Noncovalent interaction-driven stereoselectivity of copper(II) complexes with cyclodextrin derivatives of L- and D-carnosine

L-Carnosine (β-alanyl-L-histidine, LCar) is the most widely and abundantly distributed copper(II)-coordinating endogenous dipeptide. Though its physiological role has not been completely understood yet, many functions have been proposed for this compound. LCar might be crucial in the potential reduction or prevention of several pathologies in which the metal ions are thought to be involved. The potential therapeutic applications of LCar are drastically limited because of hydrolysis by specific dipeptidases (carnosinases). D-Carnosine (DCar), the enantiomer of the naturally occurring dipeptide, shows the same properties as those of LCar, but it is not hydrolyzed by carnosinases. Chemical modification of LCar has been proposed as a promising strategy to reduce its enzymatic hydrolysis; conjugation of a carbohydrate moiety may also improve site-specific transport to different tissues, which would enhance the peptide bioavailability. On this basis, we have functionalized DCar with β-cyclodextrin (CDDCar) and characterized the compound via NMR. The copper(II) binding properties of the new DCar derivative were investigated by spectroscopic techniques (UV-vis, circular dichroism, electron paramagnetic resonance) and potentiometric measurements. The results surprisingly revealed a pronounced difference from the analogous LCar derivative (CDLCar), especially concerning the dimeric species. The spectroscopic data show that this stereoselectivity is driven by noncovalent interactions, namely, hydrogen bonds, CH-π interactions, and steric and hydrophobic effects of the cyclodextrin cavity.     

Structure and C-S bond cleavage in aryl 1-methyl-1-arylethyl sulfide radical cations

Steady state and laser flash photolysis (LFP) of a series of p-X-cumyl phenyl sulfides (4-X-C(6)H(4)C(CH(3))(2)SC(6)H(5): 1, X = Br; 2, X = H; 3, X = CH(3); 4, X = OCH(3)) and p-X-cumyl p-methoxyphenyl sulfides (4-X-C(6)H(4)C(CH(3))(2)SC(6)H(4)OCH(3): 5, X = H; 6, X = CH(3); 7, X = OCH(3)) has been carried out in the presence of N-methoxy phenanthridinium hexafluorophosphate (MeOP(+)PF(6)(-)) under nitrogen in MeCN. Steady state photolysis showed the formation of products deriving from the C-S bond cleavage in the radical cations 1(+?)-7(+?) (2-aryl-2-propanols and diaryl disulfides). Formation of 1(+?)-7(+?) was also demonstrated by LFP experiments evidencing the absorption bands of the radical cations 1(+?)-3(+?) (λ(max) = 530 nm) and 5(+?)-7(+?) (λ(max) = 570 nm) mainly localized in the arylsulfenyl group and radical cation 4(+?) (λ(max) = 410, 700 nm) probably mainly localized in the cumyl ring. The radical cations decayed by first-order kinetics with a process attributable to the C-S bond cleavage. On the basis of DFT calculations it has been suggested that the conformations most suitable for C-S bond cleavage in 1(+?)-4(+?) and 7(+?) are characterized by having the C-S bond almost collinear with the π system of the cumyl ring and by a significant charge and spin delocalization from the ArS ring to the cumyl ring. Such a delocalization is probably at the origin of the observation that the rates of C-S bond cleavage result in very little sensitivity to changes in the C-S bond dissociation free energy (BDFE). A quite large reorganization energy value (λ = 43.7 kcal mol(-1)) has been calculated for the C-S bond scission reaction in the radical cation. This value is much larger than that (λ = 12 kcal mol(-1)) found for the C-C bond cleavage in bicumyl radical cations, a reaction that also leads to cumyl carbocations.     

ATRP, subsequent azide substitution and 'click' chemistry: three reactions using one catalyst in one pot

This communication describes a novel and fast reaction to substitute the living chain end after Atom Transfer Radical Polymerization (ATRP) by an azide functionality. The reaction is catalyzed by the ATRP catalyst at room temperature in aqueous solution and can be followed by a 'click' reaction using again the same catalyst.     

Enantio and diastereoselective addition of phenylacetylene to racemic α-chloroketones

In this report, we have presented the first diastereoselective addition of phenylacetylene to chiral racemic chloroketones. The addition is controlled by the reactivity of the chloroketones that allowed the stereoselective reaction to be performed at -20 °C. Chiral racemic chloroketones are used in the reaction. By carefully controlling the temperature and the reaction time we were able to isolate the corresponding products in moderate yields and with good, simple and predictable facial stereoselection. Our reaction is a rare example of the use of chiral ketones in an enantioselective alkynylation reaction and opens new perspectives for the formation of chiral quaternary stereocenters.     

Multiple positive radial solutions on annuli for nonlinear Neumann problems with large growth

We consider a classical semilinear elliptic equation with Neumann boundary conditions on an annulus in R ^N . The nonlinear term is the product of a radially symmetric coefficient with a pure power. We prove that if the power is sufficiently large, the problem admits at least three distinct positive and radial solutions. In case the coefficient is constant, we show that none of the three solutions is constant. The methods are variational and are based on the study of a suitable limit problem.     

Optimal enough?

An alleged weakness of heuristic optimisation methods is the stochastic character of their solutions: instead of finding the truly optimal solution, they only provide a stochastic approximation of this optimum. In this paper we look into a particular application, portfolio optimisation. We demonstrate that the randomness of the ‘optimal’ solution obtained from the algorithm can be made so small that for all practical purposes it can be neglected. More importantly, we look at the relevance of the remaining uncertainty in the out-of-sample period. The relationship between in-sample fit and out-of-sample performance is not monotonous, but still, we observe that up to a point better solutions in-sample lead to better solutions out-of-sample. Beyond this point there is no more cause for improving the solution any further: any in-sample improvement leads out-of-sample only to financially meaningless improvements and unpredictable changes (noise) in performance.     

Generalized Cauchy difference iterative forecasting model for wind speed based on fractal time series

Nonlinear Dynamics - The local irregularity and global correlation of wind speed can be described by the fractal dimension D and the Hurst parameter H. However, the existing mathematical models...     

About the synthesis of N-1-substituted 3-aminopyrroles. A comparison

A general method for the preparation of 3-amino-1-methylpyrroles in excellent yields is reported. The key step involves the N-methylation of the nitro derivatives 2 , under phase transfer catalysis conditions.