SAALIHA VIVA - INTRO

Question 1

Define crystal structure and unit cell

Answer 1

• A crystal structure is defined as the repeating arrangement of atoms throughout a crystal.
• The unit cell is the smallest group of atoms that enables identical cells to be stacked on top of each other to completely fill a space
• An entire crystal structure can be created by the repetition of cells in three dimensions

Question 2

Define Laue spots

Answer 2

• The Laue method is used extensively for the determination of the orientation of single crystals
• Laue spots are bright spots formed when X-rays are diffracted by a crystal lattice

Question 3

Amorphous vs crystalline structure

Answer 3

Question 4

Define H bonds

Answer 4

Electrostatic interaction that occurs between molecules containing hydrogen and another electronegative atom such as O, N or a halogen

Question 5

Importance of H bonding

Answer 5

• Unique properties of H2O - high boiling point and surface temperature
• Protein binding and DNA structure
• Designing new material
• Identifying polymorphs

Question 6

Ritanovir

Answer 6

HIV treatment Ritonavir. Ritonavir is a polymorphic drug
- LHP method was used to identify the probability of H-bond formation to assess crystal stability based on H-bonding
- This can differentiate between a drug being effective or ineffective in industry
- H-bond geometry from the CSD

Question 7

Explain salt-cocrystal continuum

Answer 7

• Concept which describes the relationship between salts and cocrystals
• The continuum refers to the fact that there is a range of possible combinations (between API and a coformer) of drug molecules that can form either a salt or a co-crystal.
• The location of the H ion is what differentiates the two

Question 8

Coformers

Answer 8

Conformational isomers
- stereoisomers produced by rotation about a single bond

Question 9

What is the difference between a salt and a cocrystal?

Answer 9

Question 10

Rationale for salt co-crystal continuum

Answer 10

• Co-crystallisation is an important concept which has only recently gained widespread attention as a means of identifying the H atom position.
• A study by Edwards et al describes the two states where the H-atom is either situated close to the proton donor (co-crystal) or close to the proton acceptor

Question 11

Define bond length

Answer 11

Geometrical descriptor used throughout this report to analyse data, characterised by the distance between the centres of the two covalently bonded atoms.

Measured in Angstroms

Question 12

Define covalent bond

Answer 12

A covalent bond is defined as the sharing of electrons whereby the electrons from two different atoms share the orbital, binding the two atoms together.

Question 13

What does a higher bond order mean?

Answer 13

Means a shorter bond length due to the stronger pull between the two atoms

Question 14

Define elastic scattering in terms of XRD

Answer 14

• An incoming X-ray interacts with a crystal structure
• X-ray’s energy is absorbed
• And then scattered by the atom’s electrons
• Then released as a new X-ray after impact.

Question 15

How does the number of electrons effect how light is scattered?

Answer 15

• Atoms in these crystals are arranged in a regular pattern and are each surrounded by a cloud of electrons
• This allows them to diffract light.
• Each atom can be thought of as a coherent point scatterer.
• The number of electrons surrounding an atom determines how strongly it scatters light

Question 16

What are the advantages of XRD

Answer 16

• Can create 3D representation of the density of electrons within the crystal with the help of a computer programme by analysing the angles and intensities of these diffracted beams
• X-ray sources are so accessible and reasonably priced, the X-ray diffractometer is the most frequently utilised diffraction technique in solid-state laboratories.

Question 17

H atoms and XRD

Answer 17

• The more electrons an atom has, the greater it diffracts.
• Because H only has one electron, it makes it difficult to determine the precise position of H atoms, especially in the presence of heavy atoms that dominate the diffraction pattern

Question 18

SCXRD vs PXRD

Answer 18

Question 19

How are single crystals formed?

Answer 19

1. Slow diffusion – solution of compound of interest is place in a solvent that is less miscible with the original solvent. Overtime, solvent diffuses slowly into the solution = single crystals
2. Sublimation – heat compound of interest, to a temp at which is vaporises. Cool vapor, condense on a cooler surface

Question 20

Define ND

Answer 20

• Technique used to study the atomic structure of materials.
• It involves directing a beam of neutrons at a sample, and then analyzing the way the neutrons scatter to determine the positions of atoms within the sample.

Question 21

The role of neutrons in ND

Answer 21

• By subjecting materials to high-energy neutrons, some will be absorbed others will emerge in a new direction, known as scattered neutrons
• With or without a change in energy
• The rest will pass through the material unaffected.
• Neutrons interact with nuclei and lose energy in the process.

Question 22

Why is ND preferred for locating the position of H atom?

Answer 22

• In contrast to X-rays, neutrons interact with the atom’s nucleus rather than its electron shell, specifically with its spin
• Scattering power is not effected by the fact that hydrogen only has one electron.
• Therefore, provides accurate structural data on H atom locations

Question 23

Difference between XRD and ND

Answer 23

Question 24

Summarise Aims

Answer 24

• Study the usefulness of the H atom in the CSD for common H-bonding patterns
• COOH and CONH2 were investigated
• 3 distances were defined for each motif following common H bonding synthons
• Bond length entries derived from the CSD were imported and analysed
• Subjected to both XRD and ND
• Crystal structures were subjected to further refinement methods, by specifying the R factor ≤0.05, and powder vs single crystal diffraction, to identify which analytical tool would determine the H atom most accurately.