Isodesmic Model Research Articles

A proton nuclear-magnetic-resonance study of self-stacking in purine and pyrimidine nucleosides and nucleotides.

The concentration dependence of the chemical shifts of the protons H-2, H-8 and H-1' of ATP4- and of Mg(ATP)2- , of all non-labile protons of adenosine, of H-5, H-6 and H-1' of TUP, and of H-5, H-6, H-1', and H-2' of uridine have been measured. The results for the purine derivatives are consistent with the isodesmic model of indefinite non-cooperative stacking; for adenosine K = 15 +/- 2M-1, for ATP K = 1.3 +/- 0.2 M-1 and for Mg(ATP)2-K = 3.6 +/- 0.3 M-1. For the pyrimidines, uridine and TUP, stacking is much weaker and the stability constant could only be estimated; for uridine k is less than or equal to 0.5 M-1, and for UTP K approximately 0.3 M-1.

Pressure Dependence of the Selfassociation of 9‐Methylpurine in Aqueous Solution

AbstractThe selfassociation of 9‐methylpurine (9‐MP) in aqueous solution has been studied by analysis of the proton chemical shift concentration dependence at pressures up to 1500 bar. To this purpose a high pressure glass cell has been developed, fitting into the standard receiver coil of a high resolution NMR spectrometer. The influence of pressure on the UV‐spectra of 9‐MP has been measured. Pressure favours self association of 9‐MP. The thermodynamic data derived from an isodesmic association model are:K (1 bar, 20°C) = 1.4 mol−1; K (1500 bar, 20°C) = 1.8 mol−1; ΔH (van't Hoff) = ‐(9.6 ± 1)kj·mol−1 and ΔV = ‐(4.0 ± 1.0)cm3 · mol−1.

Stacking self-association of pyrimidine nucleosides and of cytosines: effects of methylation and thiolation

Stacking self-association equilibria in aqueous solutions of m3uridine, m34,2',3',5'uridine, 2'-deoxyuridine, m13,4,4cytosine, m14,4,4,5cytosine, s2cytidine and s4thymidine were studied at various temperatures by vapour-pressure osmometry. Equilibrium constants Kst's were computed on the assumption of the isodesmic model of self-association. Enthalpies of association were also obtained from the temperature dependence of Kst according to the van't Hoff equation. Analysis of the equilibrium and thermodynamic parameters demonstrated involvement of hydrophobic interactions in the stabilization of complexes of tetramethyluridine. Dipole-induced dipole interactions seem to predominate in the formation of s2C, s4T and of both dimethylaminocytosine complexes.

Osmometric studies on self-association of pyrimidines in aqueous solutions: evidence for involvement of hydrophobic interactions.

Vapour pressure osmometric studies were performed on stacking self-association of 25 uracil derivatives variously C- and N-substituted with polar and alkyl groups in aqueous solution at various temperatures. The respective equilibrium association constants Kst were computed on the assumption of the isodesmic model of self-association (K2=K3=...=Kn=Kst). Enthalpies of association for most of the compounds studied were obtained from the temperature-dependence of Kst, according to the van 't Hoff equation. Analysis of the equilibrium and thermodynamic parameters in terms of the association mechanism demonstrated the involvement of classical hydrophobic interactiors in the stabilization of complexes of di-and higher alkylated uracils. Data for the derivatives substituted with polar groups proved consistent with the predominant involvement of dipole-induced dipole forces in the association.

The self-association of adenosine-5'-triphosphate studied by circular dichroism at low ionic strengths

The self-association of adenosine-5'-triphosphate (ATP) was Studied as a function of pH, additional counterions, concentration and temperature. Circular dichroism measurements were employed as a measure of the base-stacking. The self-association of ATP is pH dependent with the protonation of the adenine ring helping stabilize the association. Highly charged counterions alter this aggregation. At pH 2.8 and 20° C, a dimerization constant of 88 M −1 is obtained, white an isodesmic model leads to an equilibrium constant of 158 M −1. With increasing pH, the association constants decrease. At pH 2.8 there is a very strong temperature dependence of the CD amplitude. These results indicate the existence of additional electrostatic stabilization for the stacking of the adenine rings. At acidic pHs, models are proposed to explain this high degree of stability and a calculation of the approximate electrostatic contribution to the aggregation shows it to be of the proper magnitude.

Stacking interactions of nucleobases: NMR-investigations. I. Self association of N6, N9-dimethyladenine and N6-dimethyl-N9-ethyladenine.

The selfassociation of N6,N9-dimethyladenine and N6-dimethyl-N9-ethyladenine has been studied by means of NMR technique. The thermodynamic quantities have been calculated using an isodesmic NMR model with three NMR parameters (the monomer shift deltaM and two complex shifts delta2 and delta3). The dependence of the thermodynamic quantities on the NMR parameters is discussed. Special attention is given to the determination of deltaM and its temperature dependence. Calculations with delta3 = 2 - delta2 and deltaM taken independently of temperature result in an average entropy deltaS = - 17.9 +/- 1.8 e.u. for N6,N9-dimethyladenine and deltaS = - 16.7 +/- 1.7 e.u. for N6-dimethyl-N9-ethyladenine and in an average enthalpy deltaH = - 7.2 +/- 0.6 kcal - mol-1 for both substances investigated.

Stacking interactions of nucleobases: NMR-investigations. II. Self-association of purine-and pyrimidine-derivatives.

The self-association of various purine- and pyrimidine-derivatives in D2O has been studied by means of NMR technique. The thermodynamic quantities have been calculated using an isodesmic NMR model. Among the nucleobases investigated, the adenine-derivatives were found to be most suitable for quantitative determination. A comparison of methylated adenine-derivatives and the pH-dependence of the self-association lead to the conlcusion, that the stacking associates are stabilized by special van der Waals interactions based, essentially, on the polarizability of the pi-electron-system of the assciated molecules.

Studies of intermolecular interactions of nucleic acid bases in aqueous solutions by the proton magnetic resonance method: Self-association of 6,9-dimethyladenine and its pyrazole analogue and their association with methyl-substituted cytosine and uracil

To study intermolecular interaction the concentration and temperature dependence of chemical shifts of the protons of 6,9-dimethyladenine (I), its pyrazole analogue I-methylaminopyrazolo-3,4-d pyrimidine (II), as well as 1,4-dimethylcytosine and dimethyl derivatives of uracil, modelling the main and rare tautomeric forms of uracil: 1,3-; 1,4-; 2,4-dimethyluracils, both separately and in mixtures have been investigated. A conclusion has been made about homoassociation in solutions of I and II as well as heteroassociation of I and II with pyrimidine derivatives into complexes, having the stacked structure. From the differences in values of the chemical shifts, which are dependent on concentration, for the protons of six-membered and five-membered cycles the authors came to conclusions about the conformation in the homoassociates of I and II. Association of studied compounds is not limited to the dimer formation, but is well described by the isodesmic model. Thermodynamic characteristics of association have been obtained and discussed. A correlation between equilibrium association constants and component polarizability has been revealed. Taking homoassociation of I and heteroassociation of I with IV as examples, it has been established, that in 2H 2O stacking interaction of cation with cation and cation with neutral molecule is considerably weaker than the interaction between neutral molecules.

Thermodynamics and kinetics of base-stacking interactions.

The thermodynamics and kinetics of the self‐association of N6, N9‐dimethyladenine has been studied as a model system for base stacking. Molal osmotic coefficients have been determined by vapor pressure osmometry in aqueous solutions at four different temperatures. These data, indicating a very high degree of association much beyond the dimer stage, are consistent with a series of consecutive equivalent association processes. The analysis is performed with an isodesmic model, which allows for cooperativity of the first binding step. Cooperativity can almost be neglected in the present case; the thermodynamic parameters for the formation of stacks are ΔH°=– 8.7 (° 1.5) kcal/mol and ΔS°=– 21.6 cal/K resulting in a stability constant K= 60 at 20°C.The kinetics of base stacking has been investigated by means of sound absorption techniques in the 10–100 MHz frequency range. The excess absorption profiles are only slightly broader than theoretically expected for a single relaxation process. The data can be explained by an isodesmic kinetic model. Formation of stacks proceeds with a rate constant of about 109 M−1 sec−1 and an activation enthalpy of + 6 kcal/mol. Evaluation of the amplitudes leads to a volume change of 6.8 ml (at 25°C) per mol of stacking sites. The volume change decreases with increasing temperature. Optical measurements in a pressure cell show that the volume decreases with increasing number of stacks.These results are discussed with respect to current theories of base stacking. Both ΔH and ΔV found for the stacking equilibrium are in contrast to the thermodynamic parameters of hydro‐phobic interactions according to the standard view. The present data demonstrate a characteristic difference of hydrophobic interactions between unpolar, unpolarisable particles like simple hydrocarbons and between compounds like nucleic acid bases with high polarisability and a dipole structure.