Effect of gem-Difluorination on the Key Physicochemical Properties Relevant to Medicinal Chemistry: The Case of Functionalized Cycloalkanes

Physico-chemical properties important to drug discovery (pK_a, LogP, and aqueous solubility), as well as metabolic stability, were studied for a series of functionalized gem-difluorinated cycloalkanes and compared to those of non-fluorinated and acyclic counterparts to evaluate the impact of the fluorination. It was found that the influence of the CF₂ moiety on the acidity/basicity of the corresponding carboxylic acids and amines was defined by inductive the effect of the fluorine atoms and was nearly the same for acyclic and cyclic aliphatic compounds. Lipophilicity and aqueous solubility followed more complex trends and were affected by the position of the fluorine atoms, ring size, and even the nature of the functional group present; also, significant differences were found for the acyclic and cyclic series. Also, gem-difluorination either did not affect or slightly improved the metabolic stability of the corresponding model derivatives. The presented results can be used as a guide for rational drug design employing fluorine and establish the first chapter in a catalog of the key in vitro properties of fluorinated cycloalkanes.     

Recent advances in (hetero)cyclizations of N-vinylazoles (microreview)

Chemistry of Heterocyclic Compounds - Recent advances in chemistry of N-vinylazoles are surveyed in this microreview, including results published in the last decade. In particular, reactions...     

Reactivity of [Ge9{Si(SiMe3)3}3]− Towards Transition‐Metal M2+ Cations: Coordination and Redox Chemistry

Recently the metalloid cluster compound [Ge₉Hyp₃]^? ( 1 ; Hyp=Si(SiMe₃)₃) was oxidatively coupled by an iron(II) salt to give the largest metalloid Group 14 cluster [Ge₁₈Hyp₆]. Such redox chemistry is also possible with different transition metal (TM) salts TM²⁺ (TM=Fe, Co, Ni) to give the TM⁺ complexes [Fe(dppe)₂][Ge₉Hyp₃] ( 3 ; dppe=1,2‐bis(diphenylphosphino)ethane), [Co(dppe)₂][Ge₉Hyp₃] ( 4 ), [Ni(dppe)(Ge₉Hyp₃)] ( 5 ) and [Ni(dppe)₂(Ge₉Hyp₃)]⁺ ( 6 ). Such a redox reaction does not proceed for Mn, for which a salt metathesis gives the first open shell [Hyp₃Ge₉‐M‐Ge₉Hyp₃] cluster ( 2 ; M=Mn). The bonding of the transition metal atom to 1 is also possible for Ni (e.g., compound 6 ), in which one or even two nickel atoms can bind to 1 . In contrast to this in case of the Fe and Co compounds 3 and 4 , respectively, the transition‐metal atom is not bound to the Ge₉ core of 1 . The synthesis and the experimentally determined structures of 2 – 6 are presented. Additionally the bonding within 2 – 6 is analyzed and discussed with the aid of EPR measurements and quantum chemical calculations.     

The catalytic efficiency of Fe-containing nanocomposites based on highly dispersed silica in the reaction of CO2 hydrogenation

Research on Chemical Intermediates - Oxide Ni(80)Fe(20)/SiO2, Co(93)Fe(7)/SiO2, and Ni(19)Co(77)Fe(4)/SiO2 nanocomposites (NCs) were prepared using highly dispersed silica. It was modified by...     

Structure of salted and discharged globules of hydrophobic polyelectrolytes adsorbed from aqueous solutions

In this article, we compare structures of protonated poly(2-vinylpyridine) globules (2D compact coils on the surface) adsorbed on the mica surface from aqueous solution when the shrinking is brought about either by discharging the molecules at an elevated pH or by adding monovalent and polyvalent salts. We study the structure of the PE coils using in situ atomic force microscopy experiments in aqueous solutions in a liquid cell. The abrupt coil-to-globule transition caused by pH changes and the discharge of polymer chains resulted in compact globules. If the pH corresponding to extended coil conformation remains unchanged, the coil shrinks due to the added salt. The size of the globule in the latter case corresponds to the unperturbed dimension of the polymer coil. There is no essential difference in the dimensions of the globules as obtained in the presence of monovalent and multivalent counterions for the studied ionic strength. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1623–1627, 2010     

Chemometrics-assisted spectrophotometric method for simultaneous determination of vitamins in complex mixtures

An advanced independent component analysis algorithm (MILCA) is applied for simultaneous chemometric determination of fat- and water-soluble vitamins in complex mixtures. The analysis is based on the decomposition of spectra of multicomponent mixtures in the UV region. The key features of the proposed method are simplicity, accuracy, and reliability. Comparisons between the new algorithm and other established methods (MCR-ALS, SIMPLISMA, other ICA techniques) were made. Our results indicate that in most cases, MILCA is comparable or even outperforms other chemometrics methods taken for comparisons. The influence of different factors (abundance of components, noise, step of spectral scan, and scan speed) on decomposition performance has been investigated. The optimal conditions for spectroscopic registration have been identified. The proposed method was used for analysis of model mixtures and real objects (multivitamin drugs, food additives, and energy drinks). The resolved concentrations match well with the declared amounts and the results of reference methods.     

Rational modulation of the periodicity in linear hydrogen-bonded assemblies of trimesic acid on surfaces

We demonstrate a surprising cooperative adsorption process at the liquid-solid interface, involving self-assembly in which a three-fold hydrogen-bonding unit (trimesic acid, TMA) is forced into a linear pattern by noncovalent interaction with an alcohol. Our work shows that the unexpected linear pattern formed by coadsorption of TMA and alcohols can be modulated in size by choosing alcohols with different chain lengths.     

The Lamperti correspondence extended to Lévy processes and semi-stable Markov processes in locally compact groups

We establish Lamperti representations for semi-stable Markov processes in locally compact groups. We also study the particular cases of processes with values in R$\mathbb{R}$ and C$\mathbb{C}$ under the hypothesis that they do not visit 0. These Lamperti representations yield some properties of these semi-stable Markov processes.