The binding interaction of a prospective anti-cancer photosensitizer, norharmane (NHM, 9H-pyrido[3,4-b]indole) with double stranded RNA reveals a primarily intercalative mode of binding. Steady-state and time-resolved fluorescence spectroscopic results demonstrate the occurrence of drug-RNA binding interaction as manifested through environment-sensitive prototropic equilibrium of NHM. However, the key finding of the present study lies in unraveling the complexities in the NHM-RNA binding thermodynamics. Isothermal Titration Calorimetry (ITC) results reveal the presence of two thermodynamically different binding modes for NHM. An extensive temperature-dependence investigation shows that the formation of Complex I is enthalpically (ΔH_I < 0) as well as entropically (TΔS_I > 0) favored with the enthalpic (entropic) contribution being increasingly predominant in the higher (lower) temperature regime. On the contrary, the formation of Complex II reveals a predominantly enthalpy-driven signature (ΔH_I < 0) along with unfavorable entropy change (TΔS_I < 0) with gradually decreasing enthalpic contribution with temperature. Such differential dependences of ΔH_I and ΔH_II on temperature subsequently lead to opposing heat capacity changes underlying the formation of Complex I and II (${\mathrm{\Delta }C}_p^I<0and{\mathrm{\Delta }C}_p^{\mathit{II}}>0$). A negative ΔC_p underpins the pivotal role of ‘hydrophobic effect’ (release of ordered water molecules) for the formation of Complex I, while a positive ΔC_p marks the thermodynamic hallmark for ‘hydrophobic hydration’ (solvation of hydrophobic (or nonpolar) molecular surfaces in aqueous medium) for formation of Complex II. A detailed investigation of the effect of ionic strength enables a component analysis of the total free energy change (ΔG).

前瞻性抗癌光敏剂正畸烷（NHM，9 H-吡啶并[3,4- b ]吲哚）与双链RNA的结合相互作用揭示了结合的主要插入模式。稳态和时间分辨荧光光谱结果证明了药物-RNA结合相互作用的发生，这是通过NHM对环境敏感的质子平衡所证明的。然而，本研究的关键发现在于揭示NHM-RNA结合热力学的复杂性。等温滴定量热法（ITC）结果揭示了NHM存在两种热力学上不同的结合模式。一个广泛的温度依赖性调查表明，复合物I的形成焓（ΔH_我 <0）以及熵（TΔS_我 > 0）与所述焓（熵）贡献是在较高（较低）的温度状况越来越占优势的青睐。与此相反，复合物II的形成揭示了一个主要焓驱动的签名（ΔH_我 与不利的熵变（TΔS沿<0）_我 <0）与逐渐减小与温度焓贡献。ΔH的这种不同的依赖性_我和ΔH _II温度随后导致相对复杂I和II的形成底层的热容量变化（${\mathrm{\Delta }C}_p^{\mathrm{一世}}<0\mathrm{一个}ñd{\mathrm{\Delta }C}_p^{\mathit{II}}>0$）。负ΔC _p支撑着的“疏水性效应”（有序水分子的释放）为复合物I的形成中的关键作用，而正ΔC _p标记为“疏水水合”的（溶剂化热力学标志疏水性（或极性）分子在水介质中的表面）形成配合物Ⅱ。对离子强度影响的详细研究使得能够对总自由能变化（ΔG）进行成分分析。