Kazimierz L. Wierzchowski

Dipole moments of 2,4-diketopyrimidines: Part II: Uracil, thymine and their derivatives

Abstract The dipole moments of uracil, thymine and of 29 of their variously substituted derivatives were experimentally determined in dioxane. A vector scheme of calculations was applied to evaluate the effects of alkyl and halogen substituents on the dipole moment of uracil. The dipole moments of a number of diketopyrimidines studied were also calculated quantum mechanically by the CNDO 2 method. General agreement between the experimental and calculated values was obtained. The substituent-induced electron charge redistributions are discussed in terms of σ- and τ-populations.

Thermochemistry of aqueous solutions of alkylated nucleic acid bases. III. Enthalpies of hydration of uracil, thymine and their derivatives.

Enthalpies of sublimation DeltaH(0)(subl) crystalline uracil, thymine and their methylated derivatives as well as of N,N-diethylthymine were determinated by the quartz-resonator method and mass spectrometry. Enthalpies of solution at infinite dilution DeltaH(0)(sol) in water of aBcylated compounds were obtained calorimetrically. Hence the calculated enthalpies of hydration: DeltaH(0)(hydrsubal) = DeltaH(0)(sol) - DeltaH(0)(subl), were corrected for energies of cavity formation in pure liquid water to yield enthalpies of interaction DeltaH(0)(sint) of the solutes with their hydration shells. For uracil DeltaH(0)(int) = -59.8 kJ mole(-1) was obtained in this way. This value decreased linearly on N-methyl substitution with a mean increment of about 6.5 kJ mole CH2(-1). After C(5) or C(6) ring substitution it increased by about 3 kJ. These results are discussed in connection with heat of dilution data and theoretical schemes of hydration.

Intramolecular Electron Transfer in Peptides Containing Methionine, Tryptophan and Tyrosine: A Pulse Radiolysis Study

The kinetics of pulse radiolytically induced intramolecular radical transformations: Trp/N.----Tyr/O., Tyr/O.----Trp/N., Met/S therefore Br----Trp/N. and Met/S therefore Br----Tyr/O. has been investigated at various pH levels and temperatures in model peptides: Trp-(Pro)n-Tyr, Trp-(Gly)n-Tyr, Trp-(Pro)n-Met (n = 0-3), Tyr-Phe-Met-Arg-Phe-NH2 x 2AcOH, Met5-enkephaline and [D-Ala]2Met5-enkephaline. The rate constants of the Trp/N.----Tyr/O. transformation at pH 8 were found to decrease exponentially with the distance between Trp and Tyr in the proline peptides, while in the glycine peptides the rate of the transformation is less dependent on the number of bridging glycine residues. The activation energies determined fall into the range 10-20 kJ mol-1 irrespective of: (i) the ionization state of tryptophyl radical and tyrosine, (ii) type of bridging amino acids, and (iii) reversal of the direction of the electron transfer upon tyrosine OH group ionization. The activation entropies at 298 K for the peptides of the glycine and proline series are negative and rather high, and fall into the relatively narrow range of -90 to -140 J mol-1 deg-1. These activation parameters seem to indicate that a tunnelling mechanism is involved in the electron transfer between strictly oriented aromatic moieties of Trp and Tyr. The variation of the activation parameters with average separation distance in the case of Trp-(Pro)n-Tyr shows a predominance of the electronic factor over the nuclear in determining the distance dependence of the electron transfer rate. The intramolecular Met/S therefore Br----Tyr/O. transfer proceeds with the rate constant of 1.1 x 10(5) s-1 in Met5-enkephaline and 5.7 x 10(4) s-1 in [D-Ala]2Met5-enkephaline. The activation parameters for this transformation Ea = 30 kJ mol-1 and delta S298 = -62 J mol-1 deg-1 are close to those of the Trp/N.----Tyr/O. transformation, suggesting a similar mechanism for the electron transfer.

Barrier to rotation and conformation of the -NR2 group in cytosine and its derivatives. Part II. Experimental and theoretical dipole moments of methylated cytosines☆

The dipole moments of several cytosine, methylaminocytosine and dime-thylaminocytosine derivatives with and without an ortho methyl group were determined experimentally in dioxane and benzene. Calculations of total energies and dipole moments were performed by the CNDO/2 and INDO methods for sp2 and sp3 hybridization of exocyclic nitrogen for different values of rotational angle phiC-N. Comparison of the experimental dipole moments with those calculated for the energy minima suggests that the conformation of the dimethylamino group is not planar and differs from that found in cytosine. 1,5,7-Trimethylcytosine, with the dipole moment of 7 Deby units, was considered to be the model compound which closely reproduces the dipole moment of cytosine.

Thermochemistry of aqueous solutions of alkylated nucleic acid bases. I. Apparent molar heat capacities of uracil, thymine and their derivatives.

Apparent molar heat capacities phiC(p(1,3)) of uracil, thymine and a series of their alkylated derivatives: m(1)Ura,m(1,3)(2) Ura, m(1,3)(2)Thy, mi(1,3,6)(3)Ura, m(1,3)(2),e(5)Ura and e(1,3)(2)Thy in dilute aqueous solutions were measured in the temperature range of 293.15-388.15 K, using a differential adiabatic scanning microcalorimeter. They were found to lie (i) much higher than the estimated heat capacities C(p)(s) of solid compounds, (ii) comparable with the respective partial molar heat capacities at infinite dilution, C(o)(p2), and (iii) linearly related to the number nH of hydrogen atoms covalenuy bound to the solute molecules. The increment thus obtained DeltaC(o)(p2)=42.8 J mole(-1) K(-1)n(-1)(H) per each hydrogen atom at 298.15 K proved (i) to coincide closely with those found previously for homologous series of aliphatic amides and hydrocarbons, and (ii) to decrease with a rise of temperature. These findings imply the involvement of hydrophobic hydration of the solutes.

Thermochemistry of aqueous solutions of alkylated nucleic acid bases: IV. Enthalpies of hydration of 5-alkyluracils

Enthalpies of sublimation, DeltaH degrees (subl) and of solution in water, DeltaH degrees (sol) were determined for a series of crystalline 1,3-dimethyl-uracil derivatives substituted at the C5-ring carbon atom with alkyl groups (-C(n)H(2n+1), n = 2-4) and some of their C(5.6)-cyclooligomethylene analogues (-(CH2)(n)-, n = 3-5). From these data. enthalpies of hydration DeltaH degrees (hydr)= DeltaH degrees (sol) - DeltaH degrees (subl) were calculated and corrected for energies of cavity formation in pure liquid water in order to obtain enthalpies of interaction, DeltaH degrees (int) of the solutes with their hydration shells. The latter are discussed together with the recalculated DeltaH degrees (int) for variously methylated uracils, obtained previously according to a simplified correction procedure, in terms of perturbations in the energy and scheme of hydration of the diketopyrimidine ring brought about by alkyl substitution. It was found that each -CH2-group added with an alkyl substitution contributes favorably about -20 kJ mol(-1) toDeltaH degrees (int). This contribution is partially cancelled by the unfavorable contribution to DeltaH degrees (int) connected with removal of some water molecules bound in the first and subsequent hydration layers by an alkyl substituent. This is particularly evident on substitution at the polar side of the diketopyrimidine ring on which water molecules are expected to be bound specifically.

Pulse Radiolysis Studies of Intramolecular Electron Transfer in Model Peptides and Proteins. IV. Met/S∴Br→Tyr/O· Radical Transformation in Aqueous Solution of H-Tyr-(Pro)n-Met-OH Peptides

The intramolecular radical transformation Met/S:.Br-->Tyr/O. in aqueous peptides H-Tyr-(Pro)n-Met-OH, n = 0-3, was investigated in the temperature range of 283-328 K by pulse radiolysis. Corresponding first-order rate constants and thermodynamic parameters of activation of electron transfer, Ea and delta S++, were determined from kinetic data. The rate constants of the reaction were found to decrease exponentially with the number of Pro units and the distance between CR atoms of the terminal amino acids, with a correlation coefficient alpha = 3.2 +/- 0.5 nm-1 at 298 K. Its value appeared to be temperature dependent suggesting the occurrence of thermally induced conformational changes in the peptides. Analysis of experimental data in terms of known conformational properties of the peptides indicates that apparent values of alpha, Ea and delta S++ are probably complicated functions of conformation and thermodynamic stability of the oligoproline bridge, varying with the number of Pro residues, and of intramolecular hydrophobic interactions between side chains of tyrosine and methionine. Estimation of the relative efficiency of electron transfer pathways through the peptide backbone and through direct and/or water mediated contact between groups bearing radical sites led to the conclusion that partitioning of electron transfer along these pathways is likely to occur.

Thermochemistry of aqueous solutions of alkylated nucleic acid bases: II. Apparent molar relative enthalpies of dilution of solutions containing uracil and thymine derivatives

Apparent molar relative enthalpies of dilution phi(L)of aqueous solutions of a series of alkylated diketopyrimidines: m(1)Ura, m(1,3)(2)Ura, m(1,3)(2)Thy, m(1,3,6)(3)Ura and e(1,3)(2)Thy were measured as a function of concentration of the solutes at three temperatures 298.15, 308.15 and 318.15 K. Dilution proved to be an endothermic process over the whole range of molalities m and temperatures studied for all compounds except the e(1,3)(2)Thy solution, the dilution of which, with the exception of the lowest concentrations (m > 0.2-0.3) was an exothermic process. Partial molar relative enthalpies of dilution -L(2)(m) derived from phi(L)(m) functions were analysed as if they were composed of two additive contributions: an endothermic one -L(2), (m(1)) and an exothermic one 1.2, (m(as)0), owing to the presence in the solutions of a free monomer m(1) or associated species m(as), respectively. Partial molar heat capacities of the solutes, evaluated by differentiation of -L(2)(m) functions in respect to temperature, decreased with the rise of concentration in the order of the tendency of the solutes to stacking association. Changes in heat content and in heat capacity of solutions upon their dilution are interpreted in terms of involvement of hydrophobic hydration and association of the solutes.

Apparent molar heat capacities and volumes, van der Waals volumes and accessible surface areas of alkylated derivatives of cytosine and uracil in aqueous solutions at 25°C.

Densities and specific heat capacities of aqueous solutions: 1,3,5,6-tetramethyluracil, 1,6-dimethyl-3-ethyluracil, 1,6-dimethyl-3-propyluracil, 1,6-dimethyl-3-butyluracil, 1,N4-trimethylcytosine, 1,N4-dimethyl-5-ethylcytosine, 1,N4 dimethyl-5-propylcytosine, 1,N4-dimethyl-5-butylcytosine were determined using flow calorimetry and flow densimetry at 25°C. Apparent molar volumes and heat capacities, van der Waals volumes and accessible surface areas were determined. It was stated that for alkylcytosines and alkyluracils partial molar volumes and heat capacities correlate linearly with the number of substituted methylene groups-CH2-as well as with the van der Waals volumes and accessible surface areas of the compounds studied; for cyclooligouracils the cyclization effect was discussed.

Thermochemistry of aqueous solutions of alkylated nucleic acid bases. VIII: Enthalpies of hydration of 6-alkyluracils

Enthalpies of solution in water ΔHsolo and enthalpies of sublimation ΔHsubo were determined for a number of crystalline derivatives of uracil: 1,6-dimethyluracil (m21,6Ura), 1,3,6-trimethyluracil (m31,3,6Ura), 6-ethyl-1,3-dimethyluracil (e6m21,3Ura), 6-propyl-1,3-dimethyluracil (pr6m21,3Ura) and 6-butyl-1,3-dimethyluracil (but6m21,3Ura). Standard enthalpies of hydration ΔHhydro and standard enthalpies of interaction ΔHinto of the solutes with their hydration shells were calculated. The data obtained show that dependence of ΔHinto on the number of-CH2- groups of n-alkyl chain added upon substitution of diketopyrimidine ring is nonlinear. This finding is discussed in connection with results of X-ray diffraction structure determinations for the crystalline compounds.