X-ray structure analysis of some molecules of biological interest

Abstract

The thesis entitled “X?ray Structure Analysis of Some Molecules of Biological Interest” consists of two parts. Part I (Chapters 1, 2, and 3) deals with studies on the geometry of an amide group under different chemical environments. Part II (Chapter 4) discusses the structure of a synthetic steroid molecule.

Chapter 1 This chapter gives a brief introduction to the geometry and conformation of peptides. Various examples show that molecular geometry can be affected by hydrogen bonding. In order to understand peptide geometry in the absence of any hydrogen bonding, a tertiary amide (where the hydrogen of the peptide group is replaced by a substituent) was studied. The compound N?acetyl?4,N?dimethyl?6?(N?acetyl?p?toluidinomethyl)aniline (I) crystallises in the triclinic space group P1 with: a = 12.999(9), b = 8.911(4), c = 9.199(5) Å; ? = 100.56(3)°, ? = 113.50(4)°, ? = 92.53(3)°, and Z = 2. The structure was solved using the direct?methods program MULTAN after some initial difficulty; therefore, a brief discussion on the reasons for the failure of MULTAN and ways to overcome them is given. The structure has been refined to an R?value of 0.066 for 2585 reflections measured on a diffractometer. One of the amide groups is disordered, whereby N(11), a substituent on the benzene ring, is displaced considerably out of the benzene plane. Absence of hydrogen bonding has increased the central peptide bond N(1)–C(8) to 1.363(4) Å from the accepted value of 1.325 Å for this bond. Also, the C(9)–C(8) bond length [1.487(5) Å] is shorter and the N(1)–C(10) length [1.462(4) Å] is longer than the corresponding normal peptide bond lengths. The peptide nitrogen N(1) shows significant pyramidal character, the deviation of the atom from its bonded neighbours being 0.022 Å. In this connection, an attempt was made to determine the nature of pyramidalisation in an sp²?hybridised nitrogen atom in a similar system, N?nitrosoamine. The crystal structure of 4,4??N,N??tetramethyl?N,N??dinitroso?2,2??methylenedianiline (II) was solved, and both N(1) and N(11) were found to exhibit pyramidal character, their deviations from the plane defined by their bonded neighbours being 0.023 and 0.049 Å respectively.

Chapter 2 The binding of alkali and alkaline?earth metal salts to the peptide bond is significant in understanding a variety of biological phenomena—conformational transitions of polypeptides and proteins, ion?complexation by macrocyclic antibiotic ionophores, and so on. Although interactions of model amides with alkali and alkaline?earth metal cations have been studied using quantum?mechanical calculations and vibrational and NMR spectroscopy, crystallographic data on such interactions are scarce. In view of this, a systematic crystallographic investigation of N?methylacetamide (NMA) (III) complexes of Li, Na, K, Mg, and Ca has been carried out. The complexes were prepared by heating appropriate amounts of the salt and NMA or by heating the two under reflux in a suitable solvent. Intensity data were collected on a CAD?4 diffractometer. The structures were solved using the heavy?atom technique and refined by full?matrix least?squares procedures. The chemical compositions and crystal data of the complexes are as follows: