Chapter 9 Catalysis 9.1 General principles of catalysis Turnover number: the average number of reactants that a catalyst acts on before the catalyst loses its activity. The catalyst increases rate of reaction (decreases activation energy). The thermodynamics of a catalyzed reaction are unaffected by the catalyst. A heterogeneous catalyst: one that does not dissolve in the solution. Ex) Pd/C A homogeneous catalyst: one that dissolves in the solution. All calaysts operate by the same general principle – that is, the activation energy of the rds must be lowered in order for a rate enhancement to occur. 9.1.1 Binding the transition state better than the ground state Substrate: any material (reactant) used in a catalytic reaction Activated complex: simply referred to as the transition state Rate enhancement: the ratio of the rate constant for the catalyzed reaction to that for the uncatalyzed one. To achieve catalysis, the catalyst must stabilize the transition state more than it stabilizes the ground state. That is, the transition state must be bound better than the ground state. 1 2 9.1.3 A spatial temporal approach To achieve catalysis, the catalyst must stabilize the transition state more than it stabilizes the ground state. That is, the transition state must be bound better than the ground state. Another explanation for catalysis: spatial temporal postulate, many intramolecular reactions are often much faster than corresponding intermolecular reactions. -> the rate of reaction between functionalities A and B is proportional to the time that A and B reside within a critical distance. The longer that A and B spend together in the correct geometry for reaction, the greater that probability. When bound to the catalyst, the distance between A and B is closer than when they are free in solution, and inherently the transition state brings A and B close because bonds are beginning to form. In summary, binding is the key element in the most widely accepted theory of how catalysis is achieved. Greater binding of the transition state relative to the ground state is all that needs to be invoked to give a rate enhancement. 3 9.2 Forms of catalysis 9.2.2 Proximity as binding phenomenon Intermolecular aminolysis (k1; 1/M·s) 1.3 x 10-4 /M·s Intramolecular cyclization (k2; 1/s) 0.17/s -> a rate enhancement of 1200 Effective molarity (E.M.) or intramolecularity; ratio of the first order to second order rate constants for the analogous reactions. -> tell us the effective concentration of one of the components in the intramolecular reaction 4 Entropies of translation and rotation 5 Gem-dimethyl effect: sterically compress two groups together and preorganize two reactants in proximity close decrease of angle R R 6 Twisted amide 11 12 E.M. = 10 -10 -> very reactive Tetrahedral intermediate -> infinitely stable 7 9.2.3 Electrophilic catalysis Electrophilic catalysis includes simple electrostatics, hydrogen bonding, acid catalysis, and electrophilic metal coordination. Electrostatic interactions Oxyanion hole 8 150-fold rate enhancement Cation-π interactions 9 Metal ion catalysis 2 x 1016-fold rate enhancement pKa of metal-bound water = 7.2 (108 more acidic than water itself) 10 11 9.2.4 Acid-base catalysis; 9.3에서 설명 9.2.5 Nucleophilic catalysis Nucleophilic catalysis arise when a nucleophile binds to a reactant and enhances its rate of reaction. -> less common than electrostatic catalysis better electrophile and more reactive than the starting acid halide or anhydride NMe2 NMe2 N N H DMAP; N,N'-dimethylaminopyridine 12 9.2.6 Covalent catalysis Iminium ion enamine 13 14 9.2.7 Strain and distortion When a substrate binds to a catalyst that is more complementary in structure or electronic characeristics to the transition state, the substrate may distort in order to optimize binding interactions. That is, because the catalyst is designed to optimally bind the transition state, it necessarily is not optimal for the most stable structure of the ground state. -> distortion as a strain on the substrate -> the strain raises the energy of the substrate -> diminish activation energy 15 16 The chair is distorted into a conformation resembling a half-chair 9.3 Brønsted acid-base catalysis 9.3.1 specific catalysis The specific acid is defined as the protonated form of the solvent in which the reaction is being performed. + + + eg) H3O , CH3CNH , CH3SO(H )CH3 The specific base is defined as the conjugate base of the solvent. - - - eg) HO , CH2CN, CH3SOCH2 The specific acid catalysis refers to a process in which the reaction rate depends upon the specific acid, not upon other acids in the solution. The specific base catalysis refers to a process in which the reaction rate depends upon the specific base, not upon other bases in the solution. 17 + kobs = k[H3O ]/KaRH+ Specific acid catalyzed reactions added acid (AcOH in H2O) A-는 반응에 관여하지 않음. 따라서 rate law에 포함되지 않음 - + KaHA = [A ][H3O ]/[HA] + + KaRH+ = [R][H3O ]/[RH ] 앞과 동일 [HA] 항 없음 If the acid catalysis is involved in an equilibrium prior to the rds, and it is not involved in rds, then the kinetics of the reaction will depend solely upon the concentration of the specific acid. This is true even if an added acid (AcOH) is involved in protonating the reactant. Why? When a prior equilibrium is established, [RH+] determines the rate of the reaction. + + The concentration of RH depends solely upon the pH and the pKa of RH , and does not depend upon the concentration of the acid HA that was added to solution. 18 Specific base catalyzed reactions BH+는 반응에 관여하지 않음. 따라서 rate law에 포함되지 않음 - + KaRH =[R ][H3O ]/[RH] + kobs = kKaRH /[H3O ] [B] 항 없음 23 page에서 다시 설명 19 Kinetic plots The hallmark of specific acid or specific base catalysis is that the rate depends on the pH and not on the concentration of various acids or bases. This always means that an equilibrium involving the acid or base occur prior to rds, and the acid or base is not involved in rds itself. specific acid catalysis specific base catalysis k = k[H O+]/K + obs 3 aRH+ kobs = kKaRH /[H3O ] logkobs = logk–pH-logKaRH+ logkobs = logk+pH+logKaRH+ added acid added base 20 9.3.2 General catalysis In case that the proton transfer is involved in rds, not in a prior equilibrium -> general catalysis When an acid is involved in rds, -> general acid catalysis When a base is involved in rds, -> general base catalysis The term ‘general’ refers to the fact that any acid or base we added to the solution will affect the rate of the reaction. The term ‘specific’ refers to the fact that just one acid or base, that from the solvent, affects the rate of the reaction. General acid catalyzed reactions HA는 반응에 관여함. 따라서 rate law에포함 - + Ka = [A ][H3O ]/[HA] + - kobs = k[HA] or k[H3O ][A ]/Ka - Since the acid is always regenerated after the reaction, its concentration never changes over the course of the reaction -> pseudo-first order21 - the concentration of either HA or A- is in the rate expression. General base catalyzed reactions B는 반응에 관여함. 따라서 rate law에포함 - + kobs = k[B] or k[HO ][HB ]/Kb - Since the base is always regenerated after the reaction, its concentration never changes over the course of the reaction -> pseudo-first order - the concentration of either B or BH+ is in the rate expression. 22 19 page slow 실제로는 첫번째 단계가 rds 따라서 HO-는 general base로작용 Note: ‘specific’ is used to designate the protonated or deprotonated form of the solvent + (H3O or HO- for water), but it is also used to designate a mechanism involving an acid or base in an equilibrium prior to rds. However, sometimes hydronium or hydroxide can be involved in rds. In this case the specific acid and base are participating in general-catalysis. 23 Kinetic plots The hallmark of specific acid or specific base catalysis is that the rate depends on the pH and not on the concentration of various acids or bases. This always means that an equilibrium involving the acid or base occur prior to rds, and the acid or base is not involved in rds itself. general acid catalysis general base catalysis + - - + kobs = k[HA] or k[H3O ][A ]/Ka kobs = k[B] or k[HO ][HB ]/Kb 페이지 20과비교 pH < pKa, HA로주로존재, 따라서 k의변화없음 - pH ~ pKa, HA와 A (이것은 반응에 관여하지 않음)이공존 - pH > pKa, HA가 점차적으로 A 로 바뀌어 k가 지속적으로 감소 C와 mirror image general acid catalysis general base catalysis 24 9.3.4 Concerted or sequential general-acid-general-base catalysis Both a general acid and a general base catalyst are required for a reaction. This is often the case with enzymes. acid base kobs = k[HA][B] The rate dependence on pH is a combination of that observed for general-acid and general-base catalyst. The largest kobs is found at pH where the product of the concentrations of HA and B is at a maximum 25 9.4 Enzymatic catalysis physical process 9.4.1 Michaelis-Menten kinetics chemical process k1 kcat E + S ←→ E·S → P + E E·S: Michaelis complex k-1 E + S ←→ → P E·S rate = d[P]/dt = kcat[ES] d[ES]/dt = k1[E][S] – k-1[ES] - kcat[ES] = 0 [E]0 = [E] + [ES] [E] = [E]0 -[ES] k1([E]0-[ES])[S] – k-1[ES] - kcat[ES] = 0 [E] [S] [ES] = 0 Km = (k-1 + kcat)/k1 Km + [S] k [E] [S] cat 0 Michaelis-Menten equation rate = d[P]/dt = kcat[ES] = Km + [S] 26 Kinetic parameters to be determined for enzymatic reactions: kcat and Km 9.4.2 The meaning of Km, kcat and kcat/Km 1.