Alemán Carlos, Jiménez Ana I, Cativiela Carlos, Pérez Juan J, Casanovas Jordi
Departament d'Enginyeria Química, E.T.S. d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Diagonal 647, E-08028 Barcelona, Spain.
J Phys Chem B. 2005 Jun 16;109(23):11836-41. doi: 10.1021/jp050141t.
The high pyramidalization of the bicyclic amide nitrogen found in the crystal structure of a dipeptide incorporating (1S,2S,4R)-N-benzoyl-2-phenyl-7-azabicyclo[2.2.1]heptane-1-carboxylic acid has been investigated using quantum mechanical calculations. More specifically, a bottom-up strategy based on the study of model molecules of progressive complexity has been used. First, an appropriate quantum mechanical method has been selected by examining the distortion of the amide bond in three simple model molecules. Next, the amide distortion induced by the norbornane ring has been evaluated by considering three different 7-azabicyclo[2.2.1]heptane amides. After this, the suitability of quantum mechanical calculations to predict the effect of the substituents on the pyramidalization of the bicyclic amide nitrogen has been investigated by comparing experimental and theoretical parameters for a number of compounds. Finally, the factors responsible for amide distortion in the (1S,2S,4R)-N-benzoyl-2-phenyl-7-azabicyclo[2.2.1]heptane-1-carboxylic acid derivative have been elucidated using a hierarchical approach. For this purpose, several derivatives were generated by removing or modifying the substituents attached to the 7-azanorbornane system. Results have been discussed in terms of intramolecular specific interactions.
利用量子力学计算研究了一种包含(1S,2S,4R)-N-苯甲酰基-2-苯基-7-氮杂双环[2.2.1]庚烷-1-羧酸的二肽晶体结构中双环酰胺氮的高锥形化。更具体地说，采用了一种基于对逐步复杂的模型分子进行研究的自下而上的策略。首先，通过研究三个简单模型分子中酰胺键的扭曲来选择合适的量子力学方法。接下来，通过考虑三种不同的7-氮杂双环[2.2.1]庚烷酰胺来评估降冰片烷环引起的酰胺扭曲。在此之后，通过比较多种化合物的实验和理论参数，研究了量子力学计算预测取代基对双环酰胺氮锥形化影响的适用性。最后，使用分级方法阐明了(1S,2S,4R)-N-苯甲酰基-2-苯基-7-氮杂双环[2.2.1]庚烷-1-羧酸衍生物中酰胺扭曲的原因。为此，通过去除或修饰连接在7-氮杂降冰片烷系统上的取代基生成了几种衍生物。已根据分子内特定相互作用对结果进行了讨论。
