Three-Dimensional Structures of Molecules

The design of the database that holds the three-dimensional information influences the ease with which different types of searches will be carried out. Obviously if a particular type of information is not present, searches cannot be performed on that type of information. 

The classic database of three-dimensional molecular struaures is the Cambridge Structural Database. It contains evaluated small-molecule and polymer X-ray and neutron diffraction data for more than 70,000 compounds. The database grows at the rate of 10% per year. It contains the connection table of each structure (frequently a complex or solvate), the bibliographic 

Several programs described in this review access a database derived from the Cambridge Structural Database. Jakes et al. ° and Desjarlais et al. include only the atom name and coordinates of the heavy atoms of the molecules. 

Molecular Design Limited has recently extended their MACCS-II chemical database system to MACCS-3D, for the storage and retrieval of three-dimensional atomic coordinates. Physical and biological data may be stored. A novel feature of MACCS-3D is the ability to recognize and remove duplicate coordinate sets. Coordinate sets can be retrieved from the database by specifying a combination of numerical and textual queries or by substructure. 

The main depository for the three-dimensional structure of biomacromolecules is the Brookhaven Protein Data Bank. It contains atomic coordinates of proteins and nucleic acids derived from single-crystal X-ray or neutron diffraaion studies. The data are deposited by the crystallographic community. Of the 1,200 macromolecules that have been studied by dif- 

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Since the three-dimensional structure of molecules is so tightly linked to their chemical and biological properties, we are going to encounter mnltiple examples of stereoisomerism as we move forward. So it seems reasonable and nsefnl to make a little snmmary of what we have said abont them here. 

Some computer programs show the three-dimensional structure of molecules as an aid to designing drugs that can be used against those molecules. (G. Tompkinson/Photo Researchers, Inc.)... 

Schuur, J. H., Selzer, P., and Gasteiger, J. (1996) The coding of the three-dimensional structure of molecules by molecular transforms and its application to structure-spectra correlations and studies of biological activity. J. Chem. Inf. Comput. Sci. 36, 334-344. 

Pfennig, B. W., and R. L. Frock, The use of molecular modeling and VSEPR theory in the undergraduate curriculum to predict the three-dimensional structure of molecules , J. Chem. Educ., 76,1018-1022 (1999). 

Y" u Brian W. Pfennig and Richard >U L. Frock, "The Use of Molecular Modeling and VSEPR Theory in the Undergraduate Curriculum to Predict the Three-Dimensional Structure of Molecules," /. Chem. Educ., Vol. 76,1999,1018-1022. 

Other common methods for representing the three-dimensional structures of molecules include Newman projections for showing conformational relationships and sawhorse figures. Newman projections look down a carbon-carbon bond so that the front carbon, designated by a circle, obscures the carbon directly behind it. Valences (bonds) to the front carbon extend to the center of the circle, while bonds to the rear carbon stop at the circle. Sawhorse projections have the carbon-carbon bond at oblique angles, which attempts to represent a perspective drawing of the molecule. Thus for 2-chloro butane, if one chooses to examine the 2,3 bond, then the sawhorse and Newman projections would be... 

The three-dimensional structure of molecules is important, because it affects both chemical reactivity and biological activity. The number of bonds the carbon atom is involved in is important in this respect, because it affects whether the molecule is planar (i.e. flat) or non-planar. Since the angle between the sp3 orbitals is 109.5°, alkanes (a chain of carbon atoms connected via single bonds) cannot lie in a flat plane. A double bond, however, confines the neighboring single bonds to a plane. Hence, because of the conjugated structure, the benzene ring is planar. 

Study of the chemical evolution of chirality started in 1809 with the discovery of Haiiy [4], who postulated from crystal cleavage observations that a crystal and each of its constituent space-filling molecules are images of each other in overall shape. Later, in 1848, Pasteur reported the different destruction rates of the dextro- and levorotatory forms of ammonium tartrate by the mold Penicillium glaucum [5]. These observations could not be explained properly at that time, but in 1874 Le Bel [6] and van t Hoff [7] independently proposed that the four valences of the carbon atom are directed toward the vertices of an atom-centered tetrahedron. This finding allowed the development of the theory of the three-dimensional structure of molecules by which the phenomenon of chirality and Pasteur s discovery were explained scientifically. 

Hydrogen bonding between molecules in the solid and liquid phases naturally tends to enhance the melting/boiling points of molecular substances, and plays an important part in determining the three-dimensional structures of molecules and crystals. 

Louis Pasteur (1822-1895), French chemist, discovers molecular asymmetry and demonstrates the existence of isomers, becoming one of the earliest scientists to deal with the three-dimensional structure of molecules. 

In addition to X-ray diffraction and NMR, which are direct techniques, methods based on the calculation of predicted three-dimensional structures of molecules in the range of 3 to 50 amino acids based on energy considerations are under rapid development. These approaches use what are commonly called molecular dynamics and energy minimization equations to specify the most probable conformation of polypeptides and small proteins. Often, when combined with information from other sources, such as X-ray crystallography or NMR studies, they have been demonstrated to be quite useful. However, when standing alone, their power and the accuracy of their predictive capability remains to be seen. 

An understanding of the three-dimensional structures of molecules has played an important part in the development of organic chemistry. The first experiments of importance to this area were reported in 1815 by the French physicist J. B. Biot, who discovered that certain organic compounds, such as turpentine, sugar, camphor, and tartaric acid, were optically active that is, solutions of these compounds rotated the plane of polarisation of plane-polarized light. Of course, the chemists of this period had no idea of what caused a compound to be optically active because atomic theory was just being developed and the concepts of valence and stereochemistry would not be discovered until far in the future. 

Stereochemistry is the study of the three-dimensional structure of molecules. No one can understand organic chemistry, biochemistry, or biology without using stereochemistry. Biological systems are exquisitely selective, and they often discriminate between molecules with subtle stereochemical differences. We have seen (Section 2-8) that isomers are grouped into two broad classes constitutional isomers and stereoisomers. Constitutional isomers (structural isomers) differ in their bonding sequence their atoms are connected differently. Stereoisomers have the same bonding sequence, but they differ in the orientation of their atoms in space. 

Strictly speaking, the availability of single-enantiomer compounds is not a future trend since some of them have already made an entry into clinical medicine. However, this technique s full potential is still unrealized, and it may lead to increased availability of many better and safer medications. The field of stereochemistry, which deals with the three-dimensional structure of molecules, teaches us that chemical compounds, medications included, can occur as a mixture of molecules whose structures are mirror images of each other. This means that two molecules that are otherwise identical may be spatially oriented in opposite directions, say, one to the right, the other to the left. Molecules so characterized are called enantiomers. 

Stereochemistry (Sections 4.9, 5.1) The three-dimensional structure of molecules. 

Stereochemistry Stereochemistry (the three-dimensional structure of molecules) is introduced early (Chapter 5) and reinforced often, so students have every opportunity to learn and understand a crucial concept in modem chemical research, drug design, and synthesis. 

The illustration program is a key component of the visual emphasis in Organic Chemistry. Besides traditional skeletal (line) structures and condensed formulas, there are numerous ball-and-stick molecular models and electrostatic potential maps to help students grasp the three-dimensional structure of molecules (including stereochemistry) and to better understand the distribution of electronic change. 

The authors of a biochemistry text face the problem of trying to present three-dimensional molecules in the two dimensions available on the printed page. The interplay between the three-dimensional structures of hiomolecules and their biological functions will be discussed extensively throughout this hook. Toward this end, we will frequently use representations that, although of necessity are rendered in two dimensions, emphasize the three-dimensional structures of molecules. 

To understand the forces behind the three-dimensional structure of molecules, we need to refer back to an earlier analogy. We said that the nucleus of the atom, being made up of protons and neutrons, is thousands of times as massive than the electrons that surround it. The electrons, we continued, are like fleas on an elephant. But though the fleas are small, they certainly influence the behavior of the elephant, and three-dimen-... 

Schuur, J., Selzer, R and Gasteiger, J. (1996). The Coding of the Three-Dimensional Structure of Molecules by Molecular Transforms and Its Application to Structure-Spectra Correlations and Studies of Biological Activity. J. Chem.Inf. Comput.Set, 36,334-344. 

Stereochemistry is defined as the study of the three-dimensional structure of molecules. Stereochemical considerations are important in both isomerism and studies of the mechanisms of chemical reactions. Implicit in a mechanism is the stereochemistry of the reaction in other words, the relative three-dimensional orientation of the reacting particles at any time in the reaction. 

As is well known, van t Hoff played a central role in convincing chemists that the three-dimensional structure of molecules could be both apprehended and accurately represented, and it would be easy to categorize him as a naive realist with respect to... 

Descriptors based on the three-dimensional structure of molecules are applied when sets of structurally diverse compounds must be compared. The time needed for the calculations may exceed several minutes or even hours. 

Many years later, it was found that this characteristic of the descriptor could be used for the correlation of biological activity and three-dimensional structure of molecules. The activity of a compound also depends on the distances between atoms (such as H-bond donors or acceptors) in the molecular structure [91]. Adaptation of the RBF function to biological activity led to the so-called 3D-MoRSE code (3D-Molecule Representation of Structures based on Electron diffraction) [92]. The method of RBF calculation can be simplified in order to derive a descriptor that includes significant information and that can be calculated rapidly ... 

Models can help you visualize the three-dimensional structures of molecules. Consider the simplest molecule that exists—hydrogen, H2. Two hydrogen atoms share a pair of electrons in a nonpolar covalent bond, as shown in the electron dot structure. 

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