Supramolecular 尾-Cyclodextrin Adducts of Boron-Rich DNA Metallointercalators Containing Dicarba-closo-dodecaborane(12)
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- 作者：H. Y. Vincent Ching ; Ronald J. Clarke ; Louis M. Rendina
- 刊名：Inorganic Chemistry
- 出版年：2013
- 出版时间：September 16, 2013
- 年：2013
- 卷：52
- 期：18
- 页码：10356-10367
- 全文大小：548K
- 年卷期：v.52,no.18(September 16, 2013)
- ISSN：1520-510X
文摘
A chiral, isomeric series of novel boron-rich PtII metallointercalators ([PtL2(phen)](NO3)2: L = (x)-(1,y-closo-carboran-1-yl)pyrid-z-ylmethanol: x = R, S; y = 7, 12; z = 3, 4) wre prepared and fully characterized. By means of variable-temperature NMR spectroscopy, different combinations of 螖-head-to-tail, head-to-head, and 螞-head-to-tail rotamers were identified, and the free energies of activation for Pt鈥揘 bond rotation were determined for the pyrid-4-yl complexes with 螖G鈥?/sup>307 = 16.1 卤 0.3 kcal mol鈥? and 螖G鈥?/sup>325 = 16.2 卤 0.5 kcal mol鈥? for the 1,7-carboranyl derivative and 螖G鈥?/sup>307 = 16.4 卤 0.5 kcal mol鈥? and 螖G鈥?/sup>325 = 16.2 卤 0.5 kcal mol鈥? for the 1,12-carboranyl derivative. The corresponding 2:1 host鈥揼uest 尾-cyclodextrin (尾-CD) adducts ([PtL2(phen)路2尾-CD](NO3)2) were also prepared and fully characterized by high resolution electrospray ionization mass spectrometry and 2D-1H{11B} nuclear Overhauser enhancement spectroscopy and rotating-frame Overhauser effect spectroscopy NMR experiments. The interaction of the novel supramolecular adducts with calf thymus DNA was investigated by means of linear dichroism, ultraviolet-visible spectroscopy, thermal denaturation, and isothermal titration calorimetry experiments which revealed a bimodal binding regime with DNA intercalation favored at low [drug]/[DNA] ratios, while at higher drug loading, surface aggregation was observed. Furthermore, the data were also consistent with some degree of dissociation of the 尾-CD host鈥揼uest adducts upon DNA binding. When we used a single binding-site model, interpreted as a weighted average of all of the possible equilibrium interactions, the compounds showed high affinity for ct-DNA with Kassoc ranging from (1.3 卤 0.1) 脳 105 M鈥? to (5.7 卤 0.4) 脳 105 M鈥?. In general, the overall DNA-binding behavior was enthalpically driven with a minor or unfavorable entropic component, which is consistent with the thermodynamics of an intercalation-dominated process. A higher degree of DNA intercalation was observed for the R-isomer in the pyrid-3-yl compounds, and the opposite trend was observed in the case of pyrid-4-yl derivatives.