Searle M S, Williams D H
Cambridge Centre for Molecular Recognition, University Chemical Laboratories, UK.
Nucleic Acids Res. 1993 May 11;21(9):2051-6. doi: 10.1093/nar/21.9.2051.
The thermodynamics of self-association (stacking) of free bases and nucleotides, intramolecular stacking in dinucleotides, nearest-neighbour base pair stacking interactions in duplex DNA and RNA, and the formation of hairpin loops illustrate enthalpy/entropy compensations. Large stacking exothermicities are associated with large negative entropy changes that ensure that delta G is small, permitting readily reversible associations in solution. We rationalise enthalpy/entropy compensations with reference to residual motions and torsional vibrations which make a larger entropic contribution to binding when - delta H approximately kT (thermal energy at room temperature), than when - delta H >> kT. We present a factorisation of experimental free energies for helix formation in terms of approximate contributions from the restriction of rotations, hydrophobic interactions, electrostatic interactions due to base stacking, and contributions from hydrogen bonding, and estimate the adverse free energy cost per rotor (mainly entropy) of ordering the phosphate backbone as between 1.9 and 5.4 kJ mol-1 [averaged over 12 rotors per base pair for A-U on A-U stacking (lower limit), and G-C on C-G stacking (upper limit)]. The largest cost is associated with the most exothermic stacking interactions, while the range of values is consistent with earlier conclusions from data on the fusion of hydrocarbon chains (lower value), and with entropy changes in covalent isomerisations of small molecules involving severe restrictions (upper value).
游离碱和核苷酸的自缔合（堆积）、二核苷酸中的分子内堆积、双链DNA和RNA中最近邻碱基对的堆积相互作用以及发夹环的形成，这些过程都体现了焓/熵补偿。大的堆积放热与大的负熵变相关联，这确保了吉布斯自由能变化较小，使得溶液中的缔合反应易于可逆进行。当焓变的绝对值约等于室温下的热能（-ΔH≈kT）时，相比于焓变的绝对值远大于热能（-ΔH>>kT）时，我们通过参考残余运动和扭转振动来解释焓/熵补偿，此时残余运动和扭转振动对结合的熵贡献更大。我们根据旋转受限、疏水相互作用、碱基堆积引起的静电相互作用以及氢键作用的近似贡献，对螺旋形成实验自由能进行了因式分解，并估计了磷酸骨架有序排列时每个转子的不利自由能成本（主要是熵）在1.9至5.4 kJ/mol之间[对于A-U堆积时的A-U碱基对（下限）以及C-G堆积时的G-C碱基对（上限），平均每个碱基对有12个转子]。最大的成本与放热最多的堆积相互作用相关，而该数值范围与早期关于烃链融合数据得出的结论（较低值）以及涉及严重限制的小分子共价异构化中的熵变（较高值）一致。
