Intermolecular interactions

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Intermolecular interactions

  1. 1. ENERGY COMPONENTS FOR INTERMOLECULAR NON-COVALENT INTERACTIONS DEPARTMENT OF PHARMACEUTICAL CHEMISTRY MCOPS SUBMITTED TO SUBMITTED BY DR.JAYASHREE.B.S SHIKHA TYAGI PROFESSOR 100602017
  2. 2. CONTENTS1 INTRODUCTION2 ENERGY COMPONENTS FOR INTERMOLECULAR NONCOVALENTINTERACTIONS•ELECTROSTATIC ENERGY• EXCHANGE REPULSION ENERGY• POLARIZATION ENERGY•CHARGE TRANSFER ENERGY• DISPERSION ATTRACTION• SUMMARY
  3. 3. INTRODUCTION Supramolecular chemistry THE FORCES THAT HOLD TOGETHER LARGE AND SMALLMOLECULES, PARTICULARLY WHERE THE LARGE MOLECULE IS APROTEIN OR NUCLEIC ACID AND THE SMALL MOLECULE IS ANINHIBITOR OR SUBSTRATEFORCES BETWEEN ATOMS ARE CONVENTIONALLY DIVIDED INTO THE TWOCATEGORIES OF COVALENT AND NONCOVALENT "BONDS."DRUG-RECEPTOR INTERACTIONS, ON THE OTHER HAND, ARE GENERALLYINFLUENCED MOST BY WEAKER, NONCOVALENT "BONDS," WHERE ELECTRONPAIRS ARE "CONSERVED" IN REACTANTS AND PRODUCTS.EXAMPLE
  4. 4. POTENTIAL ENERGY CURVES FOR COVALENT AND NONCOVALENT INTERACTIONS BETWEEN TWO ATOMSTHE FRACTION OF "BROKEN" BONDS AT EQUILIBRIUM IS
  5. 5. WEAKNESS OF NONCOVALENT BONDS MAKES THEM VERY USEFUL INBIOLOGICAL PROCESSES, BECAUSE A SMALL CHANGE IN THE CHEMICALENVIRONMENT (SUCH AS TEMPERATURE, CONCENTRATIONS, OR IONICSTRENGTH) CAN FORM OR BREAK SUCH A BONDBEST KNOWN IMPORTANT EXAMPLES OF NONCOVALENT BONDS•BETWEEN THE STRANDS OF DNA, WHERE HYDROGEN BONDS HOLD THEDOUBLE HELIX TOGETHER. BETWEEN ENZYME AND SUBSTRATE.•"RECEPTOR" PROTEIN AND HORMONE,•ANTIBODY AND ANTIGEN•INTERCALATOR AND DNA.
  6. 6. ENERGY COMPONENTS FOR INTERMOLECULAR NONCOVALENT INTERACTIONSkf = The rate constant for association of the complexkr = The rate constant for dissociation of the complexKas = kf/kr affinity, or association constantThe biological activity of a drug is related to its affinity Kas for the receptor,
  7. 7. THE THERMODYNAMIC PARAMETERS OF INTEREST FOR THEREACTIONS ENTROPY ∆S ENTHALPY ∆H STANDARD FREE ENERGY (∆G"), THESE ARE RELATED BY THE EQUATION
  8. 8. ENERGY COMPONENTS•ELECTROSTATIC ENERGY•EXCHANGE REPULSION ENERGY•POLARIZATION ENERGY•CHARGE TRANSFER ENERGY•DISPERSION ATTARACTION
  9. 9. ELECTROSTATIC ENERGYENERGY BETWEEN THE TWO CHARGESALTHOUGH THE CHARGE DUE TO ELECTRON CLOUD IS SMEARED AROUNDTHE MOLECULE BUT FOR PRACTICALLY WE CAN CONSISER IT AS CONDENSED ASPOINT CHARGETHIS BASED ON THE COULAMB’S LAW DIRECTIONALITY AND THE STRENGTH OFTHE ELECTROSTATIC ENERGY DEPENDS ON THE MULTIPLE MOMENTS
  10. 10. OF THE INTERMOLECULAR ENERGY COMPONENTS, THEELECTROSTATIC IS THE LONGEST RANGEION-ION INTERACTIONS DIE OFF AS 1/R; ION-DIPOLE AS 1/R2; DIPOLE-DIPOLE AS 1/R3.
  11. 11. Selective Binding of Antiinfluenza Drugs and Their Analogues to ‘Open’ and ‘Closed’ Conformations of H5N1 Neuraminidase
  12. 12. EXCHANGE REPULSION ENERGYTHE PAULI PRINCIPLE KEEPS ELECTRONS WITH THE SAME SPIN SPATIALLYAPART.THIS PRINCIPLE APPLIES WHETHER ONE IS DEALING WITH ELECTRONS ONTHE SAME MOLECULE OR ON DIFFERENT MOLECULES AND IS THEPREDOMINANT REPULSIVE FORCE R IS THE DISTANCE BETWEEN MOLECULES OR NONBONDED ATOMS AND A IS A CONSTANT THAT DEPENDS ON THE ATOM TYPES. KEY POINT IS THAT THE REPULSIVE ENERGY RISES VERY QUICKLY ONCE THE ELECTRONS FROM TWO DIFFERENT ATOMS OVERLAP SIGNIFICANTLY
  13. 13. POLARIZATION ENERGYWHEN TWO MOLECULES APPROACH EACH OTHER, THERE IS CHARGEREDISTRIBUTION WITHIN EACH MOLECULE, LEADING TO AN ADDITIONALATTRACTION BETWEEN THE MOLECULES. THE ENERGY ASSOCIATED WITH THIS CHARGE REDISTRIBUTION ISINVARIABLY ATTRACTIVE AND IS CALLED THE POLARIZATION ENERGY.FOR EXAMPLE, IF A MOLECULE WITH POLARIZABILITY A IS PLACED IN ANELECTRIC FIELD.
  14. 14. POLARIZATION IS THE ADDITIVE PROPERTY THAT IS POLARISATION OF AMOLECULE IS EQUAL TO SUM TOTAL OF THE POLARISABILITY OF THE ATOMSIT IS ROUGHLY PROPORTIONAL TO THE NUMBER OF VALENCE ELECTRONSAS WELL AS ON HOW TIGHTLY THESE VALENCE ELECTRONS ARE BOUND TOTHE NUCLEI. UMEYAMA AND MOROKUMA HAVE CALCULATED THE ION-INDUCED DIPOLE CONTRIBUTION TO THE PROTON AFFINITIES OF THE SIMPLE ALKYL AMINES. NH 3 < CH3NH, < (CH3)2NH < (CH3)3N  THEY ATTRIBUTED THE ORDER OF GASPHASE PROTON AFFINITIES IN THE ALKYL AMINES TO THE GREATER POLARIZABILITY OF A METHYL GROUP THAN A HYDROGEN
  15. 15. CHARGE TRANSFER ENERGYWhen two molecules interact, there is often a small amount of electron flow fromone to the other.For example, in the equilibrium geometry of the linear water dimer HO-H. .OH2,the water molecule that is the proton acceptor has transferred about 0.05e- to theproton donor water .The attractive energy associated with this charge transfer is the charge transferenergy.Although the charge transfer energy is an important contributor to theinteraction energy of most noncovalent complexes IT does not mean that thecharge transfer energy is the predominant force holding the complex together in itsground state. For example, the complex between benzene and I,, earlier thought to be aprototype "charge transfer“ complex, seems to be held together predominantly Byelectrostatic, polarization, and dispersion energies in its ground electronic state
  16. 16. DISPERSION ATTRACTIONTHERE ARE ATTRACTIVE FORCES EXISTING BETWEEN ALL PAIRS OFATOMS, EVEN BETWEEN RARE GAS ATOMS (HE, AR, NE, KR, XE), WHICHCAUSE THEM TO CONDENSE AT A SUFFICIENTLY LOW TEMPERATURE. IT ISCALLED THE DISPERSION ATTRACTION.EVEN THOUGH THE RARE GAS ATOMS HAVE NO PERMANENT DIPOLEMOMENTS, THEY ARE POLARIZABLE, AND ONE HAS INSTANTANEOUS DIPOLE-DIPOLE ATTRACTIONS IN WHICH THE PRESENCE OF A LOCALLY ASYMMETRICCHARGE DISTRIBUTION ON ONE MOLECULE INDUCES AN ASYMMETRICCHARGE DISTRIBUTION ON THE OTHER MOLECULE, E.G., -HeΔ+ . . .- HeΔ+.THE NET ATTRACTION IS CALLED DISPERSION ATTRACTION IT DIES OFF AS1/R6, WHERE R IS THE ATOM-ATOM SEPARATION.
  17. 17. SUMMARYUNLIKE THE TOTAL INTERACTION ENERGY, WHICH CAN BE MEASUREDEXPERIMENTALLY, THE INDIVIDUAL ENERGY COMPONENTS CANNOT. RARE GAS-RARE GAS INTERACTIONS (He. . .He AND Xe. . .Xe) HAVE ONLYDISPERSION ATTRACTION.THE GREATER POLARIZABILITY OF THE XENON ATOMS, CAUSES THEGREATER DISPERSION ATTRACTION BETWEEN THEM A SIMPLE MANIFESTATION OF THIS IS THE MUCH HIGHER BOILINGPOINT OF XENON THAN HELIUM, CAUSED BY THE GREATER ATTRACTIVEFORCES IN XENON LIQUID.ALTHOUGH THESE ENERGIES ARE INDIVIDUALLY FAIRLY SMALL, THEY CANADD IN A MOLECULAR ENVIRONMENT TO SIGNIFICANT ENERGIES FOR EXAMPLE THE SINGLE LARGEST ATTRACTIVE FREE ENERGYCONTRIBUTION TO BINDING IN THE STRONGEST KNOWN SMALLMOLECULE-MACROMOLECULE INTERACTION (BIOTIN-AVIDIN) IS THEDISPERSION ATTRACTION
  18. 18. REFERENCES1 BURGERS “MEDICINAL CHEMISTRY AND DRUG DISCOVERY”, 5thEdition,vol-1 page no-170-1752 http://pubs.acs.org/doi/abs/10.1021/jp1030224 3 www.newworldencyclopedia.org/entry/Supramolecular_chemistry
  19. 19. THANkU

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