Photodissociation of the water dimer: three-dimensional quantum dynamics studies on diabatic potential-energy surfaces

The results are presented of three-dimensional model studies of the photodissociation of the water dimer following excitation in the first absorption band. Diabatic potential-energy surfaces are used to investigate the photodissociation following excitation of the hydrogen bond donor molecule and of the hydrogen bond acceptor molecule. In both cases, the degrees of freedom considered are the two OH-stretch modes of the molecule being excited, and the dimer stretch vibration. The diabatic potentials are based on adiabatic potential surfaces computed with the multireference configuration-interaction method, and the dynamics of dissociation was studied using the time-dependent wave-packet method. The dynamics calculations yield a donor spectrum extending over roughly the same range of frequencies as the spectrum of the water monomer computed at the same level of theory. The acceptor spectrum has the same width as the monomer spectrum, but is shifted to the blue by 0.4-0.5 eV. The dimer spectrum obtained by averaging the donor and the acceptor spectrum is broader than the monomer spectrum, with the center of the dimer first absorption band shifted to the blue by about 0.2 eV relative to the monomer band. Our reduced dimensionality calculations do not find the red tail predicted for the dimer first absorption band by Harvey et al. [J. Chem. Phys. 109, 8747 (1998)]. This conclusion also holds if preexcitation of the dimer stretch vibration with one or two quanta is considered.     

The thermal behaviour of mixed long chain alkylammonium tetrachloromanganates(II)

The results of a calorimetric and structural investigation of mixtures of layer compounds of the kind (RNH₃)₂MCl₄, R being a long chain n-alkyl group, show that the low-temperature forms are solid solutions, mainly ordered from the conformational viewpoint, in which chains of different length are more or less randomly arranged on the surface of the anionic layers. The observed high enthalpy solid—solid phase transitions correspond to the “melting” of the hydrocarbon layers, giving solid solutions in which the conformational freedom of the alkyl chains is similar to that of hydrocarbon substances in the liquid state.     

A Novel Approach for the Synthesis of 5‐Pyridylindolizine Derivatives via 2‐(2‐Pyridyl)pyridinium Ylides

New indolizine derivatives were synthesized by an efficient one‐pot three‐component procedure starting from commercially available materials such as 2,2′‐dipyridyl, substituted bromoacetophenones, and electron‐poor alkynes in 1,2‐epoxybutane as reaction solvent and acid scavenger.     

Direct measurement by laser flash photolysis of intramolecular electron transfer in a two-domain construct of murine inducible nitric oxide synthase

Intersubunit intramolecular electron transfer (IET) from FMN to heme is essential in the delivery of electrons required for O2 activation in the heme domain and the subsequent nitric oxide (NO) synthesis by NO synthase (NOS). Previous crystal structures and functional studies primarily concerned an enzyme conformation that serves as the input state for reduction of FMN by electrons from NADPH and FAD in the reductase domain. To favor formation of the output state for the subsequent IET from FMN to heme in the oxygenase domain, a novel truncated two-domain oxyFMN construct murine inducible nitric oxide synthase (iNOS), in which only the FMN and heme domains were present, was designed and expressed. The kinetics of the IET between the FMN and heme domains in this construct was directly determined using laser flash photolysis of CO dissociation in comparative studies on partially reduced oxyFMN and single domain heme oxygenase constructs.     

Solid-phase synthesis of cyclic PNA and PNA-DNA chimeras

[structure: see text] A new and versatile on-line automated solid-phase approach to obtain cyclic PNA (I and III) and cyclic PNA-DNA chimeras (II) in highly pure form has been developed. Starting from a Tentagel matrix functionalized with a 3-chloro-4-hydroxyphenylacetic linker, the synthesis of representative, new cyclic molecules by standard peptide and phosphoramidite-based chemistry has been achieved.     

High performance liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry for sensitive determination of bioactive amines in donkey milk

In the present study we report on the optimization and validation of a sensitive high performance liquid chromatography atmospheric pressure chemical ionization mass spectrometry (HPLC–APCI–MS) method for the determination of 8 bioactive amines (histamine, tyramine, tryptamine, 2-phenylethylamine, cadaverine, putrescine, spermidine and spermine) in donkey milk samples. The method involves donkey milk pre-treatment to remove proteins and pre-column dansylation of the amines. HPLC in reversed phase mode has been used for bioactive amines separation and the operating condition of the APCI–MS system proved to be powerful and very efficient for peak assignment. The separation was accomplished in a short time with an excellent resolution for all the amine peaks. Quantification was carried out by monitoring the characteristic [M+H]⁺ ion of each amine derivative. The method sensitivity, linearity and repeatability were assayed with satisfactory results. The detection limits of the analysed amines ranged from 0.5 μg L⁻¹ to 15 μg L⁻¹; the highest LOD was for spermine. Also remarkably good recovery values were obtained; at the lowest spiking level (1 μg L⁻¹) the percent mean recoveries ranged from 77.7 to 109.7. Furthermore, as the investigations relate to a complex matrix as donkey milk, suitable studies on matrix effect were performed. Finally, the developed and validated method was applied to analyse 13 donkey milk samples. Among the identified bioactive amines, putrescine, spermine and spermidine proved to be the main amines in donkey milk. Their concentration levels in the present study were lower than the values determined in mature human, cow and sow milk.     

Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry

Interactions between kinases and small molecule inhibitors can be activation state dependent. A detailed understanding of inhibitor binding therefore requires characterizing interactions across multiple activation states. We have systematically explored the effects of ABL1 activation loop phosphorylation and PDGFR family autoinhibitory juxtamembrane domain docking on inhibitor binding affinity. For a diverse compound set, the affinity patterns correctly classify inhibitors as having type I or type II binding modes, and we show that juxtamembrane domain docking can have dramatic negative effects on inhibitor affinity. The results have allowed us to associate ligand-induced conformational changes observed in cocrystal structures with specific energetic costs. The approach we describe enables investigation of the complex relationship between kinase activation state and compound binding affinity and should facilitate strategic inhibitor design.     

Synthesis of pyrimido[1,2‐a]benzimidazol‐4(10H)‐one derivatives and evaluation of their interactions with DNA

The synthesis of new derivatives of the planar tricyclic pyrimido[1,2‐a]benzimidazole system featuring protonable side chains in the 3 and/or 10 positions is described. The reported literature procedures for the preparation of the intermediate 3‐ethoxycarbonylpyrimido[1,2‐a]benzimidazol‐4(10H)‐one 15 , starting from 2‐aminobenzimidazole 18 and diethyl ethoxymethylenemalonate, were revised. The interaction with DNA, the intrinsic binding constants, and the antiproliferative activity of a number of compounds ( 1–8, 10, 11 ) were preliminarly investigated.     

Synthesis of 2-oxazolidinones by direct palladium-catalyzed oxidative carbonylation of 2-amino-1-alkanols

[reaction: see text] 2-Oxazolidinones 2 are obtained in excellent yields (up to 100%) and with unprecedented catalytic efficiencies (up to 2000 mol of product/mol of catalyst used) by direct PdI2/KI-catalyzed oxidative carbonylation of the readily available 2-amino-1-alkanols 1. Reactions are carried out in MeOH as the solvent at 100 degrees C using a 1/6/5 CO/O2/air mixture (60 atm total pressure at 25 degrees C).