L2 - The role of carbon in drug molecules

what is a conformation

the spatial arrangement of the atoms affording distinction between stereoisomers which can be interconverted by rotations about formally single bond

what is a configuration

the arrangements of atoms of a molecular entity in space that distinguishes sterroisomers

what can be converted by rotations from single sigma bonds

conformations

what are two forms of conformations

eclipsed and staggered

what is torsional strain

strain that results from eclipsed bonds

what is van der waals strain

strain the results rom atomes being too close together

what is angle strain

strain that results from distortion of bond angles from typical values

formula to calculate stability of saturated cyclic hydrocarbons

what can affect biological potency

the configuration of chiral molecules

what is the easson and stedman 3 points of interactiojn hypothesis

• three points of contact with drug binding site

• strong interactions and that drug is active

• rotation leads to 1 point of contact

what does rotation lead to in enatomers

only 1 point of contact

why is a double bond important in unsaturated hydrocarbons like z configuration and e configuration

introduces a space that prevents free rotation around that bond

what are wo examples of lipophilic interactions between aromatic rings in drug molecules and biological macromolecules

n stacking and intercalation

what is the substutuent hydriphobicity constant

a measure of the subsitiuent hydrophobicity compared to hydrogen

basically tells us how hydrophobic or hydrophilic a chemical group (substituent) is compared to hydrogen.

what does positive and negative values imply in the substutuent hydriphobicity constant

positive - more hydrophobic than H

negative - less hydrophobic than H

when pi can be used instead of p

what is the inductive effect in sigma bonds

pushing and pulling of electrons through sigma bonds due to te electronegativitiy of atoms or substiuents attached to a molecules

its like a tug of war

what is the positive inductive effect

when a group pushes away from itself though sigma bonds

what groups are normally in the positive inductive effect

alkyl groups

what is the negative inductive effect

when a group pulls electrons toward itself through sigma bonds

what atoms / groups have a negative inductive effect

those with high electronegativity values such as NO2, CL, COOH

what does the hammet substiuent constant

• assesses the electronice effecrs of a substiruent on a benzene ring

what does the mesomeric (resonance) effect refer to

the way electron density is delocalized in a molecule through pi or p bonds.

when does the mesomeric effect take place

when electrons are shifted through bonds in a way that stabilises or dstabilises the molecule

what are the two types of mesomeric effects

+m OR -M

when does the mesomeric +M effect occur

occurs when a group donates electron density through pi bonds

what is the effect from the +M mesomeric effect

it makes the attached atom or molecule more electron rich

what are some examples of +M groups

-OH , -NH2

why is the +M effect more stable and less likely to react

as the groups involved have lone pairs ( like oxygen in OH) that participate in resonance / delocalisation with the pi system donating electrons to it.

when does the -effect occur

when a group withdraws electron density away from the molecule

what is the effec of -M mesomeric

makes attached atom or molecules electron deficient

ecamples of -M groups

NO2, C00H

why is the -M mesomeric effect more reactive and acidic

they participate in delocalisation / resonance by pulling electron density away from the system.

whats the difference between the mesomeric effect and inductive effecr

inductive - happens through sigma bonds, permanent and based on electronegativity

mesomeric effect - happens through pi and p bonds, resonance driven and involves lone pairs or double bonds

what is the hammett subsituent constant σ

• number used to measure the electron-withdrawing or electron-donating effect of a substituent group on an aromatic ring.

what does the hammet constant help quantify

the mesometic and inductive effects of substituents.

what does the hammet constant help us predict

the rate of a reaction or the position where a new group will be added on the ring

formula for hammet constant + example picture

σ=log(Khydrogen/ ​Ksubstituted​​)

• Kₓ is the equilibrium constant (or rate constant) for a reaction with a substituted molecule (substituent X).

• Kₓ₀ is the equilibrium constant (or rate constant) for the same reaction with hydrogen as the substituent (i.e., without any substituent on the aromatic ring).

electron withdrawing groups and donating groups postitve or negative σ

withdrawing - positive σ

-donating - negative σ