SAALIHA VIVA - DISCUSSION

Question 1

Define R factor

Answer 1

• Signifies a measure of agreement between the aplitudes of the structure factors.
• It is calculated during each cycle of least-square structure refinement to assess progress and incorporates the observed and calculated diffraction data

Question 2

What is the least squares method?

Answer 2

• The R factor is calculated during each cycle of least-square structure refinement
• It’s a statistical method to fit a line to a set of data points.
• It’s a way of finding the line of best fit for a set of data points by minimizing the sum of the squares of the distances between the data points and the line.

Question 3

What does the R factor equation mean?

Answer 3

Sum of absolute difference between observed (Fo) and calculated (Fc) over the sum of the observed

Question 4

Is R-factor an indicator of accuracy or precision?

Answer 4

The R factor must always be treated with caution, as an indicator of precision and not accuracy.

• I used a low R-factor, this is not a good guide for the correctness of a structure
• So we can use a higher R-factor – this IS a good guide for incorrectness of a structure
• However, tendency to overrefine models

Question 5

Why was standard deviation useful?

Answer 5

• SD being an indicator of how dispersed the data is compared to the mean
• The SD value for COOH were lower than for CONH2, this is significant considering there were more hits for CONH2

Question 6

What does the lower SD value mean?

Answer 6

• ND has lower SD
• Lower SD = more concentrated around the mean = more concordant results = more accurate

Question 7

CONH2 has greater H bond lengths

Answer 7

• CONH2 has a greater H-bond length than COOH
• The greater the bond length, the weaker the bond
• However, the properties of CONH2 = two donor and two acceptor atoms, outlining the increased capability of amides to form H-bonds

Question 8

Why did I include experiment 3??

Answer 8

• Experiment 3 was carried out to provide a comparison of experiments 1 and 2.
• Admitedly, this experiment could have been developed on further. It was left on its own, and not much work was done it,
• by analysing both the intramolecular O-H and the N-H and analysing distance 2 (which was my hydrogen bond) in terms of N-H…O aswell.
• From this I could’ve compared the acceptor and the donor lengths.
• And compared it to experiment 1 and 2 individually.
• However table 6 + 7 which is the intramolecular O-H and N-H show little disparity between the expected for N-H…O and N-H, therefore it would not have provided that diff results

Question 9

Why is there a lower number of hits for neutron diffraction?

Answer 9

• ND requires access to a suitable source available at a limited number of highly specialised centres
• More challenging than X-ray diffraction.
• Time-consuming and expensive
• Some materials are more difficult to study using ND than XRD, which can further limit the amount of available data.

Question 10

Neutron radiation mentioned on pg 26. Is neutron diffraction and neutron radiation the same thing?

Answer 10

• No, they are different things.
• Neutron diffraction is a technique whereby a crystal structure is subjected to a high energy neutron in order to obtain a diffraction pattern, used to study the structure of materials at the atomic level.
• Whilst neutron radiation is a type of ionizing radiation that consists of neutrons that have been emitted from a radioactive source
• I meant it in the sense where the neutrons are being directed at the sample

Question 11

How do you calculate a hydrogen bond?

Answer 11

The distance between the donor and acceptor atoms
H-bond exists when the distance between the donor and acceptor atoms is less than the total of the:
* acceptor atom’s atomic radius (1.5Å),
* the H atom’s atomic radius (1.2Å)
* and the length of the link between the donor atom and the H atom (1Å)
* So the total of this is 3.5
* So H bonds exist when the total is less than 3.5
* Any more than this = pure dipole to dipole interaction

Question 12

What is a pure dipole to dipole interaction?

Answer 12

Type of intermolecular force that occurs between two polar molecules. In a polar molecule there is an uneven distribution of electrons = partial negative charge on one end of the molecule and a partial positive charge on the other end

Question 13

What makes a good H bond?

Answer 13

A study carried out by Sigala et al showed that in general, H-bonds have a distance of 2.8Å. Therefore, I compared my values to this 2.8 value.

Question 14

The X-ray bond lengths appear shorter, therefore the XRD model is shorter than the ND model, explain this concept

Answer 14

• My results showed that XRD models were shorter than ND models
• XRD technique assumes all atoms in the crystal are stationary.
• In reality, atoms are constantly vibrating due to thermal motion
• This can cause the XRD pattern to be broadened, leading to an apparent shortening of the bond length.
• Electron density around the atoms can be distorted by the presence of other atoms in the crystal, which can also affect the measured bond length.
• The electron distribution is displaced along the covalent X-H bond towards atom X. Atom X is the O, because O is more electron negative.

Answer 15

• O is more electron negative.
• O atom attracts the shared electrons in the covalent bonds more strongly than the hydrogen atoms do.
• electron distribution to be displaced towards the oxygen end of the molecule.
• Which causes the XRD bond lengths to appear shorter

Question 16

Define electronegativity?

Answer 16

Electronegativity is a measure of an atom’s ability to attract electrons towards itself in a covalent bond.

Question 17

What is IAM

Answer 17

• The independent atom model (IAM) is a simplified model of the electronic structure of a molecule that treats each atom in the molecule as if it were isolated from the others
• and atomic electron densities as spherical densities of independent atoms.

Question 18

What is a limitation of IAM?

Answer 18

A limitation of IAM includes the fact that it does not recognise the aspherical nature of atomic electron densities, lone pairs, and other interactions. Because of this IAM fails to correctly describe the position of H atoms, which only have one valence electron

Question 19

What is a study to overcome the limitation of IAM?

Answer 19

The Woińska et al study posed the question of whether it was feasible to accurately determine the location of H atoms and their related bond lengths from XRD to overcome the limitations of IAM. Using HAR.

Question 20

Define HAR

Answer 20

• Hirshfeld atom refinement is a method for refining crystal structures using XRD data.
• The method involves calculating the Hirshfeld surfaces of the atoms in the crystal,
• By comparing the calculated Hirshfeld surfaces with the experimental X-ray diffraction data, researchers can refine the positions of the atoms in the crystal and obtain a more accurate picture of the crystal structure.
• This method has been shown to be particularly useful for studying hydrogen atoms, which are typically difficult to locate using traditional X-ray diffraction techniques.

Question 21

What does page 30 para 1 mean? What is an electron density map?

Answer 21

An electron density map is a three-dimensional representation of the distribution of electrons in a molecule or crystal.

Question 22

How do we infer the location of the neighbouring H atom using the O atom?

Answer 22

• To identify heavy atoms in a crystal, the electron density map is examined to identify regions of high electron density
• Heavy atoms scatter X-rays more strongly than light atoms, which results in higher electron density around the heavy atoms in the electron density map.
• Heavy atoms will have a higher electrostatic potential than light atoms, which can be used to identify their positions in the molecule.

Question 23

What were the peaks notes in figure 10 and figure 16

Answer 23

It is suggested in a study by Lusi that these peaks represent the “free” H atoms.

Question 24

How do you fix a position of an atom? Refer to Lusi experiment

Answer 24

• In molecular modeling, the position of a hydrogen atom can be fixed.
• This is often done when the position of the hydrogen atom is known with high certainty, such as when it is part of a functional group that has been well characterized experimentally.
• Most refining software programmes give crystallographers the option of fixing the X-H bond distance in the riding model to a value that minimises the R factor to a “known” value established using other methods.

Question 25

Define riding model

Answer 25

• method for fixing the position of hydrogen atoms in a molecule.
• Assumes H atom is covalently bonded to a heavier atom, and that the bond length and angle are well defined.
• position of the H atom is fixed relative to the position of the heavier atom,
• By using the riding model, the positions of hydrogen atoms can be inferred from the positions of the heavier atoms, improving the accuracy of the model.

Question 26

Define AFIX lines

Answer 26

• AFIX lines are crystallographic symmetry operations that are used to fix the position of atoms in a crystal structure.
• They are used to describe the symmetry of the crystal

Question 27

What is the QUEST-routine on CSD mentioned on pg 31 and did I use it?

Answer 27

The QUEST routine is a search algorithm used in the Cambridge Structural Database (CSD) to identify potential matches for a given crystal structure.

• The QUEST algorithm allows users to search the CSD for structures that are similar to a given query structure,
• even if the query structure is not present in the database.
• usegul for identifying related structures or predicting the properties of a new molecule based on the properties of similar molecules.

Question 28

SC vs PC

Answer 28

Question 29

What are the disadvantages of PD?

Answer 29

• PD requires ca. 10mg of material for a satisfactory diffraction pattern
• not available in the very early stages of drug development.
• ambiguity in the identification of atoms with similar atomic numbers: C,O, N
• the structure determination of organic molecules difficult.
• This explains the lower number of hits for powder diffraction.
• Furthermore, structural details from PD are not as precise as SCD and it is not generally possible to refine H atoms.
• This technique does not readily permit localisation of the hydrogen atoms

Question 30

Briefly explain the number of hits with PD

Answer 30

• With ND we got 0 powder hits for COOH and COOH + CONH2
• In general there were very few powder hits compared to the ample single crystal hits.

Question 31

What was the reason for the inclusion of PD?

Answer 31

• Redman-Furey et al
• the structural analysis an anhydrate form of risedronate sodium anhydrate
• Rietveld refinement of a high-quality X-ray powder diffraction pattern,
• Single vs powder analysis
• This study showed that powder X-ray diffraction was the more effective technique to yield the most accurate results for the structure of risedronate sodium anhydrate

Question 32

What is the limitation of results obtained from PD?

Answer 32

A key limitation of PD is that larger lattices may result in an overlap of the powder diffraction peaks and prevent the extraction of accurate intensities. The peak overlap seen in powder ND can be avoided using the Rietveld refinement method.

Question 33

Explain Rietveld refinement

Answer 33

• Method X-ray and neutron diffraction to refine crystal structures by fitting the observed diffraction pattern to a model of the crystal structure.
• Hugo Rietveld 1960s and has since become a widely used technique for analyzing crystal structures.
• The Rietveld refinement method is particularly useful for analyzing complex crystal structures, such as those with multiple phases or disorder. It can also be used to refine the crystal structure of a material as it undergoes a phase transition, allowing researchers to study the structural changes that occur as a material is heated or cooled.
• The fundamental concept is based on simulating a numerical powder neutron diffraction pattern that is specified by a set of parameters, hence why the inclusion of
• A key limitation of PD is that larger lattices may result in an overlap of the powder diffraction peaks and prevent the extraction of accurate intensities. The peak overlap seen in powder ND can be avoided using the Rietveld refinement method.
• The crystal structure is deemed refined once a good match is made between the calculated pattern and the experimental data.
• However, this could not be successfully incorporated in my project due to the limited data available.