Total synthesis of biseokeaniamides A–C and late-stage electrochemically-enabled peptide analogue synthesis

The first total synthesis of cytotoxic cyanobacterial peptide natural products biseokeaniamides A–C is reported employing a robust solid-phase approach to peptide backbone construction followed by coupling of a key thiazole building block. To rapidly access natural product analogues, we have optimized an operationally simple electrochemical oxidative decarboxylation–nucleophilic addition pathway which exploits the reactivity of native C-terminal peptide carboxylates and abrogates the need for building block syntheses. Electrochemically-generated N,O-acetal intermediates are engaged with electron-rich aromatics and organometallic reagents to forge modified amino acids and peptides. The value of this late-stage modification method is highlighted by the expedient and divergent production of bioactive peptide analogues, including compounds which exhibit enhanced cytotoxicity relative to the biseokeaniamide natural products.

A late-stage electrochemical decarboxylation enables rapid access to structural analogues of biseokeaniamides A–C, cytotoxic lipopeptide natural products.     

Ab initio n-electron valence state perturbation theory study of the adiabatic transitions in carbonyl molecules: formaldehyde, acetaldehyde, and acetone

The application of the recently developed second-order n-electron valence state perturbation theory (NEVPT2) to small carbonyl molecules (formaldehyde, acetaldehyde, and acetone) is presented. The adiabatic transition energies are computed for the singlet and triplet n-->pi(*), pi-->pi(*), and sigma-->pi(*) states performing a full geometry optimization of the relevant states at the single state CASSCF level and taking into account the zero point energy correction in the harmonic approximation. The agreement with the known experimental values and with previously published high level calculations confirms that NEVPT2 is an efficient tool to be used for the interpretation of molecular electronic spectra. Moreover, different insight into the nature of the excited states has been obtained. Some of the transitions presented here have never been theoretically computed previously [(3)(pi-->pi(*)) and (3)(sigma-->pi(*)) adiabatic transitions in acetaldehyde and acetone] or have been studied only using moderate level (single reference based) ab initio methods (all adiabatic transitions in acetaldehyde). In the present work a consistent disagreement between NEVPT2 and experiment has been found for the (3)(pi-->pi(*)) adiabatic transition in all molecules: this result is attributed to the low intensity of the transition to the first vibrational levels of the excited state. The n-->pi(*) singlet and triplet vertical transition energies are also reported for all the molecules.     

Microheterogeneity in aqueous-organic mixtures: thermodynamic transfer functions for benzene from water to 2-propanol aqueous systems at 25°C

The solubilities, enthalpies of solution, heat capacities, densities and ultrasonic velocities of benzene in 2-propanol-water mixtures were measured at 25°C. The apparent molal volumes, heat capacities and isentropic compressibilities and the free energies, enthalpies and entropies of transfer of benzene were calculated. The benzene concentration is sufficiently low that all thermodynamic quantities can be considered in the standard state. All these functions show large changes in the aqueous end. Large extrema are observed for 2-propanol mole fractions (X_P) near 0.08, and at higher X_P the functions rapidly tend to the values in pure 2-propanol. The free energy of transfer of benzene from water to alcohol-water mixtures decreases linearly with the alcohol concentration up to X_P of 0.07 and then more abruptly. On the other hand, at low temperature, this free energy becomes positive at low X_P. These data are consistent with the existence of microphases in 2-propanol-water mixtures for X_p>0.1. At low X_P benzene is in an aqueous medium but beyond this critical region dissolves preferentially in the organic microphases. Benzene also enhances the formation of 2-propanol microphases and this leads to the observed extrema near X_p=0.08.     

Isentropic compressibilities of alcohol-water mixtures at 25°C

The sound velocities of aqueous solutions of methanol, ethanol, 2-propanol, tertbutanol and 2-butoxyethanol (BE) were measured over the whole mole fraction range at 25°C. The isentropic apparent and partial molar compressibilities, _K,S and _S,A were derived from these data. In the case ofBE, the isothermal partial molar compressibilities were also calculated. _K,S and _S,A for all alcohols except BE initially decrease slightly with the mole fraction and then increase sharply, especially with the higher members, to the value of the pure liquid. In the case of BE, _K,S and _S,A do not go through an initial minimum and the latter goes through a sharp maximum. The compressibilities of water in these mixtures are significantly lower than those of pure water itself. These data can be correlated with other properties and are consistent with the existence of microphase transitions in these aqueous organic mixtures.     

Kondo effect in side coupled double quantum-dot molecule

Electron tunneling through a double quantum-dot molecule side attached to a quantum wire, in the Kondo regime, is studied. The mean-field finite-U slave-boson formalism is used to obtain the solution of the problem. We found conductance cancellations when the molecular energies of the side attached double quantum-dot cross the Fermi energy. We investigate the many body molecular Kondo states and its interplay with the inter-dot antiferromagnetic correlation as a function of the parameters of the system.     

Electronic Circular Dichroism Spectra of DNA Quadruple Helices Studied by Molecular Dynamics Simulations and Excitonic Calculations including Charge Transfer States

We here investigate the Electronic Circular Dichroism (ECD) Spectra of two representative Guanine-rich sequences folded in a Quadruple helix (GQ), by using a recently developed fragment diabatisation based excitonic model (FrDEx). FrDEx can include charge transfer (CT) excited states and consider the effect of the surrounding monomers on the local excitations (LEs). When applied to different structures generated by molecular dynamics simulations on a fragment of the human telomeric sequence (Tel21/22), FrDEx provides spectra fully consistent with the experimental one and in good agreement with that provided by quantum mechanical (QM) method used for its parametrization, i.e., TD-M05-2X. We show that the ECD spectrum is moderately sensitive to the conformation adopted by the bases of the loops and more significantly to the thermal fluctuations of the Guanine tetrads. In particular, we show how changes in the overlap of the tetrads modulate the intensity of the ECD signal. We illustrate how this correlates with changes in the character of the excitonic states at the bottom of the La and Lb bands, with larger LE and CT involvement of bases that are more closely stacked. As an additional test, we utilised FrDEx to compute the ECD spectrum of the monomeric and dimeric forms of a GQ forming sequence {"type":"entrez-nucleotide","attrs":{"text":"T30695","term_id":"612793"}}T30695 (5′TGGGTGGGTGGGTGGG3′), i.e., a system containing up to 24 Guanine bases, and demonstrated the satisfactory reproduction of the experimental and QM reference results. This study provides new insights on the effects modulating the ECD spectra of GQs and, more generally, further validates FrDEx as an effective tool to predict and assign the spectra of closely stacked multichromophore systems.     

Nanoparticles superficial density of charge in electric double-layered magnetic fluid: A conductimetric and potentiometric approach

We analyze potentiometric and conductimetric measurements simultaneously performed on Electric Double-Layer Magnetic Fluid based on cobalt ferrite nanoparticles, in order to obtain the pH-dependence of the particle surface charge density. We propose a mechanism for the charging of the particle surface. This model considers the ferrofluid solution as a mixture of strong and weak diprotic acids. We show how an exact analytical treatment involving proton transfer between the particle surface and the bulk solution allows the construction of a speciation diagram of the charged superficial sites. The saturation value of the superficial density of charge is found to be equal to 0.326 ± 0.065 C m^-2. Received 9 May 2001 and Received in final form 17 July 2001