Bologna Fabio, Mattioli Edoardo Jun, Bottoni Andrea, Zerbetto Francesco, Calvaresi Matteo
Dipartimento di Chimica "Giacomo Ciamician", Alma Mater Studiorum-Università di Bologna, via F. Selmi 2, 40126 Bologna, Italy.
ACS Omega. 2018 Oct 22;3(10):13782-13789. doi: 10.1021/acsomega.8b01888. eCollection 2018 Oct 31.
Endohedral metallofullerenes (EMFs) have great potential as radioisotope carriers for nuclear medicine and as contrast agents for X-ray and magnetic resonance imaging. EMFs have still important restrictions for their use due to low solubility in physiological environments, low biocompatibility, nonspecific cellular uptake, and a strong dependence of their peculiar properties on physiological parameters, such as pH and salt content. Conjugation of the EMFs with proteins can overcome many of these limitations. Here we investigated the thermodynamics of binding of a model EMF (Gd@C) with a protein (lysozyme) that is known to act as a host for the empty fullerene. As a rule, even if the shape of an EMF is exactly the same as that of the related fullerene, the interactions with a protein are significantly different. The estimated interaction energy (Δ ) between Gd@C and lysozyme is -18.7 kcal mol, suggesting the possibility of using proteins as supramolecular carriers for EMFs. π-π stacking, hydrophobic interactions, surfactant-like interactions, and electrostatic interactions govern the formation of the hybrid between Gd@C and lysozyme. The comparison of the energy contributions to the binding between C or Gd@C and lysozyme suggests that, although shape complementarity remains the driving force of the binding, the presence of electron transfer from the gadolinium atom to the carbon cage induces a charge distribution on the fullerene cage that strongly affects its interaction with the protein.
内嵌金属富勒烯（EMFs）作为核医学中的放射性同位素载体以及X射线和磁共振成像的造影剂具有巨大潜力。由于在生理环境中的低溶解度、低生物相容性、非特异性细胞摄取以及其特殊性质对生理参数（如pH值和盐含量）的强烈依赖性，EMFs在使用上仍存在重要限制。将EMFs与蛋白质共轭可以克服其中许多限制。在此，我们研究了一种模型EMF（Gd@C）与一种已知可作为空富勒烯宿主的蛋白质（溶菌酶）结合的热力学。通常，即使EMF的形状与相关富勒烯完全相同，其与蛋白质的相互作用也存在显著差异。Gd@C与溶菌酶之间的估计相互作用能（Δ ）为-18.7 kcal/mol，这表明使用蛋白质作为EMFs的超分子载体具有可能性。π-π堆积、疏水相互作用、类似表面活性剂的相互作用以及静电相互作用决定了Gd@C与溶菌酶之间杂化物的形成。对C或Gd@C与溶菌酶结合的能量贡献的比较表明，尽管形状互补性仍然是结合的驱动力，但从钆原子到碳笼的电子转移的存在会在富勒烯笼上诱导电荷分布，这强烈影响其与蛋白质的相互作用。
