ISOMERS
Definition
Isomers are compounds that have the same molecular (empirical) formula but different structures and demonstrate physicochemical and pharmacological differences
Classification
Structural Isomers
Definition
Compounds with the same empirical formula but whose atoms are connected in a different sequence
Chain isomers
– have different branching patterns of carbon chains
Position isomers
– the functional group is located on different carbons in the chain
– tend to have similar chemical properties
Functional group isomers
– have different types of bonds and hence different functional groups
– tend to have very different chemical properties
Tautomers
– compounds in which under differing conditions eg pH the substituent groupings may alter their position
– structural isomers that readily convert from one isomeric form to another and hence exist in equilibrium
Stereoisomers
Definition
Compounds which have the same empirical formula and whose atoms are attached in the same sequence but differ in the spatial arrangement of the atoms
Significance
– may have marked pharmacokinetic and pharmacodynamic differences eg levobupivacaine is less cardiotoxic than dextrobupivacaine only levo isomer of morphine has opioid activity
– different 3 dimensional arrangement → different ability to interact with receptors enzymes and nonspecific binding sites
– isomerspecific ability of a drug to produce a pharmacological effect is evidence supporting the presence of receptors
Enantiomers
– stereoisomers that are nonsuperimposable mirror images (like left and right hands)
– contain a chiral centre (an asymmetric carbon with four different groups attached to it)
– identical physical properties except the direction in which they rotate polarised light
Classification Systems
a) Rotation of polarised light to the
left levorotatory l ()
right dextrototatory d (+)
a racemic mixture contains equal amounts of levo and dextro isomers and therefore has no overall rotating effect on polarised light
b) Cahn Ingold Prelog convention
Ligands around the chiral carbon are assigned a priority based on their atomic number
(higher atomic number higher priority)
Rectus (R) priorities increase in clockwise direction
Sinister (S) priorities increase in anticlockwise direction
Not important to know the exact priority rules Note that this system has nothing to do with
rotation of polarised light and therefore classification in one system does not always
correspond to the same classification in the other Coincidentally〞 this seemingly arbitrary nomenclature (R S) are the initials of Mr R S Cahn
c) Simple sugars and amino acids can be classified as D or L according to the clockwise or anticlockwise spatial arrangement of COOH NH3 H and hydrocarbon chain around the chiral carbon This is an old classification system don’t bother learning it just be aware of it
(D and L are not to be confused with d and l)
Diastereoisomers
– Stereoisomers with different orientation of substituent groups on either side of a rigid bond (eg double bond or ring structure)
– Alternatively can be thought of as isomers with two chiral carbons
Classification systems
a) cis and trans
cis functional groups are on the same side of the double bond
trans functional groups are on opposite sides of the double bond
eg mivacurium is presented as a mixture of isomers
transtrans 60
cistrans 30
ciscis 10
b) other systems include synanti and ZE (forget about this crap)
More detailed info on isomers can be found at
Classification of Isomers
Isomers Compounds that have identical chemical and molecular formulas but differ in the nature of sequence of bonding of their atoms or in their arrangement of atoms in space According to their topology they are classified as either structural or stereoisomers Isomers are broadly classified into two broad categories
11
Structural Isomers Compounds that have the same atoms present but differ in their order of connectivity They are also called as constitutional isomers They have the same molecular formula but different structures It can be distinguished by planar diagrams such as fischer projections
Skeletal Isomers Compounds that have the same functional groups but differ in the length of the side chains They are also called as chain isomers For example pentane 2methyl butane and 22 dimethyl propane
Positional Isomers Compounds that have the same functional groups but are present on different positions of the chain For example butan1ol and butan2ol
Functional Isomers Compounds that have different functional groups For example ethanol and methoxy methane
Tautomers Compounds whose structures differ in arrangement of atoms but which are in dynamic equilibrium with each other
1
KetoEnol tautomerism
2
RingChain isomerism seen in case of glucose
12
Stereoisomer Compounds that have the same chemical formula same atoms same connectivity and differ only in the arrangement of their atoms in space
Anomers Stereoisomers where the molecule is cyclized and the difference in configuration is about the anomeric carbon only In case of aldoses the anomeric carbon is C1 and for ketoses it is C2 eg sugar hemiacetal Glucose in open chain form is not chiral at C1 but in ring form has two optically active stereoisomers alpha & beta glucose
Rotamers and Conformers On the basis of spatial arrangement of atoms in the molecule that can be achieved by rotation(or torsion) around one or more single bonds they are classified as rotamers and conformers Conformers assume the chairboat and equitorialaxial forms Rotamers assume the different newmann projections (staggeredeclipsedgauche)
Configurational Isomers have a chiral (stereogenic center) Chiral center refers to a carbon atom attached to four different groups The molecule is said to possess chirality and to have a stereogenic
center
1
Enantiomer Stereoisomers that are nonidentical mirrorsymmetric for all atoms nonsuperimposable optically active (eg levodextrorotatory) inverted only by breaking bonds and remaking them in the reverse sense eg Dglucose and Lglucose
2
Diastereomer Stereoisomers that are not mirror images but have identical configuration for at least one asymmetric center and at least one different configuration for the remaining asymmetric centers eg Threonine has 2 chiral centers and therefore 4 diastereomers
21
Epimers They are a special case of diastereoisomerism where there is a difference for one and only one asymmetric center eg Dglucose and Dmannose Dglucose and Dgalactose are epimers
3
Mesoisomer (Achiral molecules) superimposable mirror images which have more than one stereogenic center Mesoisomers have two planes of symmetry the usual mirror plane of reflection and a second plane perpendicular to it through the molecule (in the ``middle＇＇ of the molecule) The asymmetric centers are distributed around this second place so that they are mirror inverses of each other Hence optical rotations from the two ``halves＇＇ of the molecule cancel out
4
Geometric Isomers Stereoisomers which are isomeric about double bonds If the bond is CC the terms are cistrans if the bond is CN the terms are syn (cislike) and anti (translike) For example cis2butene and trans2butene
Chiral Center Naming Classification
• + Indicates the direction in which plane of polarized light is rotated(clockwiseanticlockwise)
• DL (DextrorotatoryLevorotatory) Plane of polarized light is rotated to the right or left
• alphabeta stereochemistry of the anomeric carbon It is used for sugars
• RS convention The four groups surrounding the stereocenter are given a priority from a > d (from highest to lowest) The molecule is then observed from the side with the lowest priority group If the remaining three groups form a clockwise array (a>b>c) then it is R convention If it is in anticlockwise then S convention Priority is assigned according to atomic number with the higher the atomic number the higher the priority This is used for chiral molecules (enantiomersdiastereomersepimers)
• EZ convention The two groups attached to the carbon around the double bond are given the priority If the two highest priority groups are on the same side of the double bond then the molecule is given the Z convention(similar to cis) and if on the opposite side then E convention(similar to trans) eg 1chloro1bromo2iodoethene is differentiated on basis of EZ convention Priority is assigned according to the atomic number with the higher the atomic number the higher the priority Hyrdogen always has the lowest priority If there are two identical atoms attached to the stereocenter (say the carbon of the methyl group and carbon of the ethyl group) then work along the chain of the attached group until a difference occurs
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Definition
Isomers are compounds that have the same molecular (empirical) formula but different structures and demonstrate physicochemical and pharmacological differences
Classification
Structural Isomers
Definition
Compounds with the same empirical formula but whose atoms are connected in a different sequence
Chain isomers
– have different branching patterns of carbon chains
Position isomers
– the functional group is located on different carbons in the chain
– tend to have similar chemical properties
Functional group isomers
– have different types of bonds and hence different functional groups
– tend to have very different chemical properties
Tautomers
– compounds in which under differing conditions eg pH the substituent groupings may alter their position
– structural isomers that readily convert from one isomeric form to another and hence exist in equilibrium
Stereoisomers
Definition
Compounds which have the same empirical formula and whose atoms are attached in the same sequence but differ in the spatial arrangement of the atoms
Significance
– may have marked pharmacokinetic and pharmacodynamic differences eg levobupivacaine is less cardiotoxic than dextrobupivacaine only levo isomer of morphine has opioid activity
– different 3 dimensional arrangement → different ability to interact with receptors enzymes and nonspecific binding sites
– isomerspecific ability of a drug to produce a pharmacological effect is evidence supporting the presence of receptors
Enantiomers
– stereoisomers that are nonsuperimposable mirror images (like left and right hands)
– contain a chiral centre (an asymmetric carbon with four different groups attached to it)
– identical physical properties except the direction in which they rotate polarised light
Classification Systems
a) Rotation of polarised light to the
left levorotatory l ()
right dextrototatory d (+)
a racemic mixture contains equal amounts of levo and dextro isomers and therefore has no overall rotating effect on polarised light
b) Cahn Ingold Prelog convention
Ligands around the chiral carbon are assigned a priority based on their atomic number
(higher atomic number higher priority)
Rectus (R) priorities increase in clockwise direction
Sinister (S) priorities increase in anticlockwise direction
Not important to know the exact priority rules Note that this system has nothing to do with
rotation of polarised light and therefore classification in one system does not always
correspond to the same classification in the other Coincidentally〞 this seemingly arbitrary nomenclature (R S) are the initials of Mr R S Cahn
c) Simple sugars and amino acids can be classified as D or L according to the clockwise or anticlockwise spatial arrangement of COOH NH3 H and hydrocarbon chain around the chiral carbon This is an old classification system don’t bother learning it just be aware of it
(D and L are not to be confused with d and l)
Diastereoisomers
– Stereoisomers with different orientation of substituent groups on either side of a rigid bond (eg double bond or ring structure)
– Alternatively can be thought of as isomers with two chiral carbons
Classification systems
a) cis and trans
cis functional groups are on the same side of the double bond
trans functional groups are on opposite sides of the double bond
eg mivacurium is presented as a mixture of isomers
transtrans 60
cistrans 30
ciscis 10
b) other systems include synanti and ZE (forget about this crap)
More detailed info on isomers can be found at
Classification of Isomers
Isomers Compounds that have identical chemical and molecular formulas but differ in the nature of sequence of bonding of their atoms or in their arrangement of atoms in space According to their topology they are classified as either structural or stereoisomers Isomers are broadly classified into two broad categories
11
Structural Isomers Compounds that have the same atoms present but differ in their order of connectivity They are also called as constitutional isomers They have the same molecular formula but different structures It can be distinguished by planar diagrams such as fischer projections
Skeletal Isomers Compounds that have the same functional groups but differ in the length of the side chains They are also called as chain isomers For example pentane 2methyl butane and 22 dimethyl propane
Positional Isomers Compounds that have the same functional groups but are present on different positions of the chain For example butan1ol and butan2ol
Functional Isomers Compounds that have different functional groups For example ethanol and methoxy methane
Tautomers Compounds whose structures differ in arrangement of atoms but which are in dynamic equilibrium with each other
1
KetoEnol tautomerism
2
RingChain isomerism seen in case of glucose
12
Stereoisomer Compounds that have the same chemical formula same atoms same connectivity and differ only in the arrangement of their atoms in space
Anomers Stereoisomers where the molecule is cyclized and the difference in configuration is about the anomeric carbon only In case of aldoses the anomeric carbon is C1 and for ketoses it is C2 eg sugar hemiacetal Glucose in open chain form is not chiral at C1 but in ring form has two optically active stereoisomers alpha & beta glucose
Rotamers and Conformers On the basis of spatial arrangement of atoms in the molecule that can be achieved by rotation(or torsion) around one or more single bonds they are classified as rotamers and conformers Conformers assume the chairboat and equitorialaxial forms Rotamers assume the different newmann projections (staggeredeclipsedgauche)
Configurational Isomers have a chiral (stereogenic center) Chiral center refers to a carbon atom attached to four different groups The molecule is said to possess chirality and to have a stereogenic
center
1
Enantiomer Stereoisomers that are nonidentical mirrorsymmetric for all atoms nonsuperimposable optically active (eg levodextrorotatory) inverted only by breaking bonds and remaking them in the reverse sense eg Dglucose and Lglucose
2
Diastereomer Stereoisomers that are not mirror images but have identical configuration for at least one asymmetric center and at least one different configuration for the remaining asymmetric centers eg Threonine has 2 chiral centers and therefore 4 diastereomers
21
Epimers They are a special case of diastereoisomerism where there is a difference for one and only one asymmetric center eg Dglucose and Dmannose Dglucose and Dgalactose are epimers
3
Mesoisomer (Achiral molecules) superimposable mirror images which have more than one stereogenic center Mesoisomers have two planes of symmetry the usual mirror plane of reflection and a second plane perpendicular to it through the molecule (in the ``middle＇＇ of the molecule) The asymmetric centers are distributed around this second place so that they are mirror inverses of each other Hence optical rotations from the two ``halves＇＇ of the molecule cancel out
4
Geometric Isomers Stereoisomers which are isomeric about double bonds If the bond is CC the terms are cistrans if the bond is CN the terms are syn (cislike) and anti (translike) For example cis2butene and trans2butene
Chiral Center Naming Classification
• + Indicates the direction in which plane of polarized light is rotated(clockwiseanticlockwise)
• DL (DextrorotatoryLevorotatory) Plane of polarized light is rotated to the right or left
• alphabeta stereochemistry of the anomeric carbon It is used for sugars
• RS convention The four groups surrounding the stereocenter are given a priority from a > d (from highest to lowest) The molecule is then observed from the side with the lowest priority group If the remaining three groups form a clockwise array (a>b>c) then it is R convention If it is in anticlockwise then S convention Priority is assigned according to atomic number with the higher the atomic number the higher the priority This is used for chiral molecules (enantiomersdiastereomersepimers)
• EZ convention The two groups attached to the carbon around the double bond are given the priority If the two highest priority groups are on the same side of the double bond then the molecule is given the Z convention(similar to cis) and if on the opposite side then E convention(similar to trans) eg 1chloro1bromo2iodoethene is differentiated on basis of EZ convention Priority is assigned according to the atomic number with the higher the atomic number the higher the priority Hyrdogen always has the lowest priority If there are two identical atoms attached to the stereocenter (say the carbon of the methyl group and carbon of the ethyl group) then work along the chain of the attached group until a difference occurs
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