Lecture 2 Flashcards
what is conformation?
the spatial arrangement of atoms affording distinction between stereoisomers which can be interconverted by rotations about formally single bonds.
what is configuration?
the arrangement of atoms of a molecular eternity in space that distinguish stereoisomers.
what are the types of conformations?
eclipsed and staggered (balanced)
describe torsional strain.
strain resulting from eclipsed bonds.
describe van der waals strain (steric strain)
strain that results from atoms being too close together.
describe angle strain.
strain that results from distortion of bond angles from typical values. (Dictated by orbital hybridisation)
calculation for c-c bond angles for flat rings
180x(n-2)/n
n= number of c-c bonds that constitute the ring.
configuration of chiral molecules can affect…
their biological potency
z-configuration and e-configuration
Z = vascular targeting agent
E = biologically inactive
two examples of lipophilic interactions between aromatic rings in drug molecules and biological macromolecules.
- pi stacking
- intercalation
substituent hydrophobicity equation
pi x = log P x - log P h
pi x = substituent hydrophobicity constant of substituent x
P x = partition coefficient for substituted compound with substituent x
P h = partition coefficient for unsubstituted compound without substituent x
what is the substituent hydrophobicity constant?
pi x
the localised effect of functional groups on the lipophilicity of drug molecules.
what does the substituent hydrophobicity constant measure?
the substituent hydrophobicity compared to hydrogen.
what does a positive substituent hydrophobicity constant imply?
substituents are more hydrophobic than H
(e.g. F, Cl, Br, I)
what does a negative substituent hydrophobicity constant imply?
substituents are less hydrophobic than H
(e.g. OH, COOH, NH2, NO2, CONH2, CF3, C triple bond N, SH)
what happens in a single point change of functional groups within a series of convergent analogues?
pi can be used in equation instead of log P
what happens in a single point change of functional groups within a series of convergent analogues?
pi can be used in equation instead of log P
the inductive effect is divided into 2 groups depending on?
the strength of electron withdrawing
or
strength of electron donating nature in respect to hydrogen.
Negative inductive effect (-I) - (electron withdrawing group)
NH3+ > NO2 > CN > SO3H > CHO > CO > COOH > COCl > CONH2 > F > Cl > Br > I > OH > OR > NH2 > C6H5 > H
Positive inductive effect (+I) - (electron donating group)
C(CH3)3 > CH(CH3)2 > CH2CH3 > CH3 > H
the C-H bond is usually considered non-polar however…
-there is a partial positive charge on H atom & patrial negative charge on C atom
- H atom acts as electron donating group
- cumulative donation turns the alkyl moiety into an electron donating group
what is the mesomeric(M) / resonance(R) effect and how can this be visualised?
- the electron withdrawing or donating effect attributed to a substituent through delocalisation of p or pi electrons
- visualised by drawing various canonical forms.
what is a negative resonance or mesmeric effect (-M or -R) ?
electron withdrawing group through pi bond.
E.g. -NO2, Carbony group (C=O), -C≡N, -COOH, -SO3H etc.
what is a positive resonance or mesomeric effect (+M or +R) ?
electron donating group through pi bond.
E.g. -OH, -OR, -SH, -SR, -NH2, -NR2 etc.
what does the hammett substituent constant measure?
-assesses the electronic effects of a substituent on a benzene ring.
- quantifies idea of electron donating and withdrawing
- includes inductive and mesmeric/resonance effects
- assesses effects at m- and p- positions.
what does a positive hammett sunstituent constant mean?
-electron withdrawing substituents stabilize the carboxylate anion & increases acidity
what does a negative hammett sunstituent constant mean?
electron donating substituents destabilize carboxylate anion and decreases acidity.
hammett substituent constant calculation
sigma x = Log (K x / K h )
