring systems except for 4b, which gives a RSE that is comparable to five-membered ring lactams. These variations were also observed in the calculated inter-atomic amide bond distances (C−N), which is why the six-membered ring lactams C−N bond are more rigid than those with five-membered ring lactams. The calculated ΔG^# values from the acylation reaction of the lactams (involving the S−H group of the cysteine active residue from L,D transpeptidase 2) revealed a faster rate of C−N cleavage in the five-membered ring lactams especially in the 1–2 derivatives (17.58 kcal mol⁻¹). This observation is also reflected in the calculated amide bond force constant (1.26 mDyn/A) indicating a weaker bond strength, suggesting that electronic factors (electron delocalization) play more of a role on reactivity of the β-lactam ring, than ring strain.     

The Calicheamicins, A Family of Extremely Potent Antitumor Antibiotics

The calicheamicins, produced by Micromonospora echinospora ssp. calichensis, were discovered in afermentation products screening program for DNA-damaging antitumor agents. Seven related com-ponents were isolated and characterized. The chemical structure of the major component, calicheam-icin γ_1~1, containing a bicyclic enediyne system, was determined by a combination of degradation stud-     

On The Fluorometric Method for the Measurement of β-Cyanoalanine Synthase Activity

Abstract

A modification of a fluorescence assay method for β-cyanoalanine synthase has been described which involves the direct coupling of the product of cyanide and cysteine to resazurin, to produce the fluorescent resosurfin, The fluorescence produced was found to be directly proportional to the rate of the reaction.     

The Preparation of β-Hydroxysulfoxides

. Oxidation of β-hydroxy thioethers with MnO₂-aqu. 35%/HCl in methanol gives β-hydroxy sulfoxides in high yields.     

Pyrrolidine synthons for β-lactams

Fused tricyclic aziridines, methyl rel-(2R,2aR,3R,4R,4aR,4bS)- and rel-(2S,2aR,3R,4R,4aR,4bS)-4-hydroxy-2,4a-dimethoxyhexahydro-1-oxa-2b-azacyclopropa[cd]pentalene-3-carboxylates, have been synthesized as possible precursors to β-lactams. The product structure has been determined by two-dimensional NMR techniques in combination with computational methods.     

The Triangle-relationship of β-lactam Antitiotics

The geometric parameters for D-Ala-D-Ala are optimized by MM, the most and next two stable conformations are obtained. According to the interaction model with target emzyme suggested by us, the traingle-relationship of it is obtained. This triangle-relationship could be found in the pharmaceuticals belong to different classes of β-actams also.     

On A Safe and Practical Method for The Preparation of β-Keto Phosphonates1

Acylations of the magnesium enolate derivatives of trimethyl and triethylphosphonoacetates, using a magnesium chloride-triethylamine system, lead to 2-acylphosphonoacetates which are decarbalkoxylated to give β-keto phosphonates.     

The salt effect for the solubilities of metal β-diketonates—II: Beryllium benzoylacetonate

In order to confirm extensively a generalized interpretation for the salt effect in solvent extraction of metal chelates, the solubilities of bis(1-phenyl-1,3-butanedionato) Be(II) (Be(bzac)₂) in aqueous solutions of LiCl, NaClO₄, NaNO₃, KBr, NaBr, KCl, NaCl and Na₂SO₄ were determined at 25°C. The salting coefficients of these salts for Be(bzac)₂ were obtained from the above data, and were found to accord with McDevit-Long equation except for LiCl. The salting-in effect of LiCl is discussed from the aspect of the strong hydration of small Li⁺ ion. The salting coefficients for Be(bzac)₂ are compared with those for the corresponding copper chelate (Cu(bzac)₂) and an influence of the stereochemical configurations of the metal chelates on the salt effect is also discussed.     

Amine-promoted β-elimination of a β-aryloxy aldehyde for fluorogenic chemodosimeters

We previously reported a fluorescent chemodosimeter for ozone. The β-elimination step after the ozonolysis of the chemodosimeter was too slow to be practical for real-time monitoring of ozone. We examined primary, secondary, and tertiary amines at various pHs. It was found that pyrrolidine in pH 9 buffer could accelerate the elimination to generate a fluorescence signal. The elimination step is now sufficiently rapid to monitor ozone exposure in real time. We also discovered that azetidine was distinctly effective for the same elimination reaction in a pH 6 buffer.     

Can Eucalyptol Replace Antibiotics?

One of the primary reasons for the search for new antimicrobial agents is the increasing and spreading resistance of microorganisms to previously used drugs. This is particularly important in the case of rapidly progressing infections that require the rapid administration of an appropriately selected antibiotic. However, along with the administration of antibiotics, complications in the disease-weakened body may arise in the form of systemic mycoses, viral infections, and protozoan infections. Therefore, there is an increasing interest among researchers focusing on the use of naturally occurring terpenic compounds in stand-alone or combined therapies with antibiotics. In this publication, the aim of our work is to present the results of a literature review on the antimicrobial activity of eucalyptol.     

The first ionic liquid-promoted three-component coupling strategy for an expeditious synthesis of β-nitrocarbonitriles/thiocyanates

A novel and convenient three-component coupling reaction of nitromethane, aromatic aldehydes and trimethylsilyl cyanide (TMSCN) or ammonium thiocyanate has been developed for an expeditious synthesis of β-nitrocarbonitriles or β-nitrothiocyanates, respectively, via C-C and C-S bond-forming reactions. The synthetic protocol strategically involves a one-pot sequential Henry reaction and a Michael addition efficiently promoted by the same ionic liquid [bmim]OH. The main advantages of the present approach include the use of inexpensive simple substrates and an ionic liquid as an efficient reaction promoter for the mild synthesis in a one-pot procedure.     

The Interaction of β-Cyclodextrin with Benzoic Acid

The interaction of β-cyclodextrin with benzoic acid was studied by UV and IR spectroscopy, X-ray diffraction, and thermogravimetry. The introduction of the benzoic acid molecule into the internal hydrophobic β-cyclodextrin cavity and additional stabilization by weak H-bonds caused the formation of 1: 1 axial inclusion complexes of the host—guest type. The degree of crystallinity of the inclusion complex decreased compared with the initial compounds, whereas its thermal stability increased.     

The application of β-cyclodextrin derivative functionalized aligned carbon nanotubes for electrochemically DNA sensing via host-guest recognition

We functionalized aligned carbon nanotubes (ACNTs) electrode with a new kind of β-cyclodextrin (β-CD) derivative through diazotization reaction. The resulting β-CD/ACNTs electrode was used to detect DNA hybridization in homogeneous solution based on host–guest recognition technology. In the sensing protocol, one special DNA probe was designed with a stem-loop structure and both ends modified, which we called dually labeled DNA probe (DLP). One end of the DLP was labeled with dabcyl as guest molecule for β-CD/ACNTs electrode capture, and the other end was labeled with a CdS nanoparticle as an electrochemical tag to indicate the occurrence of DNA hybridization. In the absence of the target DNA sequence, the DLP maintains its hairpin structure in solution phase and would not be captured and detected by the β-CD/ACNTs electrode. In the presence of the complementary target sequence, the conformational structure of the DLP was altered and a double-stranded DNA (dsDNA) molecule was formed by the hybridization of DLP and complementary DNA sequence. Consequently, the dsDNA was captured by the β-CD/ACNTs electrode owing to guest–host recognition between β-CD and dabcyl. The electrochemical signal from the CdS nanoparticle–dsDNA/β-CD/ACNTs was then measured. Under optimized detection conditions, the proposed method showed high sensitivity and selectivity with a detection limit of 5.0 × 10⁻¹³ M for complementary DNA sequence.     

Fluorescent Mesoporous Nanoparticles for β-Lactamase Screening Assays

We present a sensitive and rapid screening method for the determination of β-lactamase activity of antibiotic-resistant bacteria, by designing a pH-sensitive fluorescent dye-doped mesoporous silica nanoparticle encapsulated with penicillin G as a substrate. When penicillin G was hydrolysed by β-lactamase and converted into penicilloic acid, the acidic environment resulted in fluorescence quenching of the dye. The dye-doped mesoporous nanoparticles not only enhanced the β-lactamase-catalyzed reaction rate but also stablized the substrate, penicillin G, which degrades into penicilloic acid in a water solution without β-lactamase. Twentyfive clinical bacterial samples were tested and the antibiotic resistant and susceptible strains were identified. The proposed method may detect the presence of β -lactamases of clinically relevant samples in less than 1 hour. Moreover, the detection limit of β-lactamase activity was as low as 7.8×10⁻⁴ U/mL, which was determined within two hours.