Chimeric platinum-polyamines and DNA binding. Kinetics of DNA interstrand cross-link formation by dinuclear platinum complexes with polyamine linkers

The first observation of a polyamine-DNA interaction using 2D [(1)H, (15)N] HSQC NMR spectroscopy allows study of the role of the linker in polynuclear platinum-DNA interactions and a novel "anchoring" of the polyamine by Pt-DNA bond formation allows examination of the details of conformational B → Z transitions induced by the polyamine. The kinetics and mechanism of the stepwise formation of 5'-5' 1,4-GG interstrand cross-links (IXLs) by fully (15)N-labeled [{trans-PtCl((15)NH(3))(2)}(2){μ-((15)NH(2)(CH(2))(6)(15)NH(2)(CH(2))(6)(15)NH(2))}](3+) (1,1/t,t-6,6, 1) and [{trans-PtCl((15)NH(3))(2)}(2){μ-((15)NH(2)(CH(2))(6)(15)NH(2)(CH(2))(2)(15)NH(2)(CH(2))(6)(15)NH(2))}](4+) (1,1/t,t-6,2,6, 1') with the self-complementary oligonucleotide 5'-{d(ATATGTACATAT)(2)} (duplex I) are compared to the analogous reaction with 1,0,1/t,t,t (BBR3464) under identical conditions (pH 5.4, 298 K). Initial electrostatic interactions with the DNA are delocalized and followed by aquation to form the monoaqua monochloro species. The rate constant for monofunctional adduct formation, k(MF), for 1 (0.87 M(-1) s(-1)) is 3.5 fold higher than for 1,0,1/t,t,t (0.25 M(-1) s(-1); the value could not be calculated for 1' due to peak overlap). The evidence suggests that several conformers of the bifunctional adduct form, whereas for 1,0,1/t,t,t only two discrete conformers were observed. The combined effect of the conformers observed for 1 and 1' may play a crucial role in the increased potency of these novel complexes compared to 1,0,1/t,t,t. Treated as a single final product, the rate of formation of the 5'-5' 1,4-GG IXL, k(CH), for 1 (k(CH) = 4.37 × 10(-5) s(-1)) is similar to that of 1,0,1/t,t,t, whereas the value for 1' is marginally higher (k(CH) = 5.4 × 10(-5) s(-1)).     

Development of an HPLC Method for Determination of Related Impurities in Prilocaine Substance

Development of a reversed phase high performance liquid chromatographic method for determination of six related impurities in prilocaine substance is reported. The test of related impurities in European Pharmacopoeia (Ph. Eur.) cannot meet the demands with the chromatographic parameters given, therefore different types of chromatographic systems and eight columns have been evaluated in the present study. A new method with a Hypercarb column was developed and validated. This method fulfils the demands in the Ph. Eur., and the validation shows that the method is selective, reproducible, linear, accurate and robust with sufficient limits of detection (0.001–0.004% of 2.5?mg prilocaine mL^?1) and quantification (0.002–0.009% of 2.5?mg prilocaine mL^?1).     

Polarised vibrational spectra of KH2PO3 single crystal

Polarised IR and Raman spectra for KH₂PO₃ single crystal samples were measured at room temperature. Additionally, the IR spectra for the Xb(Z) sample were also measured at low temperatures (300–14 K). The spectra are discussed on the basis of oriented gas model and group theory. The stretching νOH vibrations of the hydrogen bonds with the OO distances of 2.547 and 2.529 Å give characteristic broad ABC-type bands in the IR (polarised parallel to the X and to the b(Z) directions) and Raman (xx, xz and yx) spectra. The Davydov-type (correlation field or factor group) splitting is not observed for the νOH modes. The presence of two independent hydrogen bonds in the crystal is manifested by splitting of the C band into two (C′, C″) components and by the different frequencies of the out-of-plane bending γOH vibrations. The in-plane bending modes δOH are strongly mixed/coupled with the stretching vibrations of the PO₃ groups.

The C bands (C′ and C″) change into quite sharp bands on lowering of the temperature. Various simplified models for internal vibrations of the phosphite anions are applied for finding a correlation between the crystal structure and polarised vibrational spectra. The stretching vibrations of the νPH groups manifest their unequivalence in two symmetry-independent hydrogenphosphite anions.     

Theory of profiles of hydrogen stretching infrared bands of hydrogen-bonded solids. Multi-Fermi resonance effects and strong coupling between the high-frequency hydrogen stretching vibration and low-frequency phonons

A theory is developed to describe the profiles of hydrogen stretching infrared bands of hydrogen-bonded solids taking into account the anharmonic coupling between the high-frequency stretching vibration, ν(XH), and low-frequency lattice phonons, Ω_i, as well as multi-Fermi resonances between states involving the ν(XH) stretching and overtones or combinations of some internal modes. The theory has been constructed in the framework of the extended molecular exciton Davydov approach. Model calculations show that the strong couplings between the high frequency ν(XH) and low-lattice vibration frequencies, Ω_i, generate the broadness of the ν(XH) band but the multi-Fermi resonances between the ν(XH) state and overtones or combinations of internal modes generate the complicated substructure band which is observed experimentally.     

CNDO/2 molecular orbital calculations of the hemi-Dewar and valene structures of naphthalene

CNDO/2 molecular orbital calculations have been carried out on the hemi-Dewar and valene structures of naphthalene in order to determine the configuration of minimum energy.     

Carpet Beater Molecules: Synthesis and Characterization of Functional Hexa-peri-benzocoronene–Alkyne Coupling Products

Within the scope of this paper, nine π-expanded mono-substituted 5,8,11,14,17-pentakis-(tert-butyl)-hexa-peri-hexabenzocoronenes (HBC) are introduced. 2-Iodo-5,8,11,14,17-pentakis-(tert-butyl)-hexa-peri-hexabenzocoronene served as precursor and was reacted with ethynyltrimethylsilane in a Sonogashira coupling reaction. The acetylene unit is used as a linker and can undergo another Sonogashira coupling reaction combining different phenyl coupling partners with the HBC core. The electron-withdrawing groups such as nitrile, pyridine and carbonyl species (aldehyde, methylester, carboxylic acid) as well as the three quinoxaline based species (diphenylquinoxaline, dibenzo[a,c]phenazine, phenanthro[4’,5’-a,b,c]phenazine) serve as substitution moieties. Their influence on the optoelectronic properties were investigated by UV/Vis absorption spectroscopy demonstrating a maximum redshift of 7 nm compared to starting compound 2-Iodo-5,8,11,14,17-pentakis-(tert-butyl) HBC. As for the phenanthro[4’,5’-a,b,c]phenazine substituted HBC a dramatic decrease in the intensity of the absorption of the UV/Vis spectrum was observed. The fluorescence spectroscopy pointed out that the dibenzo[a,c]phenazine and phenanthro[4’,5’-a,b,c]phenazine substitution changed the spectra to one broad peak departing from the characteristic HBC-like emission pattern.     

Effect of temperature on the luminescence processes of SrAl2O4:Eu

The UV excited and persistent luminescence properties as well as thermoluminescence (TL) of Eu²⁺ doped strontium aluminates, SrAl₂O₄:Eu²⁺ were studied at different temperatures. Two luminescence bands peaking at 445 and 520 nm were observed at 20 K but only the latter at 295 K. Both Sr-sites in the lattice are thus occupied by Eu²⁺ but at room temperature efficient energy transfer occurs between the two sites. The UV excited and persistent luminescence spectra were similar at 295 K but the excitation spectra were different. Thus the luminescent centre is the same in both phenomena but excitation processes are different. Two TL peaks were observed between 50 and 250 °C in the glow curve. Multiple traps were, however, observed by preheating and initial rise methods. With longer delay times only the high temperature TL peak was observed. The persistent luminescence is mainly due to slow fading of the low temperature TL peak but the step-wise feeding process from high temperature traps is also probable.     

The time arrow in a Planck gas

In this paper the quantum heat transport equation (QHT) is applied to the study of thermal properties of Planck gas, i.e., a gas of massive particles with mass equal to the Planck massM _P = (łc/G)^1/2 and whose relaxation time equals the Planck timeτ _p = (łG/c ⁵)^1/2. The quantum of thermal energy for a Planck gas,E ^Planck = 10¹⁹GeV, and the quantum thermal diffusion coefficientD ^Planck = (ħG/c)^1/2 are calculated. Within the framework of QHT the thermal phenomena in a Planck gas can be divided into two classes: for a time period shorter thanτ _p , the time reversal symmetry holds and for a time period longer thanτ _p , time symmetry is broken, i.e., a time arrow is created.     

Vibrational spectra and stereochemistry of mono- and polysaccharides

A comparative study of the IR and Raman spectra of D-glucose anomers is reported. The spectra were found to differ between the anomers, despite the absence of symmetry elements in the anomer molecules. The results of theoretical calculations are systematized; it was found that the skeletal CiOi or CiO(i+1) (i=1, 2, 3, 4, 5) bond is characterized by a specific set of frequencies of normal vibrations, which have predominant contributions from the vibrations of atomic groups involving these bonds to the potential energy distribution (PED). The frequencies of normal vibrations with the major contribution to PED from CO and CC bonds are well separated and differ between the D-glucose anomers. The C5C6 bond has the greatest number of normal vibrations with predominant contributions to PED. Model calculations of vibrational spectra are reported for D-glucose anomers with modified (β→α and α→β) conformations of the CH₂OH group. B. I. Stepanov Institute of Physics, Belarus Academy of Sciences. Institute of Low Temperatures and Structural Studies, Polish Academy of Sciences, Wroclaw. Translated fromZhurnal Strukturnoi Khimii, Vol. 36, No. 2, pp. 322–329, March–April, 1995. Translated by L. Smolina