STUDIES ON SOME REACTIONS PROMOTED BY THE COMPLEXES OF TRANSITION METALS WITH POLYAZAMACROCYCLES

Abstract

The problem of enzyme mechanism is of fundamental importance because enzymes are the most efficient known catalysts. Anumber of enzymes require a metal ion for their activity. Due to the complexity of enzyme structures, it is often more informative to carry out studies with model compounds, which have active structural features similar to the enzymes. As a result, a large number ofstudies have been carried out on determining the mechanism of hydrolysis of avariety of organic substrates and also on the effect of metal ions on some of these reactions. Keeping in view the work already done in this wide field, I have carried out hydrolytic studies on two systems. In the first system, I have studied the intramolecular catalyzed hydrolysis of carbonate esters and the influence on these reactions of an OH" ion coordinated to macrocyclic complexes, and the results of this work are presented in Chapter I. In the second system, I have investigated the hydrolysis of some novel amides and the catalysis of these reactions by metal ions and macrocyclic complexes, and the results of these studies are presented in Chapter II. Chapter I In this chapter, I have studied the hydrolysis of 4-nitrophenyl-2- benzamido carbonate (II). The hydrolysis of 4-nitrophenyl-4-benzamido carbonate (III) and 4-nitrophenyl acetate has also been studied for comparative purposes. The hydrolysis of (II) can be depicted as proce eding either through oxygen or nitrogen intramolecular attack. In contrast, the hydrolysis of (III) proceeds through normal H20 or OH" attack. The hydrolysis of (II) proceeds about 900 times faster than that of (III). The log kobs vs pH profile for the hydrolysis of (II) is similar to the ones reported earlier for the hydrolysis of similar compounds. Thus this reaction should also involve an intramolecular attack proceeding through an initial cyclization process. This has been confirmed by isolation of the cyclic intermediate as well as the final product, salicylamide. The product analysis studies also show that the initial cyclization occurs through an intramolecular attack by nitrogen of the adjacent amide group. The pH independent reaction can be unimolecular breakdown of the compound or 3 it may involve a water reaction. The log kobs vs pH profile can be mathematically represented as: kobs "" ^1 + an where kx is the plateau rate at low pH, k2 is the second order rate constant at higher pH. The macrocyclic complex, [CoL(NCS)(OH)]+ promoted hydrolysis of 4-nitrophenyl acetate, (II), and (III) has been studied at 25°C at I = 0.1 Mat pH 9.0, 6.20 and 8.95 respectively. In all these reactions the ester concentration was 1.84 x 10"4 M and the metal complex was present in at least 10 fold excess. For [CoL(NCS)(OH)]+, L = cyclam, Me6[14]diene, or Me2Et4[14]diene. The results of these hydrolytic studies show excellent first order dependence on ester concentration. The rate expression for the metal complex catalyzed reactions can be written as: kobs = ko + kN[complex] where k0 is the rate ofhydrolysis in absence of the complex and kN is the rate constant for the hydrolysis corresponding to the metal complex bound 4 OH" catalysis. The hydrolysis of 4-nitrophenyl acetate occurring through nucleophilic catalysis can be represented as: O O" II k, I RO"+ CH3 - C - OAr ;= = = = - RO - C - OAr K I CH3 I CH3 - C - OR + ArO" II O The pKa values of the macrocyclic complexes used in these studies lie in the range of 5.8 to 6.0, which are lower than the pKa of 7.14 for 4-nitrophenol. Therefore, in these reactions, the first step involving the nucleophilic attack of the metal bound hydroxide on the substrate, corresponding to kx is the rate determining step. The Bronsted type plot of log k vs pKa of the conjugate acid nucleophile shows levelling beyond pKa of about 10 and an initial slope of B = 0.3. The rates for the macrocyclic complex catalyzed reaction lie on the initial part of this curve. The present macrocyclic complexes give about 40 times rate enhancement over [Co(NH3)5(OH)]2+. On the basis of these results, 5 a general conclusion can be drawn that oxygen nucleophiles on metal clusters will have a nucleophilicity which broadly equates with their basicity. Chapter II In this chapter, I have studied the hydrolysis of an amide carrying a very effective chelating group and the effect of divalent metal ions, and their macrocyclic complexes on its rate of hydrolysis. The hydrolysis of N-picolinoyl benzimidazole (A) has been studied earlier and the reaction kinetics shown to follow the general rate expression: k2.aH2 + k0.k2.aH + k0H.Kw.K2 kobs = aH2 + K2.aH where k^ is the second order rate constant for the OH" catalyzed reaction and k0 is the rate constant for the reaction ofthe mono protonated species and Kx and K2 are the first and second dissociation constants of the sub strate. The hydrolysis of N-l,10-phenanthrolinoyl benzimidazole (B) shows a similar behavior to that of (A). A similar behavior is expected for the hydrolysis of N-l,10-phenanthrolinoyl imidazole (C), which could not be studied due to the reaction being very fast. The hydrolysis profile

of (B) shows hydronium ion, hydroxide ion and water catalyzed reactions. The water reaction in the pH range 4.5 to 7.5 is more facile for (B) than reported so far and for (C) it is still higher. The value of k0 is over 9-fold higher for (B) and 20-fold higher for (C) as compared to (A), which is about 4-fold higher than that for N-benzoylimidazole. The high rate of hydrolysis of (B) and (C) is due to an electronic influence of the phenanthroline group and does not involve any participation ofthis group in an intramolecular reaction. The pH independent reaction in (B) is very likely to proceed with water catalysis of the hydrolysis of the neutral species as suggested earlier for N-acetylimidazole. The effect of metal ions Cu2+, Ni2+, Co2+ and Zn2+ on the hydrolysis of (A) has been studied earlier. These ions show very large rate enhancements which occur by virtue ofthese metal ions coordinating to the substrate. The largest rate enhancement was observed with Cu2+. In these reactions hydrolysis could occur either through an intramolecular attack- of a metal ion bound OH" or attack of an external OH" ion on the metal ion coordinated substrate. The rate enhancements are also observed in the hydrolysis of (B) by Cu2+, Ni2+, Co2+ and Zn2+. These ions can

coordinate strongly with the phenanthroline group and hence show much larger rate enhancements as compared to those in (A). The hydrolysis of (B) would proceed in the same way as that of (A). The rate enhancements noted for (B) are the largest effects observed so far for any amide hydrolysis. The value of rate constant for these metal ion promoted reactions exceed that of a rate constant for a diffusion controlled reaction (10 M"1 s"1). Thus, the reactions studied here must involve intramolecular attack of a metal ion coordinated OH" ion. The nucleophilic attack of OH" is the likely rate determining step and the strength of binding of the metal to the substrate should a be decisive factor in determining the final rate of hydrolysis. The hydrolysis scheme can be summarized as: ,. *f , KM0H M2+ + S F====- [NiS]2+ - ====- [M(OH)(S)]+ + H+ kd . products This gives the rate expression: kA-KMontM2*] kobs aH(kd + MM"]) + K^mH% + kf[M2+]) 8 The hydrolysis of (A) and (B) has also been studied in presence of macrocyclic complexes of Ni2+ and Cu2+. These complexes have a square planar geometry and can bind to the substrate through the two vacant coordination sites. However, after coordination to the substrate they cannot bind an OH" ion, which may be required for an intramolecular attack. The hydrolysis profile for (A) is now similar to the one observed in absence of any catalyzing species. This supports the postulation for an intramolecular attack by a metal ion coordinated OH" ion. The low rate enhancements also show that the rate determining step is the rate of binding of the catalyst to the substrate. This conclusion is based on the fact that the hydrolysis rate is different in presence of various macrocyclic complexes. The rate of formation of Cu2+ complexes is known to be faster than that ofNi2+ complexes. The hydrolysis is faster in presence of the Cu2+ complexes as compared to the rate in presence of the Ni2+ complexes. The ease of formation of these substrate - macrocyclic complex adducts is also influenced by the ease with which the macrocycle can fold. Folding of the macrocycle is required to expose two cis sites on the metal to enable coordination with the substrate. The rate ofhydrolysis

is faster with those complexes which have a more facile folding ability.