Ascorbic Acid - American Chemical Society

7 Chelates of Ascorbic A c i d Formation and Catalytic

Properties

ARTHUR E. MARTELL

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Department of Chemistry, Texas A&M University, College Station, TX 77843

Ascorbic acid, H L, is a relatively weak bidentate ligand, which coordinates metal ions, M , to form chelates, MHL at low and intermediate p H values, and unprotonated chelates, ML at high pH. Metal ions capable of undergoing redox reactions catalyze the autoxidation of ascorbic acid through the formation of intermediate metal 2

n+

+n-1

+n-2

-ascorbate-dioxygen complexes. Catalysis of autoxidation by metal chelates seems to occur through the formation of ternary ascorbate complexes of the metal chelates. Ascorbic acid is assigned a significant catalytic role in Udenfriend's system through the formation of an initial ascorbateFe(III)-dioxygen complex in which electron transfer to dioxygen results in oxygen activation and oxygen atom insertion.

Ascorbic acid, 1, is a dibasic acid with a bifunctional ene-diol group built into a heterocyclic lactone ring (1). Although the dissociation constants of the ene-diol hydroxyls are increased somewhat over normal values by the electron-withdrawing oxygen atoms on the adjacent 1- and 4-positions, the acidity of ascorbic acid is due mainly to resonance stabilization of the monoanion (2), which distributes the negative charge between the oxygens at the 1- and 3-positions, as indicated by 2a and 2a'. Such stabilization is not possible when the 3-hydroxyl is not ionized. Formula 2b therefore represents a higher energy form that does not contribute appreciably to the structure of the monoanion. The undissociated hydroxyl group of the monoanion may be hydrogen bonded to either of the adjacent negatively charged oxygens at the 1- and 3-posi tions, as indicated by 2a and 2a'. The high acidity of the 3-hydroxyl group can be readily understood by analogy with carbonic acid mono esters, with which it has a vinylogous relationship. The nature of the monoanion has been well-characterized by x-ray crystallographic studies 0065-2393/82/0200-0153$06.00/0 © 1982 American Chemical Society In Ascorbic Acid: Chemistry, Metabolism, and Uses; Seib, P., et al.; Advances in Chemistry; American Chemical Society: Washington, DC, 1982.

154

ASCORBIC ACID

of its salts (2,4) a n d its m e t a l complexes

(3,5) as w e l l as b y I R (6)

a n d N M R ( 7 ) studies o f t h e l i g a n d a n d its m e t a l complexes. T h e s e c o n d p K c o r r e s p o n d i n g t o t h e c o n v e r s i o n o f 2a t o 3 i s r e l a t i v e l y h i g h ( ~ 11.3) because o f t h e n e g a t i v e c h a r g e o n 2a, a n d h y d r o g e n b o n d i n g t o t h e n e g a t i v e oxygens at t h e 1- a n d 3-positions. B o t h effects t e n d to increase t h e s t a b i l i t y o f t h e m o n o a n i o n r e l a t i v e t o t h e c o m pletely dissociated form. T h e b i n e g a t i v e e n e - d i o l a n i o n o f a s c o r b i c a c i d , L " , is a b i d e n t a t e 2

l i g a n d a n d is c a p a b l e o f r e a c t i n g w i t h m e t a l ions M * o f c o o r d i n a t i o n n

n u m b e r 4 o r 6 t o f o r m a series o f complexes M L * " " , M L " " ; o r M L * " " , Downloaded by UNIV OF GUELPH LIBRARY on June 5, 2012 | http://pubs.acs.org Publication Date: June 1, 1982 | doi: 10.1021/ba-1982-0200.ch007

2

2

+

4

2

M L * ~ , a n d M L * " ; respectively. C o m p a r i s o n w i t h analogous ligands n

2

4

n

3

6

h a v i n g s i m i l a r p K ' s i n d i c a t e s t h a t t h e stabilities o f t h e 1:1

ascorbate

chelates o f d i v a l e n t t r a n s i t i o n metals s h o u l d b e i n t h e r a n g e o f 10 -10 . 5

10

T h e s t a b i l i t y constant d a t a a v a i l a b l e f o r a s c o r b i c a c i d , l i s t e d i n T a b l e I , i n d i c a t e that o n l y r e l a t i v e l y v e r y w e a k chelates h a v e b e e n r e p o r t e d . F o r t h e " n o r m a l , " f u l l y d e p r o t o n a t e d chelates, t h e stabilities o f o n l y t h e 1:1 chelates o f C a ( I I ) , F e ( I I ) , C d ( I I ) , a n d A g ( I ) a r e i n d i c a t e d . T h e f o r m a t i o n constants l i s t e d a r e i n t h e r a n g e o f 10

M

t o 10 - , orders o f 3 6

m a g n i t u d e b e l o w w h a t w o u l d b e expected f o r complexes

of the type

i n d i c a t e d b y f o r m u l a 5. Table I.

Stabilities of Metal Chelates of L-Ascorbic A c i d ( H L ) 2

Metal Ion

Equilibrium

Log Formation Constant (p. = 0.10M;t = 25 C)

Quotient

HL-]/[H*][L ] H L]/[H1[HL"] CaHI/]/[Ca 1[HI/] CaL]/[Ca *][L -] SrHL*]/[Sr *] [HL"] MnHI/]/[Mn *][HL-] F e H I / J / t F e * ] [HL~] FeL]/[Fe ][L "] NiHL ]/[Ni ][HL-] CuHL ]/[Cu ][HL"] ZnHI/]/[Zn *][HL-] CdHI/]/[Cd ][HL-] PbHI/]/[Pb ][HI/] AlHL ]/[AP][HL"] A1(HL) *][AP][HL-] ;AgL-]/[Ag*][L -] U0 HI/]/[U0 ][HL-] U0 (HL) ]/[U0 ][HL-]

o

11.34 4.03 0.2

2

H Ca * +

2

2

a

2

2

Sr * Mn Fe * 2

2

0. 3 1. r 0.21'

2 t

2

2

2

2 +

N P Cu Zn Cd * Pb * A P

+

2 t

:

2 t

2

2 +

+

2 t

2

2

:

2

2 t

2 t

:

2 t

2

2

2

2

2

2

2

2 +

2

2 t

2

i.r 1.6 1.0° 0.42' 1.8 1.9 3.6 3.66 2.35 3.32

• 2 5 ° C , / B = 0.16 M. »25°C,/t = 3 . 0 M . •25 C u~0. O

1.4'

a

2

( /

Source: Reference 1.

In Ascorbic Acid: Chemistry, Metabolism, and Uses; Seib, P., et al.; Advances in Chemistry; American Chemical Society: Washington, DC, 1982.

2.0'

Chelates of Ascorbic Acid


MARTELL

5b


156

ASCORBIC

ACID

M o s t of the m e t a l chelates for w h i c h s t a b i l i t y constants h a v e b e e n r e p o r t e d are t h e 1:1 m o n o p r o t o n a t e d chelates c o r r e s p o n d i n g to f o r m u l a 4.

T h e s e are q u i t e w e a k , w i t h l o g K values r a n g i n g f r o m

0.2-2.35,

b e c a u s e of the l o w n e g a t i v e c h a r g e o n the l i g a n d a n i o n a n d t h e fact t h a t one of t h e t w o d o n o r oxygens is p r o t o n a t e d . O f t h e p o s s i b l e l i g a n d donor

group

arrangements indicated b y

formulas 4 a and 4b, 4a

is

g e n e r a l l y a c c e p t e d a n d agrees w i t h the x - r a y d a t a t h u s far o b t a i n e d f o r this t y p e of chelate c o m p o u n d .

T h e b o n d i n g arrangement i n 4b, h o w

ever, is s t i l l a reasonable p o s s i b i l i t y because of

the d e r e a l i z a t i o n of


n e g a t i v e c h a r g e b e t w e e n t h e oxygens at the 1- a n d 3-positions. A l t h o u g h the m e t a l chelates of t h e c o m p l e t e l y d e p r o t o n a t e d l i g a n d are g e n e r a l l y w r i t t e n as i n d i c a t e d b y 5 a, there is also a p o s s i b i l i t y of t h e f o r m a t i o n of c o o r d i n a t e b o n d i n g m o d e s of the t y p e i l l u s t r a t e d b y 5 b, a g a i n because o f t h e d e r e a l i z a t i o n of

negative charge

between

the

oxygens b o u n d to t h e 1- a n d 3 - c a r b o n atoms. T h e l a c k of d a t a i n t h e l i t e r a t u r e o n the " n o r m a l " m e t a l chelates i n w h i c h t h e l i g a n d is f u l l y d e p r o t o n a t e d is p r o b a b l y d u e to the f a c t that f o r m o s t m e t a l ions s u c h chelates are f o r m e d o n l y i n a l k a l i n e s o l u t i o n . I n t e r e s t i n g r e d o x reactions of

a s c o r b i c a c i d , its salts, a n d its m e t a l chelates take p l a c e i n a c i d

s o l u t i o n a n d m a y b e c o n v e n i e n t l y s t u d i e d at m o d e r a t e l y l o w to l o w p H . I n a l k a l i n e s o l u t i o n the rate of a u t o x i d a t i o n of a s c o r b i c a c i d a n d t h e effect of trace i m p u r i t i e s that c a t a l y z e s u c h o x i d a t i o n reactions increase m a n y f o l d , a n d t h e p r e c a u t i o n s necessary to c a r r y out

studies i n a l k a l i n e

s o l u t i o n are s o m e w h a t i n c o n v e n i e n t . T h e r e seems to be no f u n d a m e n t a l reason, h o w e v e r ,

w h y chelate f o r m a t i o n b y a s c o r b i c a c i d w i t h

non-

o x i d i z i n g m e t a l ions c o u l d not be s t u d i e d at m o d e r a t e l y to h i g h p H u n d e r s u c h c o n d i t i o n s that the m e t a l ions d o not h y d r o l y z e extensively or p r e c i p i t a t e .

Oxidation by Metal Ions and Metal Chelates A s c o r b i c a c i d is a s t r o n g t w o - e l e c t r o n r e d u c i n g agent t h a t is r e a d i l y o x i d i z e d i n one-electron steps b y m e t a l ions a n d m e t a l complexes i n t h e i r h i g h e r v a l e n c e states. A n i n n e r sphere m e c h a n i s m for t h e s t o i c h i o m e t r i c o x i d a t i o n of a s c o r b i c a c i d b y f e r r i c i o n i n a c i d s o l u t i o n is i l l u s t r a t e d b y Scheme 1 ( 8 ) .

T h e first step i n the r e a c t i o n is the f o r m a t i o n of a m o n o

protonated F e ( I I I )

c o m p l e x s i m i l a r to t h e m o n o p r o t o n a t e d

ascorbate

complexes l i s t e d i n T a b l e I. T h e i n t e r m e d i a t e m o n o p r o t o n a t e d c o m p l e x is s h o r t - l i v e d a n d r a p i d l y u n d e r g o e s

Fe(III)

a n i n t r a m o l e c u l a r one-

e l e c t r o n transfer to g i v e a d e p r o t o n a t e d F e ( I I ) c o m p l e x of t h e ascorbate r a d i c a l a n i o n , i n d i c a t e d b y 7. T h i s c o m p l e x dissociates to the free r a d i c a l a n i o n , w h i c h m a y t h e n c o m b i n e w i t h a s e c o n d f e r r i c i o n to f o r m t h e c o m p l e x 9. C o m p l e x 9 i n t u r n undergoes a s e c o n d i n t r a m o l e c u l a r e l e c t r o n



7.

MARTELL

157


6

Scheme 1.

7

Direct oxidation of ascorbic acid by ferric ion.

transfer to g i v e t h e final p r o d u c t , d e h y d r o a s c o r b i c a c i d , f o r m u l a 10. T h e m o n o p r o t o n a t e d c o m p l e x 6 has b e e n i d e n t i f i e d as t h e s t a r t i n g m a t e r i a l for b o t h C u ( I I ) - a n d F e ( I I I ) - c a t a l y z e d o x i d a t i o n of a s c o r b i c a c i d o n t h e basis of t h e p H d e p e n d e n c e of t h e r e a c t i o n rate f o r o x i d a t i o n w i t h b o t h m e t a l ions, a n d b y r a p i d e q u i l i b r i u m m e a s u r e m e n t s of

chelate

f o r m a t i o n w i t h C u ( I I ) i o n . T h e p o s t u l a t i o n i n S c h e m e 1 t h a t ascorbate r a d i c a l a n i o n 8, a n d its F e ( I I ) c h e l a t e 7, as w e l l as its F e ( I I I ) chelate 9, are c o m p l e t e l y d e p r o t o n a t e d , is b a s e d o n C h a p t e r 4 i n this v o l u m e . T h e o x i d a t i o n of a s c o r b i c a c i d b y C u ( I I ) i o n is s o m e w h a t less r a p i d t h a n t h e rate of o x i d a t i o n b y F e ( I I I ) , b u t is c o n s i d e r e d to p r o c e e d b y t h e same t y p e of m e c h a n i s m . A s m a y b e seen f r o m t h a t d a t a i n T a b l e I , t h e m o n o p r o t o n a t e d m e t a l chelates of a s c o r b i c a c i d are g e n e r a l l y q u i t e w e a k a n d t e n d to b e extensively d i s s o c i a t e d i n s o l u t i o n . M o r e o v e r , as electrons are w i t h d r a w n f r o m t h e l i g a n d to g i v e first t h e r a d i c a l a n i o n a n d

finally

t h e n e u t r a l d e h y d r o a s c o r b i c a c i d , t h e affinities of these o x i d i z e d f o r m s f o r m e t a l ions are f u r t h e r d e c r e a s e d w i t h e a c h o x i d a t i o n step. T h e r e f o r e ,


158

ASCORBIC ACID

w i t h the possible

exception

of

6, the m e t a l complexes

illustrated i n

S c h e m e 1 m a y represent r a t h e r m i n o r species i n the r e a c t i o n m i x t u r e . T h e m e c h a n i s m of o x i d a t i o n of ascorbic a c i d b y v a r i o u s m e t a l c h e lates s u c h as those of F e ( I I I ) a n d C u ( I I ) is s i m i l a r to the m e c h a n i s m of o x i d a t i o n b y the m e t a l i o n , except that the rates are v e r y m u c h l o w e r (9).

T h e s e reactions are also first o r d e r i n the ascorbate

and

first

o r d e r i n m e t a l chelate.

monoanion

T h e rates decrease r a p i d l y as

the

stabilities of the m e t a l chelates increase b u t do not correlate w i t h the rates

that w o u l d

be

predicted

through a mechanism

i n v o l v i n g the


e q u i l i b r i u m d i s s o c i a t i o n of the m e t a l chelate to the free ( a q u o ) m e t a l i o n . T h e r e f o r e , the reactions are b e l i e v e d to o c c u r t h r o u g h the f o r m a t i o n of a m i x e d l i g a n d chelate i n v o l v i n g ascorbate a n i o n as a secondary l i g a n d , a n d the r a t e - d e t e r m i n i n g e l e c t r o n transfer w o u l d be d e p e n d e n t not o n l y o n the s t a b i l i t y (i.e., the o x i d a t i o n p o t e n t i a l ) of t h e m e t a l chelate itself b u t also on steric factors r e l a t e d to the o r i e n t a t i o n a n d d i m e n s i o n s of the l i g a n d d o n o r groups. T h e s t o i c h i o m e t r i c r e d o x reactions of ascorbic a c i d w i t h o x i d i z i n g m e t a l ions a n d m e t a l chelates, of t h e t y p e i l l u s t r a t e d i n S c h e m e 1, are also i n v o l v e d i n the m e c h a n i s m s of o x i d a t i o n of ascorbic a c i d b y v a r i o u s oxidants since t h e y f u n c t i o n as v e r y efficient catalysts for s u c h reactions. F u r t h e r details c o n c e r n i n g electron transfer processes i n t h e m e t a l che lates of ascorbic a c i d w i l l be p r e s e n t e d i n the f o l l o w i n g discussion of the role of s i m p l e m e t a l ascorbate chelates a n d of m i x e d l i g a n d ascorbate chelates i n the o x i d a t i o n of a s c o r b i c a c i d b y m o l e c u l a r oxygen.

Catalysis of the Autoxidation of Ascorbic Acid by Metal Ions and Metal Chelates T h e systems d e s c r i b e d a b o v e b y w h i c h m e t a l ions a n d m e t a l chelates a c c o m p l i s h t w o - e l e c t r o n o x i d a t i o n of ascorbic a c i d , m a y b e e m p l o y e d i n c a t a l y t i c systems i n w h i c h the m e t a l i o n or chelate is o n l y a m i n o r c o n stituent.

A n y o x i d i z i n g agent c a p a b l e of r e o x i d i z i n g the m e t a l i o n or

chelate f r o m its l o w e r v a l e n t state to its h i g h e r v a l e n t state m a y employed.

be

W h i l e i n the f o l l o w i n g t r e a t m e n t the o x i d a n t is m o l e c u l a r

o x y g e n , it s h o u l d b e possible to set u p analogous r e a c t i o n systems w i t h other oxidants s u c h as h y d r o g e n p e r o x i d e , halogens, n i t r i t e i o n , a n d m a n y others. Metal-Ion-Catalyzed Autoxidation.

F i g u r e 1 illustrates the v a r i a

t i o n of the first-order rate constants for the a u t o x i d a t i o n of a s c o r b i c a c i d b y m o l e c u l a r o x y g e n w i t h the c o n c e n t r a t i o n of t h e C u ( I I ) i o n , w h i c h is present i n c a t a l y t i c (i.e. l o w ) concentrations ( 8 ) . indicates second-order order i n C u ( I I ) ] .

T h e linear relationship

b e h a v i o r [first o r d e r i n a s c o r b i c a c i d a n d

first

T h e c a t a l y t i c effect of C u ( I I ) is also seen to decrease



7.

MARTELL

159


in O «— X

2

4

6

8

10

12

[Cu(ll)] X 105 Figure 1. Rate constants for the Cu(H)-ion-catalyzed autoxidation of ascorbic acid as a function of Cu(H) concentration at —log [H ] values of: A , 1.50; B, 2.00; C , 2.25; D, 2.50; E, 2.85; and F , 3.45; t = 25°C; fi = 0.10M (KN0 ). +

3

r a p i d l y as h y d r o g e n i o n c o n c e n t r a t i o n is i n c r e a s e d . T h i s v a r i a t i o n of the second-order rate constant w i t h p H m a y b e e l i m i n a t e d i f the c o n c e n t r a t i o n of the substrate is r e p l a c e d b y t h a t of the m o n o a n i o n , i n d i c a t i n g t h a t t h e latter, or the c o r r e s p o n d i n g m o n o p r o t o n a t e d C u ( I I ) chelate, is t h e r e a c t i v e species i n t h e o x i d a t i o n r e a c t i o n .


160

ASCORBIC

ACID

A s i m i l a r c a t a l y t i c effect ( 8 ) of F e ( I I I ) o n t h e o x i d a t i o n of ascorbic a c i d is i l l u s t r a t e d i n F i g u r e 2. I n this case the o b s e r v e d rates are c o n s i d e r a b l y h i g h e r t h a n those i l l u s t r a t e d i n F i g u r e 1 for C u ( I I ) catalysis. T h e pseudo

first-order

r a t e constants f o r t h e o x i d a t i o n of ascorbic a c i d

i l l u s t r a t e d i n F i g u r e 2 are seen to v a r y i n a l i n e a r f a s h i o n w i t h

the

c o n c e n t r a t i o n of F e ( I I I ) , w h i c h is present i n c a t a l y t i c a m o u n t s .

The

rates i n d i c a t e d i n F i g u r e 2 are also seen to increase w i t h h y d r o g e n i o n c o n c e n t r a t i o n , a n d here a g a i n the p H v a r i a t i o n i n the rate i n d i c a t e s t h a t the m o n o a n i o n , or its m o n o p r o t o n a t e d

i r o n chelate, is f o r m e d i n a p r e -


e q u i l i b r i u m step p r i o r to t h e r a t e - d e t e r m i n i n g electron transfer r e a c t i o n . F r o m the d a t a i l l u s t r a t e d i n F i g u r e 2, second-order the F e ( I I I ) - c a t a l y z e d

o x i d a t i o n of the a s c o r b i c

rate constants

acid monoanion

for may

be c a l c u l a t e d . T h e second-order rate constants for t h e a u t o x i d a t i o n of ascorbic a c i d d e t e r m i n e d f r o m d a t a of the t y p e i l l u s t r a t e d i n F i g u r e s 1 a n d 2 f o u n d to be p r o p o r t i o n a l to the d i o x y g e n c o n c e n t r a t i o n .

At low

were

oxygen

concentrations this d e p e n d e n c e o n o x y g e n c o n c e n t r a t i o n w a s f o u n d

to

l e v e l off i n d i c a t i n g a change i n r e a c t i o n m e c h a n i s m . A l s o the rates i n the presence of o x y g e n w e r e f o u n d to be m u c h m o r e r a p i d t h a n the d i r e c t s t o i c h i o m e t r i c rates of o x i d a t i o n b y t h e C u ( I I ) a n d F e ( I I I ) ions i n t h e absence of m o l e c u l a r o x y g e n .

F i g u r e 3 illustrates the d e p e n d e n c e o n

o x y g e n c o n c e n t r a t i o n of the specific rate constants

(i.e., rate constants

b a s e d o n c o n c e n t r a t i o n of the m o n o p r o t o n a t e d a n i o n ) f o r the a u t o x i d a t i o n of ascorbic a c i d i n the presence of c a t a l y t i c amounts of F e ( I I I ) . r e l a t i o n s h i p s w e r e o b t a i n e d for C u ( I I ) i n d i c a t e t h i r d - o r d e r b e h a v i o r for C u ( I I )

catalysis.

T h e data

and Fe(III)

Similar therefore

catalysis of

the

a u t o x i d a t i o n of a s c o r b i c a c i d — f i r s t o r d e r i n substrate, first o r d e r i n m e t a l i o n , a n d over a l i m i t e d r a n g e of c o n c e n t r a t i o n , first o r d e r i n d i o x y g e n concentration.

T h i s b e h a v i o r , together w i t h the fact t h a t the

r e a c t i o n is m u c h m o r e r a p i d i n t h e presence

observed

of d i o x y g e n t h a n i n its

absence, p r o v i d e s e v i d e n c e for the f o r m a t i o n of a n i n t e r m e d i a t e ascorbate-copper-dioxygen

complex

transfer takes

The

place.

i n w h i c h t h e r a t e - d e t e r m i n i n g electron

experimental observation

that the

metal-

c a t a l y z e d o x i d a t i o n b y m o l e c u l a r o x y g e n is m u c h m o r e r a p i d t h a n the s t o i c h i o m e t r i c o x i d a t i o n of ascorbic a c i d b y the m e t a l i o n or chelate i n the absence of m o l e c u l a r o x y g e n , w a s n o t e d some t i m e ago b y D e k k e r and D i c k i n s o n (10)

b u t this o b s e r v a t i o n w a s i n t e r p r e t e d i n terms of the

r e a c t i v i t y of the ascorbate r a d i c a l a n i o n , a n d its i n v o l v e m e n t i n a free radical chain reaction. A r e a c t i o n m e c h a n i s m f o r the m e t a l - i o n - c a t a l y z e d a u t o x i d a t i o n of a s c o r b i c a c i d , i n v o l v i n g the f o r m a t i o n of a n i n t e r m e d i a t e t e r n a r y ascorb a t e - m e t a l i o n - d i o x y g e n c o m p l e x , is i l l u s t r a t e d i n S c h e m e 2.

Although

the b o n d i n g b e t w e e n the m e t a l i o n a n d the d i o x y g e n i n t h e i n t e r m e d i a t e



161


MARTELL

I

I

I

I

I

I

0

2

4

6

8

10

I— 12

[Fe (III)] x 105 Figure 2. Rate constants for the Fe(III)'ion~catalyzed autoxidation of ascorbic acid as a function of Fe(III) concentration at —log [H*] values of: A , 1.50; B, 2.00; C , 2.42; D, 2.94; E, 3.44; t = 2S°C; p. = 0 . I 0 M (KNO ). s


162

ASCORBIC

ACID


3.0

0

[ 0 ] X 1(H 2

Figure 3. Variation of second-order rate constants for the Fe(HI) catalyzed autoxidation of ascorbic acid as a function of oxygen concentration at -log [H ] values of: A, 3.85; B, 3.45; C, 3.00; t = 25°C; /x = 0.10M (KNO ). +

s


MARTELL



7.


163

164

ASCORBIC

ACID

d i o x y g e n c o m p l e x w o u l d seem to b e e x t r e m e l y w e a k , i t m a y b e s t a b i l i z e d b y resonance

of the t y p e i n d i c a t e d b y

suggested b y H a m i l t o n ( I I ) .

11a a n d l i b

(Scheme 2)

as

T h e r a t e - d e t e r m i n i n g e l e c t r o n transfer step

i l l u s t r a t e d i n S c h e m e 2 is i n d i c a t e d as o c c u r r i n g t h r o u g h a n i o n i c shift of t w o electrons i n a c c o r d a n c e w i t h the suggestion of H a m i l t o n ( I I )

to

give directly a C u ( I I ) complex containing w e a k l y coordinated dehydro a s c o r b i c a c i d a n d a m o r e s t r o n g l y c o o r d i n a t e d h y d r o p e r o x i d e d o n o r , as i n d i c a t e d b y f o r m u l a 12.

T h i s c o m p l e x r a p i d l y dissociates to t h e free

m e t a l i o n , h y d r o g e n p e r o x i d e , a n d the o x i d a t i o n p r o d u c t .

W h i l e the


r e d o x r e a c t i o n i n v o l v i n g transfer of t w o electrons is i l l u s t r a t e d i n the m e c h a n i s m i n S c h e m e 2 as o c c u r r i n g i n a single step, i t w o u l d also b e q u i t e reasonable to i l l u s t r a t e the r e d o x r e a c t i o n as o c c u r r i n g i n t w o successive one-electron transfers w i t h the f o r m a t i o n of a n i n t e r m e d i a t e c o m p l e x i n w h i c h C u ( I I ) is b o u n d to a d e p r o t o n a t e d ascorbate r a d i c a l anion and a superperoxide anion. W i t h kinetic data presently available i t is i m p o s s i b l e to d i s t i n g u i s h b e t w e e n these a l t e r n a t i v e r e a c t i o n m e c h anisms. T h e w o r k d e s c r i b e d h e r e o n the C u ( I I ) - a n d a u t o x i d a t i o n of ascorbic

a c i d has b e e n

extended

Fe(III)-catalyzed

to c a t a l y t i c systems

i n v o l v i n g v a n a d y l ( 1 2 ) a n d u r a n y l ( 1 3 ) ions. O n the basis of the results d e s c r i b e d a b o v e i t w o u l d seem that there are p o t e n t i a l l y m a n y other m e t a l ions t h a t are c a p a b l e

of

undergoing redox

reactions w i t h

the

ascorbate i o n , a n d that m a y f u n c t i o n as catalysts i n the a u t o x i d a t i o n of a s c o r b i c a c i d . A n a l o g o u s m e c h a n i s m s m a y also a p p l y to systems i n v o l v i n g m e t a l - i o n catalysis of ascorbate o x i d a t i o n i n w h i c h the p r i m a r y o x i d a n t is a reagent other t h a n m o l e c u l a r o x y g e n . Metal-Chelate-Catalyzed Autoxidation of Ascorbic A c i d .

Kinetic

d a t a for r e a c t i o n systems i n w h i c h m e t a l chelates r a t h e r t h a n m e t a l ions serve as catalysts for the a u t o x i d a t i o n of ascorbic a c i d are i l l u s t r a t e d i n F i g u r e s 4, 5, a n d 6 ( 9 ) . oxygen

T h e rate constants are i n d e p e n d e n t of m o l e c u l a r

concentration a n d are m u c h lower

t h a n those

observed

for

a u t o x i d a t i o n of ascorbic a c i d i n the presence of free ( a q u o ) m e t a l ions. T h e m e t a l - c h e l a t e - c a t a l y z e d reactions are therefore e x p e c t e d to p r o c e e d t h r o u g h single e l e c t r o n transfer steps, w i t h the

first

e l e c t r o n transfer

f o l l o w e d b y m e t a l i o n d i s s o c i a t i o n a n d r e c o m b i n a t i o n of t h e d e p r o t o n a t e d ascorbate r a d i c a l a n i o n w i t h the h i g h e r v a l e n c e f o r m of the m e t a l chelate. T h u s the r e a c t i o n m e c h a n i s m is s i m i l a r to the s t o i c h i o m e t r i c r e a c t i o n s c h e m e i l l u s t r a t e d i n S c h e m e 1 w i t h a m e t a l chelate r e p l a c i n g the free metal ion.

I n a c a t a l y t i c system i n the presence

of excess m o l e c u l a r

o x y g e n a n d o n l y a r e l a t i v e l y s m a l l a m o u n t of m e t a l chelate t h e g e n e r a t i o n of the l o w e r v a l e n c e f o r m of t h e m e t a l chelate b y o x i d a t i o n of

ascorbic

a c i d is c o u n t e r - b a l a n c e d b y r a p i d r e o x i d a t i o n of the m e t a l chelate to t h e higher valence form by molecular oxygen, resulting a cyclic catalytic



7.

MARTELL


1

2

3

165

4

5

6

MOLARITY OF CATALYST X 10* Figure 4. Variation of rate constants for the autoxidation of ascorbic acid as a function of concentration of Cu(II) chelates at 25°C and —log [H ] of 3.45: EDTA = ethylenediaminetetraacetic acid; HEDTA = hydroxyethylethylenediaminetetraacetic acid; NTA = nitrilotriacetic acid; HIMDA = hydroxyethyliminodiacetic acid; IMDA = iminodiacetic acid. +

process of t h e t y p e i l l u s t r a t e d i n S c h e m e 3. T h e p s e u d o

first-order

rate

constants p l o t t e d i n F i g u r e s 4 a n d 5 s h o w l i n e a r d e p e n d e n c e of the r a t e constants o n c o p p e r c h e l a t e a n d o n i r o n c h e l a t e c o n c e n t r a t i o n s , r e s p e c t i v e l y , t h u s i n d i c a t i n g t h e f o r m a t i o n of a m i x e d l i g a n d c o m p l e x

with

ascorbate as t h e r e a c t i v e i n t e r m e d i a t e i n w h i c h t h e s l o w r a t e - d e t e r m i n i n g e l e c t r o n transfer occurs.

T h e r e a c t i o n rates are also seen to decrease

r a p i d l y w i t h a n i n c r e a s e i n the stabilities of t h e c o p p e r a n d i r o n chelates


166

ASCORBIC ACID


HIMDA

5

10

15

20

25

30

MOLARITY OF CATALYST X 106 Figure 5. Variation of rate constants for the autoxidation of ascorbic acid as a function of concentration of Fe(HI) chelates at 25° C and —log [H*] of 2.45; DTPA = diethylenetriaminepentaacetic acid; CDTA = trans-1,2-diaminocyclohexanetetraacetic acid; other terms as in caption of Figure 4. involved.

T h i s effect m a y be i n t e r p r e t e d i n one of t w o w a y s :

(i)

that

the r e a c t i o n occurs t h r o u g h a dissociative m e c h a n i s m r e l e a s i n g a s m a l l a m o u n t of the free m e t a l i o n , w h i c h t h e n acts as a catalyst for

ascorbic

a c i d o x i d a t i o n , i n t h e m a n n e r i l l u s t r a t e d i n S c h e m e 2; or ( i i ) t h a t t h e r e d o x p o t e n t i a l of t h e c o p p e r i o n i n the m i x e d

ligand-ascorbate-carrier

l i g a n d c o m p l e x stabilizes t h e h i g h e r v a l e n t f o r m of t h e m e t a l i o n to a greater extent w h e n a m o r e h i g h l y stable m e t a l chelate is i n v o l v e d as t h e catalyst.



Figure 6. Dependence of second-order rate constants for Fe(III)-chelatecatalyzed autoxidation of ascorbic acid on hydrogen ion concentration at 25°C. Abbreviations are those given in Figures 4 and 5.



Scheme 3.

Proposed mechanism for metal-chelate-catalyzed autoxidation of ascorbic acid.


9

•

o o » S o >

oo

7.

169


MARTELL

T h e p o s s i b i l i t y that the d e c r e a s e d c a t a l y t i c a c t i v i t y w i t h increase i n m e t a l chelate s t a b i l i t y represents a d i s s o c i a t i v e m e c h a n i s m i n w h i c h t h e free m e t a l i o n is a c t u a l l y the c a t a l y s t w a s e x p l o r e d b y c o m p a r i n g the o b s e r v e d rates w i t h t h e concentrations of free m e t a l i o n i n e q u i l i b r i u m w i t h the v a r i o u s chelates i n v e s t i g a t e d . S i n c e the rate constants f o r freem e t a l - i o n catalysis are k n o w n i t w a s possible to c a l c u l a t e a n d p r e d i c t t h e observed

c a t a l y t i c rate constants, since t h e e q u i l i b r i u m constants

for

d i s s o c i a t i o n of the m e t a l chelates are also k n o w n . T h e values c a l c u l a t e d i n this m a n n e r d i d n o t c o r r e l a t e w i t h the o b s e r v e d rates, i n d i c a t i n g t h a t Downloaded by UNIV OF GUELPH LIBRARY on June 5, 2012 | http://pubs.acs.org Publication Date: June 1, 1982 | doi: 10.1021/ba-1982-0200.ch007

the o b s e r v e d catalysis p r o b a b l y p r o c e e d s b y e l e c t r o n transfer f r o m t h e r e d u c t a n t to the m e t a l i o n i n the m i x e d l i g a n d chelates i l l u s t r a t e d i n S c h e m e 3.

of the

type

I n s u c h a m e c h a n i s m t h e m e t a l chelates

v i s u a l i z e d as r e m a i n i n g i n t a c t i n b o t h t h e o x i d i z e d a n d r e d u c e d t h r o u g h the

entire c a t a l y t i c c y c l e .

T h u s the d e p r o t o n a t e d

are

forms

ascorbate

r a d i c a l a n i o n a n d the c a r r i e r - l i g a n d are v i s u a l i z e d i n f o r m u l a

15

as

r e m a i n i n g s i m u l t a n e o u s l y b o u n d to the r e d u c e d m e t a l i o n a n d r e m a i n c o m b i n e d w i t h t h e m e t a l i o n w h e n it is r e o x i d i z e d to the h i g h e r v a l e n c e state [i.e., f r o m C u ( I )

to C u ( I I ) ] .

A f t e r t h e second e l e c t r o n transfer,

h o w e v e r , as i n d i c a t e d i n 16, the d e h y d r o a s c o r b i c a c i d finally f o r m e d is s u c h a w e a k l i g a n d that i t r e a d i l y dissociates

a n d the s i m p l e m e t a l

chelate i n w h i c h the m e t a l i o n is a g a i n i n its l o w e r v a l e n c e state a n d is r e o x i d i z e d b y m o l e c u l a r o x y g e n to regenerate the catalyst 13. I n the first m i x e d l i g a n d c o m p l e x f o r m e d i n the r e a c t i o n m i x t u r e , 14, the c o o r d i n a t e d ascorbate i o n is i n d i c a t e d i n its m o n o p r o t o n a t e d

form.

E x p e r i m e n t a l e v i d e n c e for the d e g r e e of p r o t o n a t i o n of this species w a s o b t a i n e d f r o m the v a r i a t i o n of the c a l c u l a t e d second-order rate constants w i t h h y d r o g e n i o n c o n c e n t r a t i o n i n the l o w p H r a n g e i n w h i c h these reactions w e r e c a r r i e d out.

T h e substrate w a s p r i m a r i l y i n its n e u t r a l

d i p r o t o n a t e d f o r m a n d the e q u i l i b r i u m i n v o l v i n g m i x e d l i g a n d c o m p l e x f o r m a t i o n results i n d i s p l a c e m e n t of one of the t w o protons present o n the e n e - d i o l groups.

T h u s the c o n c e n t r a t i o n of i n t e r m e d i a t e 14

increase as the h y d r o g e n clearly observed

ion concentration

decreases.

i n the plots of the second-order

f u n c t i o n of p H i n F i g u r e 6. and copper-chelate-catalyzed

will

T h i s effect is

rate constants

as a

S i m i l a r effects w e r e o b t a i n e d for b o t h i r o n o x i d a t i o n reactions.

a m e t a l i o n i n a m e t a l chelate c o m p o u n d

S i n c e the t e n d e n c y of

to exist i n its h i g h e r v a l e n c e

state increases w i t h the s t a b i l i t y of the m e t a l chelate c o m p o u n d , a n d i n fact its redox p o t e n t i a l c a n be c a l c u l a t e d f r o m the s t a b i l i t y constant of the m e t a l chelate itself, it w o u l d be expected t h a t i n c r e a s i n g the s t a b i l i t y of the m e t a l c h e l a t e w o u l d decrease its c a t a l y t i c a c t i v i t y for the a u t o x i d a t i o n of ascorbic a c i d , as is seen i n F i g u r e s 4 a n d 5. W h i l e i t is clear t h a t this t r e n d exists, there is n o l i n e a r c o r r e l a t i o n b e t w e e n chelate s t a b i l i t y a n d c a t a l y t i c a c t i v i t y because, i f s u c h a c o r r e l a t i o n existed, it w o u l d n o t


170

ASCORBIC

ACID

h a v e b e e n possible to e l i m i n a t e the dissociative m e c h a n i s m i n v o l v i n g a n alternate c a t a l y t i c route i n v o l v i n g the free a q u o m e t a l i o n i n its h i g h e r valence

state.

It is o b v i o u s

that t h e m o r e stable m e t a l chelates

will

h a v e a l a r g e r n u m b e r of d o n o r groups c o o r d i n a t e d to the m e t a l i o n a n d w i l l h a v e c o o r d i n a t e b o n d s that are m o r e difficult to b r e a k , a process t h a t w o u l d be necessary for the complexes w i t h m u l t i d e n t a t e l i g a n d s i n w h i c h the m e t a l i o n is n e a r l y or f u l l y c o o r d i n a t e d .

T h i s t y p e of

displacement

is i n d i c a t e d s c h e m a t i c a l l y b y f o r m u l a s 13 a n d 13a i n S c h e m e 3 i n w h i c h the m e t a l ions [ C u ( I I ) ] are r e p r e s e n t e d as b e i n g t e t r a - c o o r d i n a t e d . Downloaded by UNIV OF GUELPH LIBRARY on June 5, 2012 | http://pubs.acs.org Publication Date: June 1, 1982 | doi: 10.1021/ba-1982-0200.ch007

formation

of

a mixed

ligand complex

r e q u i r e d for

an

The

inner-sphere

electron transfer of the t y p e i n d i c a t e d i n f o r m u l a s 14, 15, a n d 16 w o u l d i n v o l v e d i s p l a c e m e n t of one or m o r e of the c o o r d i n a t e d d o n o r

groups

of the c a r r i e r l i g a n d . It is e x p e c t e d t h a t c o n s i d e r a b l e steric effects w o u l d be associated w i t h s u c h d i s p l a c e m e n t processes a n d t h a t these

effects

w o u l d v a r y i n a v e r y c o m p l e x w a y w i t h the nature of the l i g a n d i n the c a t a l y t i c m e t a l chelate. F i n a l l y it s h o u l d be p o i n t e d out that t h e r e is a n alternate m e c h a n i s m for

the

two

successive

electron

transfer processes i n d i c a t e d

by

the

sequence 14—» 15 - » 16 - » 13 a. I t is q u i t e p o s s i b l e t h a t the ascorbate r a d i c a l a n i o n dissociates f r o m the m i x e d l i g a n d c o m p l e x r e o x i d a t i o n of

the C u ( I )

ion, and recombines

15, p r i o r to

w i t h another

Cu(II)

chelate p r i o r to the final e l e c t r o n transfer step i n d i c a t e d b y 16 —> 17

+

10. T h i s represents a slight m o d i f i c a t i o n of the m e c h a n i s m s i n S c h e m e 3, a n d i n v o l v e s a n alternate b r a n c h for r e a c t i o n sequence 15 - » 1 6 - * T h e m a i n difference b e t w e e n the F e ( I I I ) a n d C u ( I I )

17.

ion-catalyzed

a u t o x i d a t i o n of ascorbic a c i d o n one h a n d , a n d the F e ( I I I )

and C u ( I I )

c h e l a t e - c a t a l y z e d o x i d a t i o n reactions is the l a c k of d e p e n d e n c e of

the

latter systems o n the c o n c e n t r a t i o n of m o l e c u l a r o x y g e n , a n d t h e absence of a t e r n a r y m e t a l s u b s t r a t e - c a r r i e r l i g a n d - d i o x y g e n c o m p l e x as a n i n t e r m e d i a t e i n the p r o p o s e d

reaction mechanism.

T h e absence of s u c h a n

i n t e r m e d i a t e m a y b e c o n s i d e r e d to be d u e at least i n p a r t to the o c c u p a t i o n of a l l or n e a r l y a l l the c o o r d i n a t i o n positions of t h e m e t a l i o n b y the c a r r i e r l i g a n d , thus c r o w d i n g relatively weak monodentate

out the d i o x y g e n ,

w h i c h is at best a

l i g a n d . It s h o u l d also be n o t e d that the

p r o p o s e d m e c h a n i s m i n S c h e m e 3 i n v o l v e s t w o successive electron t r a n s fers r a t h e r t h a n a single i o n i c t y p e t w o - e l e c t r o n shift of the t y p e i n d i c a t e d i n S c h e m e 2. over

It is not i n t e n d e d at this stage to f a v o r one

the other; b o t h s h o u l d be

considered

alternatives.

mechanism A

factor

in

ascorbate a u t o x i d a t i o n t h a t m a y not a p p l y to m a n y other substrates is the resonance

s t a b i l i z a t i o n of t h e one-electron

the ascorbate r a d i c a l a n i o n . oxidation products

are s t a b i l i z e d b y resonance

factors, the one-electron

oxidation intermediate,

I n cases w h e r e one-electron

transfer process m a y

r e d u c t i o n of

or other c o n s t i t u t i o n a l be

favored

over

e l e c t r o n r e d o x reactions.


two-

7.

171


MARTELL

Ascorbic Acid Oxidase A s c o r b i c a c i d oxidase is a c t i v a t e d b y C u ( I I ) i o n a n d is b e l i e v e d to f u n c t i o n i n a m a n n e r s i m i l a r to the m e c h a n i s m i n d i c a t e d i n S c h e m e

3

i n v o l v i n g a series of t w o successive one-electron transfer steps i n w h i c h the a s c o r b i c

a c i d is o x i d i z e d to

a n i n t e r m e d i a t e free

radical anion

c o o r d i n a t e d at the active site i n a m a n n e r s i m i l a r to t h a t i n d i c a t e d b y f o r m u l a 15. I n the e n z y m i c system i t seems l i k e l y that t h e i n t e r m e d i a t e ascorbate free r a d i c a l w o u l d r e m a i n c o o r d i n a t e d to the m e t a l i o n i n b o t h


Cu(I) and

and C u ( I I )

reassociation

forms, r a t h e r t h a n u n d e r g o steps

that w o u l d

t e n d to

successive

greatly

dissociation

slow

down

the

e n z y m i c r e a c t i o n process. I n this respect the e n z y m i c m e c h a n i s m

may

differ f r o m that suggested i n S c h e m e 3 for m e t a l chelate catalysis of t h e a u t o x i d a t i o n of ascorbic a c i d , since there is no e v i d e n c e i n t h e latter case t h a t the w e a k C u ( I )

intermediate complex

w o u l d h o l d together

e n o u g h f o r the r e o x i d a t i o n step to o c c u r (see

discussion later).

long Since

the m e t a l i o n w o u l d r e m a i n b o u n d to t h e active site of the e n z y m e , its reoxidation by

molecular

oxygen

may

very

w e l l occur

through

the

f o r m a t i o n of a d i o x y g e n c o m p l e x , thus p r o v i d i n g a n a d d i t i o n a l r e a c t i o n i n t e r m e d i a t e . A s m e n t i o n e d before, the free r a d i c a l ascorbate a n i o n is r e s o n a n c e - s t a b i l i z e d a n d its f o r m a t i o n i n these systems i n a p p r e c i a b l e q u a n t i t i e s therefore seems reasonable.

A n o t h e r p r o b a b l e difference

be

t w e e n the e n z y m i c m e c h a n i s m a n d the m e c h a n i s m suggested i n S c h e m e 3 for m e t a l chelate catalysis is the d i s p l a c e m e n t of some of the l i g a n d d o n o r groups f r o m the c o o r d i n a t i o n sphere of the m e t a l i o n that w o u l d b e r e q u i r e d for the f o r m a t i o n of t h e m i x e d l i g a n d complexes i n w h i c h the e l e c t r o n transfer process takes p l a c e .

Such displacement

reactions

w o u l d greatly s l o w d o w n a n d i n h i b i t the r e a c t i o n rate a n d i t is b e l i e v e d t h a t the e n z y m e c e r t a i n l y w o u l d e l i m i n a t e s u c h r e a c t i o n b a r r i e r s b y the d e s i g n of a c o o r d i n a t i o n sphere t h a t w o u l d m a k e a v a i l a b l e at least t w o l a b i l e c o o r d i n a t i o n sites of C u ( I I ) for c o m b i n a t i o n w i t h the substrate.

Rate Laws for Metal-Ion- and Metal-Chelate-Catalyzed Autoxidation of Ascorbic Acid O n the basis of k i n e t i c d a t a of the t y p e i l l u s t r a t e d i n F i g u r e s 1, 2, a n d 3 the rate l a w of a u t o x i d a t i o n of a s c o r b i c a c i d is represented

by

E q u a t i o n 1, i n v o l v i n g a t h i r d - o r d e r rate constant a n d a r e a c t i o n rate that is first o r d e r oxygen.

i n substrate m o n o a n i o n ,

metal ion, and

molecular

Since the r a t e - d e t e r m i n i n g step i n v o l v e s e l e c t r o n transfer i n a

ternary complex, third-order behavior involves two pre-equilibria, E q u a tions 2 a n d 3, for the f o r m a t i o n of the t e r n a r y c o m p l e x , a n d a f i n a l s l o w step, E q u a t i o n 4, i n w h i c h t h e c o o r d i n a t e d e l e c t r o n r e d u c t i o n to h y d r o g e n p e r o x i d e .

o x y g e n undergoes

a two-

A s pointed out b y T a q u i K h a n

a n d M a r t e l l ( 9 ) , the h y d r o g e n p e r o x i d e r a p i d l y d i s a p p e a r s a n d is n o t


172

ASCORBIC

detected

i n t h e final r e a c t i o n m i x t u r e . T h e h y d r o g e n p e r o x i d e

ACID

formed

m a y be r e c o n v e r t e d to o x y g e n a n d w a t e r t h r o u g h t h e c a t a l a s e - l i k e a c t i o n of the c u p r i c i o n or of some of its complexes.

" Cu

fc

+

2 +

CuHA


[ ~n m]

=

H A " ^± C u H A +

+

HL

0

^

2

(i)

Cu2

(2)

+

CuHA0

2

(3)

+

slow

CuHACV + The

H

metal-chelate-catalyzed

dependent

> Cu

+

+ A +

2 +

H 0 2

a u t o x i d a t i o n of

(4)

2

ascorbic

o n the c o n c e n t r a t i o n of m o l e c u l a r o x y g e n .

a c i d is

not

O n the basis of

the d a t a i l l u s t r a t e d i n F i g u r e s 4, 5, a n d 6 the rate expression

suggested

for this t y p e of r e a c t i o n is g i v e n b y E q u a t i o n 5, w h i c h i n d i c a t e s that t h e d i s a p p e a r a n c e of the m o n o a n i o n of t h e substrate is first o r d e r i n b o t h m e t a l chelate a n d the ascorbate m o n o a n i o n .

T h u s the r e a c t i o n sequences

i n d i c a t e d b y E q u a t i o n s 6, 7, a n d 8 consist of a p r e - e q u i l i b r i u m i n v o l v i n g t h e f o r m a t i o n of a m i x e d l i g a n d m e t a l - c a r r i e r l i g a n d - s u b s t r a t e m o n o anion complex.

F o l l o w i n g the r a t e - d e t e r m i n i n g e l e c t r o n transfer r e a c t i o n

w i t h i n the m i x e d l i g a n d c o m p l e x of the m e t a l c o m p l e x

( E q u a t i o n 7 ) , the l o w e r v a l e n c e

is r a p i d l y r e o x i d i z e d i n s o l u t i o n b y

o x y g e n , thus r e g e n e r a t i n g t h e catalyst.

form

molecular

H A represents a m u l t i d e n t a t e n

l i g a n d , a n d H L is a s c o r b i c a c i d . 2

-

C u

d

[

ii (2-n A

^ " L

) +

=

]

+

fc[HL"]

[CuA " ( 2

n ) +

]

(5)

HL"— Cu (A) (HL) " n

a

(6)

n ) +

slow

Cu (A) (HL) -» n

( 1

) +

>CuW ""'* +

L" +

1

H

(7)

+

fast

Free radicals

>A + CuA< - > , 2

n

+

0

H 0 2

R e c e n t l y J a m e s o n a n d B l a c k b u r n (14,15,16) alternate m e c h a n i s m for the c o p p e r - c a t a l y z e d

have

complex

an

ascorbic (17)

of

a n i o n , a n d the s u b s e q u e n t f o r m a t i o n of a n i n t e r m e d i a t e

peroxo type C u ( I I ) - d i o x y g e n - a s c o r b a t e d a t a suggested

suggested

a u t o x i d a t i o n of

a c i d , i n v o l v i n g the f o r m a t i o n of a b i n u c l e a r C u ( I I ) t h e ascorbate

(8)

2

2

complex

(18).

Their kinetic

a v a r i e t y of rate b e h a v i o r d e p e n d i n g o n t h e n a t u r e of

the s u p p o r t i n g electrolyte.

F o r m u l a 17, w h i c h w a s p o s t u l a t e d for n i t r a t e


7.

MARTELL

0


173


H

CHOHCH OH 2

I n i t i a l b i n u c l e a r complex, ( C u H L )

2

2 +

, 17

I n t e r m e d i a t e d i o x y g e n c o m p l e x , C u H L 0 C u H L , 18 2

m e d i a , seems to suggest the rate i n d i c a t e d b y E q u a t i o n 9.

Thus

the

r e a c t i o n sequence suggested consists of t w o p r e - e q u i l i b r i a , E q u a t i o n s 10 a n d 11, w h i c h r e s u l t i n the f o r m a t i o n d i o x y g e n c o m p l e x , 18. transfer

(Equation

of

the dinuclear peroxo

T h i s is f o l l o w e d b y a r a t e - d e t e r m i n i n g

12),

w h i c h results i n the f o r m a t i o n

of

type

electron two

free

r a d i c a l s that are c o n v e r t e d to final p r o d u c t s i n s u b s e q u e n t steps t h a t seem to be p a r t i a l l y rate d e t e r m i n i n g . I n c h l o r i d e m e d i a [ a n d p r o b a b l y i n the

^

2

=

J

fc'[Cu ][HL-][0 ] 2+

2CuHL — +

(CuHL)

2

+

2 +

0

(CuHL)

2

(10)

2 +

2

^± C u H L 0 C u H L

2

(9)

1/2

2

(11)

2 +

slow

CuHL0 CuHL 2

2 +

>LCu0 H- + 2

Cu

2 +

+

L-

(12)

free r a d i c a l s - » products

(13)

p r e s e n c e of other anions that c o o r d i n a t e C u ( I I ) ] t h e c h l o r i d e i o n seems to p a r t i c i p a t e i n b i n u c l e a r c o m p l e x f o r m a t i o n , a n d f u r t h e r

complicates

the kinetics.


174

ASCORBIC A C I D

T h e h a l f - o r d e r d e p e n d e n c e of t h e rate of a u t o x i d a t i o n of

ascorbic

a c i d o n m o l e c u l a r o x y g e n that w a s f o u n d b y B l a c k b u r n a n d J a m e s o n a n d that w a s the basis for t h e i r suggestion of b i n u c l e a r i n t e r m e d i a t e s 17 a n d 18, is q u i t e i n t e r e s t i n g , e s p e c i a l l y i n v i e w of the fact t h a t p e r o x o b r i d g e d d i o x y g e n complexes analogous to 18 h a v e also b e e n o b s e r v e d for c o b a l t d i o x y g e n c o m p l e x systems (17).

A s n o t e d a b o v e , the

first-order

dioxygen

d e p e n d e n c e o b s e r v e d b y T a q u i K h a n a n d M a r t e l l ( 9 ) undergoes a t r a n s i t i o n at l o w o x y g e n concentrations to l o w e r order d e p e n d e n c e a n d

finally

z e r o - o r d e r d e p e n d e n c e as i n d i c a t e d i n F i g u r e 3. T h u s it m a y v e r y w e l l Downloaded by UNIV OF GUELPH LIBRARY on June 5, 2012 | http://pubs.acs.org Publication Date: June 1, 1982 | doi: 10.1021/ba-1982-0200.ch007

b e that at l o w o x y g e n concentrations b i n u c l e a r complexes

of the k i n d

o b s e r v e d b y B l a c k b u r n a n d J a m e s o n b e c o m e the r e a c t i o n i n t e r m e d i a t e s for a u t o x i d a t i o n of ascorbic

a c i d , r e s u l t i n g i n the o b s e r v e d

d e p e n d e n c e of the r e a c t i o n rates o n o x y g e n c o n c e n t r a t i o n . h a n d , b i n u c l e a r complexes

half-order

O n the other

of the t y p e i l l u s t r a t e d , 17 a n d 18, t e n d to

f o r m o n l y i n solutions i n w h i c h the m e t a l i o n c o n c e n t r a t i o n is at least m o d e r a t e l y h i g h . T h e r e f o r e i n solutions i n w h i c h t h e c a t a l y t i c species, either the C u ( I I ) or F e ( I I I ) ions, or t h e i r m e t a l chelates, are present at v e r y l o w concentrations the f o r m a t i o n of b i n u c l e a r c o m p l e x i n t e r m e d i a t e s is not v e r y l i k e l y .

U n d e r s u c h c o n d i t i o n s , catalysis b y

mononuclear

complexes of the types i n d i c a t e d i n Schemes 2 a n d 3 w o u l d seem to be favored. It is i n t e r e s t i n g to note that the + 3

o x i d a t i o n state of c o p p e r has

b e e n i n v o k e d b y J a m e s o n a n d B l a c k b u r n (15,16) d i o x y g e n complexes.

i n the f o r m a t i o n of

A l t h o u g h this is a n a t t r a c t i v e i d e a i n v i e w of recent

investigations r e p o r t e d b y M a r g e r u m et a l . (18),

the f o r m a t i o n of stable

C u ( I I I ) complexes i n aqueous s o l u t i o n w o u l d r e q u i r e c o o r d i n a t i o n w i t h l i g a n d s h a v i n g v e r y s p e c i a l properties.

H e r e a g a i n i t seems

somewhat

u n l i k e l y that a p p r e c i a b l e concentrations of C u ( I I I ) complexes are f o r m e d i n these r e a c t i o n systems.

O n the other h a n d , C u ( I I I ) m a y b e i n v o k e d

for e x p l a i n i n g the stabilities of C u ( I I ) - d i o x y g e n

complexes

of the t y p e

i l l u s t r a t e d i n S c h e m e 2, a n d 18. T h u s t h e d i o x y g e n c o m p l e x i n t e r m e d i a t e s f o r m e d i n trace a m o u n t s i n these r e a c t i o n systems m a y b e

considered

to i n v o l v e o x i d a t i o n of c o p p e r to a n i n t e r m e d i a t e o x i d a t i o n state b e t w e e n C u ( I I ) and C u ( I I I ) .

Role of Ascorbic Acid in a Mono-oxygenase Model (U den friend's System) R e c e n t l y ascorbic a c i d has b e e n assigned a significant f u n c t i o n i n the reactions i n v o l v i n g o x y g e n i n s e r t i o n b y m o d e l oxygenase a n d peroxidase systems i n w h i c h f e r r i c i o n or a f e r r i c chelate is c o n s i d e r e d to b e t h e catalyst.

A l t h o u g h reaction mechanisms

involved ascorbic

acid merely

suggested

b y earlier workers

as a r e d u c t a n t to c o n v e r t

Fe(III)

to

F e ( I I ) , w h i c h w o u l d t h e n i n t u r n i n t e r a c t w i t h the o x i d a n t , H a m i l t o n


7.

175


MARTELL

suggested that ascorbate or s i m i l a r reductants s u c h as c a t e c h o l are

(11)

i n v o l v e d i n the f o r m a t i o n of a t e r n a r y c o m p l e x i n w h i c h the m e t a l i o n is c o o r d i n a t e d s i m u l t a n e o u s l y to the r e d u c t a n t a n d the o x i d a n t . T h e r e a c t i o n sequences o r i g i n a l l y suggested for o x y g e n i n s e r t i o n i n a substrate s u c h as s a l i c y c l i c a c i d i n U d e n f r i e n d ' s S y s t e m (19-22) w h i c h molecular oxygen

is the o x i d a n t a n d a n i r o n chelate

in

s u c h as

F e ( I I ) - E D T A is the catalyst a n d ascorbic a c i d is the r e d u c t a n t , is i n d i c a t e d b y E q u a t i o n s 14-18.

I n this r e a c t i o n sequence o x y g e n i n s e r t i o n

is c o n s i d e r e d to o c c u r b y d i r e c t r e a c t i o n of the a r o m a t i c c o m p o u n d H0 Downloaded by UNIV OF GUELPH LIBRARY on June 5, 2012 | http://pubs.acs.org Publication Date: June 1, 1982 | doi: 10.1021/ba-1982-0200.ch007

2

with

a n d O H - free r a d i c a l s , a n d the ascorbate r e d u c t a n t m e r e l y serves

the p u r p o s e of r e g e n e r a t i n g the F e ( I I ) chelate as i n d i c a t e d b y E q u a t i o n s 16 a n d 17.

Fe -EDTA +

0

n

COO

+

2

H 0 -> F e - E D T A + m

2

COO"

OH" +

COO"

(+OH-)

2

Fe -EDTA + m

Fe -EDTA + m

H A + O H " -» F e - E D T A + n

2

HA- +

H A - - f O H " -> F e - E D T A + A + n

Fe -EDTA + H 0 n

(14)

2

COO"

(+H 0 ) 2

H0 -

2

2

-> F e - E D T A + m

OH- +

H 0

(16)

2

H 0

(17)

2

OH"

(18)

O n the basis of the facts t h a t o x y g e n i n s e r t i o n occurs p r e f e r e n t i a l l y at the ortho a n d para positions r e l a t i v e to the a c t i v a t i n g h y d r o x y l g r o u p o n the a r o m a t i c r i n g , a n d that t h e r e a c t i o n d i d not seem to i n v o l v e free r a d i c a l s , H a m i l t o n (11)

suggested a n i o n i c m e c h a n i s m i n v o l v i n g a t e r n a r y

ascorbate m e t a l d i o x y g e n c o m p l e x of the t y p e i l l u s t r a t e d b y 19 i n S c h e m e 4. I n t h e p r o p o s e d m e c h a n i s m a c o n c e r t e d shift of e l e c t r o n p a i r s results i n t h e i n s e r t i o n of a n o x y g e n a t o m i n t o the substrate a n d a c o n c o m i t a n t t w o - e l e c t r o n r e d u c t i o n of ascorbate to d e h y d r o a s c o r b i c a c i d . A n alternate e l e c t r o n transfer sequence is, of course, possible i n v o l v i n g t w o

single

e l e c t r o n transfer steps a n d the f o r m a t i o n of a n i n t e r m e d i a t e c o m p l e x i n w h i c h the ascorbate a n i o n r a d i c a l is c o o r d i n a t e d to t h e m e t a l i o n .

The

m e c h a n i s m p r o p o s e d i n S c h e m e 4 is s o m e w h a t m o r e s a t i s f y i n g t h a n t h e p r e v i o u s l y r e c o m m e n d e d free r a d i c a l m e c h a n i s m ( E q u a t i o n 1 4 - 1 8 )


be-


176

ASCORBIC

| CH OH

CH.OH Scheme 4.

ACID

20

2

Proposed mechanism for Fe(II)-catalyzed oxygen insertion (UdenfrieruTs system).

cause i t assigns a m o r e i m p o r t a n t r o l e to t h e m e t a l i o n that is a n essential catalyst i n these e n z y m e m o d e l systems. A similar mechanism illustrated i n Scheme b y H a m i l t o n ( I I ) for peroxidase

model

5 has b e e n

systems

suggested

(22) i n w h i c h the

o x i d a n t is h y d r o g e n p e r o x i d e , t h e r e d u c t a n t is a s c o r b i c a c i d o r a n a n a l o gous reagent s u c h as c a t e c h o l , a n d t h e c a t a l y t i c m e t a l i o n is F e ( I I I ) . I n this system t h e i n t e r m e d i a t e t e r n a r y c o m p l e x undergoes a n i n t r a m o l e c u l a r e l e c t r o n transfer i n v o l v i n g fission of t h e o x y g e n - o x y g e n

b o n d of t h e

p e r o x i d e l i g a n d to g i v e w a t e r a n d a n i n t e r m e d i a t e c o m p l e x t h a t essentially i n v o l v e s c o o r d i n a t i o n of a t o m i c o x y g e n w i t h F e ( I I I ) .

This intermediate

is s o m e w h a t s t a b i l i z e d b y several resonance f o r m s (21a-c) i n w h i c h some n e g a t i v e c h a r g e is seen to reside o n t h e o x y g e n a t o m , thus a c c o u n t i n g f o r its a b i l i t y to r e m a i n briefly c o o r d i n a t e d w i t h t h e m e t a l i o n . I n s e r t i o n of a t o m i c o x y g e n i n t o a n a p p r o p r i a t e substrate results i n r e g e n e r a t i o n of



7.

177


MARTELL

Scheme 5.

Proposed mechanism for a model peroxidase system.

t h e F e ( I I I ) c o m p l e x 6 of the r e d u c i n g l i g a n d .

R e d u c t i o n of

Fe(III)

b y the ascorbate l i g a n d is p r e v e n t e d b y t h e o x i d a n t , h y d r o g e n p e r o x i d e , to regenerate

the o r i g i n a l r e a c t i v e t e r n a r y c o m p l e x ,

21.

Hamilton's

m e c h a n i s m for these p e r o x i d a s e m o d e l reactions is of interest because of its s i m i l a r i t y

to

the

reactions

o c c u r r i n g i n catalase

and

peroxidase

e n z y m i c systems i n w h i c h resonance forms of the i r o n p o r p h y r i n r i n g system s t a b i l i z e a t w o - e l e c t r o n o x i d a n t i n t e r m e d i a t e b e l i e v e d to i n v o l v e a coordinated oxygen atom.


178

ASCORBIC ACID


Literature Cited 1. Smith, R. M.; Martell, A. A. "Critical Stability Constants"; Plenum: New York, 1977. 2. Hvoslef, J. Acta Crystallogr., Sect. B 1974, 30, 2711. 3. Hughes, D. L. J. Chem. Soc., Dalton Trans. 1973, 2209. 4. Hvoslef, J. Acta Crystallogr., Sect. B 1969, 25, 2214. 5. Kriss, E. E. Russ. J. Inorg. Chem. 1978, 23(7), 1004. 6. Evtushenko, N. P.; Yatsimirskii, K. B.; Kriss, E. E.; Kurbatova, G. T. Zh. Neorg. Kim. 1977, 22, 1543. 7. Kriss, E. E.; Kurbatova, G. T.; Kuts, V. S.; Prokopenko, V. P. Zh. Neorg. Khim. 1976, 21, 2978. 8. Taqui Khan, M. M.; Martell, A. E. J. Am. Chem. Soc. 1967, 89, 4176. 9. Ibid., 7104. 10. Dekker, A. O.; Dickinson, R. G. J. Am. Chem. Soc. 1940, 62, 2165. 11. Hamilton, G. A. Adv. Enzymol. Delat. Subj. Biochem. 1969, 32, 55. 12. Taqui Khan, M. M.; Martell, A. E. J. Am. Chem. Soc. 1968, 90, 6011. 13. Ibid., 1969, 91, 4468. 14. Jameson, R. F.; Blackburn, N. J. J. Inorg. Nucl. Chem. 1975, 37, 809. 15. Jameson, R. F.; Blackburn, N. J. J. Chem. Soc., Dalton Trans. 1976, 534. 16. Ibid., 1596. 17. McLendon, G.; Martell, A. E. Coord. Chem. Rev. 1976, 19, 1. 18. Margerum, D. W.; Chellappa, K. L.; Bossu, F. P.; Burce, G. S. J. Am. Chem. Soc. 1975, 97, 6894. 19. Udenfried, S.; Clark, C. T.; Axelrod, J.; Brodie, B. B. J. Biol. Chem. 1954, 208, 731. 20. Brodie, B. B.; Axelrod, J.; Shore, P. A.; Udenfriend, S. J. Biol. Chem. 1954, 208, 741. 21. Mason, H. S.; Onoprienko, I.; Buhler, E. Biochim. Biophys. Acta 1957, 24, 225. 22. Taqui Khan, M. M.; Martell, A. E. "Homogeneous Catalysis by Metal Complexes: Activation of Small Inorganic Molecules"; Academic: New York, 1974; Vol. 1, p. 151. RECEIVED for review January 22, 1981. ACCEPTED May 11, 1981.


Ascorbic Acid - American Chemical Society

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