Drug Structures Study Documents

what is a stereoisomer? molecule that has the same sequence of atoms in it's structure but differs in the 3D arrangement of bonds at one or more atoms what is the stereogenic centre? the atom that gives rise to stereoisomerism conformational isomerism - stereoisomers can be interconverted solely by the rotation of bonds what is the difference between conforconfigurational isomerism - stereoisomational and configurational isomerism? mers that can't be interconverted by rotation of bonds, main examples are optical isomerism and cis/trans isomerism what is cis/trans isomerism? stereoisomers differ in how groups are orientated either side of a double bond what are enantiomers aka optical isomers? pairs of compounds that are mirror images of each other, enantiomers have identical physical and chemical properties (melting points, density etc) but differ in that solutions of the compounds will rotate polarised light in opposite directions, arises due to the presence of chiral centres, type of configurational isomerism what is the word that describes a molecule that cannot be superimposed on its mirror image? chiral what is a chiral centre (or stereogenic centre)? an atom (usually carbon) that has FOUR different groups attached to it true or false - a chiral carbon is a carbon atom that is a chiral centre true a method for classifying the configuration what is the cahn-ingold-prelog (CIP) sysof atoms at a chiral centre, enantiomers tem? are designated R or S using this system how does the D/L system classify enan- based on their relationship to glyceraldetiomeric pairs? hyde (the simplest sugar) 1/6 how does the +/- system classify enantiomeric pairs? based on the direction they rotate polarised light (+) enantiomers rotate polarised light ______ (-) enantiomers rotate polarised light ______ clockwise anticlockwise what is a diastereomer? a pair of stereoisomers that contain chiral centres but are NOT mirror images of each other glycine which amino acid has hydrogen as their all other amino acids will have four differR group? ent substituents on the alpha carbon molecules that do not have a chiral centre are said to be ______ achiral name some of the conformational structures of cyclic sugar molecules chair and boat when does cis-trans isomerism aka geo- when there is a double bond or ring strucmetric isomerism occur? ture that prevents the rotation of a bond three - drug has chiral centre with four substituents shown as coloured spheres - to get maximum binding affinity the groups in the drug have to match those in the receptor if a protein selects between optical iso- - right enantiomer is a mirror image of the mers of a drug, how many points of at- left and can only attach to 2/3 sites no tachment must the drug make to the pro- matter how it is rotated tein? (left hand in a right handed glove analogy) what can be used to measure the rotation of polarised light? polarimeter 2/6 D/L system glyceralderhyde is chiral compounds that are considered structurally similar to (+)-glyceraldehyde are classified as ______ compounds that are considered structurally similar to (-)-glyceraldehyde are classified as ______ D L for the D/L classification system to be applicable there needs to be some obvious structural relationship between the compound in question and glyceraldehyde - therefore what compounds is the D/L system used on? sugars and amino acids the D/L rules cannot be directly applied noradrenaline has as amino acid precurto noradrenaline so why do you somesor (L-tyrosine) times see it names L-noradrenaline? true or false - back in history d/l were used to indicate optical activity true if a molecule is classified as R in the cahn ingold prelog system, what will it be in the D/L and +/- systems? b. we can't tell a. D, there is no way to predict the optical acb. we can't tell tivity from the R/S classification c. D, + d. L, + 1. find the chiral centre and prioritise substituents 2. figure out how the groups are oriented in 3D space and rotate the molecule so stages of classification using the CIP R/S that the lowest priority group faces into system the page 3. if the are ordered in highest to lowest priority in a clockwise direction the molecules is an R enantiomer, if the order is anticlockwise it is an S enantiomer 3/6 according to their atomic number if two or more of the substituents have the same atomic number then you how are the substituents around a chiral should rank the atoms bonded to them in centre prioritised? order of atomic number, go down the lists and find the first place there is a difference, the group containing the atom with the higher atomic number takes priority they should be treated as two/three sinwhen classifying using the CIP R/S sys- gle binds to the same type of atom tem how should double and triple bonds ie if a carbon is double-bonded to an oxywe dealt with? gen this should be considered a carbon with 2 single bonds to 2 oxygen atoms 3D arrangements can be represent in 2D by drawing bonds in a special way explain what the following lines indicate: solid wedge line standard line dashed line solid wedge - bonds coming out of the page standard - bonds that are in the plane of the page dashed - bonds going into the page hydrogen bonds what types of bond are normally omitted (except when they are shown on atoms from 3D structure drawings? like nitrogen and oxygen) what would an R enantiomer be classified in the D/L system? D true or false - molecules can have more than one chiral centre true when compounds with two chiral carbons differ in the configuration at both chiral carbons (ie 1R, 3R with 1S, 3S) they are ______ when they differ at only one chiral carbon they are not mirror images and therefore ______ (1R, 3R with 1R, 3S and 1S, 3R) enantiomers diastereomers n = 2^c c is the number of chiral centres 4/6 what formula can be used to calculate the number of stereoisomers of a compound? it is chiral and is the R enantiomer the lowest priority group (hydrogen) is already facing into the screen, the nitrogen is highest priority, followed by the describe the stereochemistry of this mol- CH2SH group and then the COOH group ecule (ordered anticlockwise) what is the only amino acid found in proteins that is an R enantiomer? cysteine what is the only achiral amino acid? glycine it is chiral and is the R enantiomer the OH group is pointing into the page and the H is not shown but we can infer it is pointing out the page, describe the stereochemistry of this mol- molecule has to be rotated so H faces into page, ecule the order of priority is OH, methylamino, catechol group (clockwise) it is achiral describe the stereochemistry of this molecule 8 there are 3 chiral carbons in this mole5/6 cule (carbons 2,3,4) 2^3 = 8 what is the total number of possible stereoisomers of this compound? it has multiple chiral centres the molecule is not symmetrical both carbons 3 and 7 have 4 different groups attached describe the stereochemistry of this molecule this is the RR version of this molecule (the other versions are RS, SR, SS) which enantiomer of noradrenaline binds (R)-noradrenaline binds 45x tighter than to ²2adrenoreceptors around 45x tighter (S)-noradrenaline than the other? what is a racemic mixture? one containing equal amounts of both enantiomers (50:50 mixture of R and S) 6/6