COORDINATION OF
CALCIUM AND LANTHANIDE CATIONS BY
(HYDR)OXYCARBOXYLATES IN WATER
AS STUDIED BY
MULTINUCLEAR MAGNETIC RESONANCE
• V I «C . A . M . Vijverberg
CALCIUM AND LANTHANIDE CATIONS BY
(HYDR)OXYCARBOXYLATES IN WATER
AS STUDIED BY
MULTINUCLEAR MAGNETIC RESONANCE
n o o o N) 00 CD cr> BIBLIOTHEEK TU Delft P 1776 5128 C 861072
- • ... X -r >/
COORDINATION OF
CALCIUM AND LANTHANIDE CATIONS BY
(HYDR)OXYCARBOXYLATES IN WATER
AS STUDIED BY
MULTINUCLEAR MAGNETIC RESONANCE
Proefschrift ter verkrijging van
de graad van doctor in de
technische wetenschappen
aan de Technische Hogeschool Delft,
op gezag van de Rector Magnificus,
Prof.lr. B.P.Th. Veltman,
in het openbaar te verdedigen
ten overstaan van het College van Dekanen
op dinsdag 22 mei 1984
te 16.00 uur door
Cornelis Adrianus Maria Vijverberg,
geboren te Naaldwijk,
scheikundig ingenieur
Dit proefschrift is goedgekeurd door de promotor
prof.dr.ir. H. van Bekkum
Dit proefschrift kwam tot stand onder de dagelijkse leiding van
dr.ir. A.P.G. Kieboom en dr.ir. J.A. Peters.
The investigation described in this thesis has been supported by the
Netherlands Foundation for Chemical Research (SON) with financial aid from
the Netherlands Organization for the Advancement of Pure Research (ZWO).
Typing : Mrs. M.A.A. van der Kooij-van Leeuwen
Drawings: W.J. Jongeleen
C o n t e n t s
I I n t r o d u c t i o n 1
I I A s t u d y o f d y s p r o s i u m ( I I I ) h y d r o x y - and e t h e r c a r b o x y l a t e 4 complexes i n aqueous medium u s i n g l a n t h a n i d e i n d u c e d
oxygen-17 NMR s h i f t s A b s t r a c t A I n t r o d u c t i o n A A p p r o a c h t o d a t a a n a l y s i s 5 O r i g i n of i n d u c e d s h i f t s 5 F a s t l i g a n d exchange 6 Slow l i g a n d exchange 7 Water exchange 8 Complex s t o i c h i o m e t r y 8 R e s u l t s and d i s c u s s i o n 8 ^ 0 c h e m i c a l s h i f t s 8 F a s t l i g a n d exchange 11 I n t e r p r e t a t i o n o f 1 70 D y l S o f i n d i v i d u a l compounds 1A Slow l i g a n d exchange 17 C o n c l u s i o n s 19 E x p e r i m e n t a l 19 R e f e r e n c e s 20 I I I S y n t h e s i s of ^ C ~ e n r i c h e d sodium s a l t s o f h y d r o x y - and 23 e t h e r c a r b o x y l a t e s A b s t r a c t 23 I n t r o d u c t i o n 23 S y n t h e s i s o f ^ 0 - e n r i c h e d compounds 25 E x p e r i m e n t a l 29 R e f e r e n c e s 3A
IV The use of lanthanum-139 NMR i n the s t u d y of t h e 35 c o m p l e x a t i o n b e h a v i o u r of ( h y d r o x y ) c a r b o x y l a t e a n i o n s
A b s t r a c t 35 I n t r o d u c t i o n 35 R e s u l t s and d i s c u s s i o n 37
V I I I L i n e w i d t h s 44 Slow exchange 47 C o n c l u s i o n s 47 E x p e r i m e n t a l 47 R e f e r e n c e s 48 V An NMR s t u d y o f g a d o l i n i u m ( I I I ) ( h y d r ) o x y c a r b o x y l a t e 49 complexes i n aqueous medium u s i n g G d ( I I I ) i n d u c e d ^3C
r e l a x a t i o n r a t e enhancements A b s t r a c t 49 I n t r o d u c t i o n 50 T h e o r y 50 R e s u l t s and d i s c u s s i o n 52 C o n c l u s i o n s 63 E x p e r i m e n t a l 63 R e f e r e n c e s 63 V I The c o m p l e x a t i o n o f c a l c i u m ( I I ) and l a n t h a n i d e ( I I I ) 65 c a t i o n s w i t h t h e phosphate s u b s t i t u t e ( c a r b o x y m e t h o x y ) -s u c c i n a t e (CMOS) a -s -s t u d i e d by m u l t i n u c l e a r m a g n e t i c r e s o n a n c e s p e c t r o s c o p y A b s t r a c t 65 I n t r o d u c t i o n 65 R e s u l t s o f ( c a r b o x y m e t h o x y ) s u c c i n a t e (CMOS) 67 1H NMR s p e c t r u m o f r a c e m i c CMOS 67 *H c a t i o n i n d u c e d s h i f t s o f r a c e m i c CMOS 68 Comparison o f t h e *H L n ( I I I ) i n d u c e d s h i f t s 70 H E u ( I I I ) i n d u c e d s h i f t s o f n o n - r a c e m i c CMOS 74 pH dependence o f t h e L I S o f r a c e m i c CMOS 77 C NMR spectrum o f r a c e m i c CMOS 78 1 3C P r ( I I I ) i n d u c e d s h i f t s o f r a c e m i c CMOS 79 13 C T j r e l a x a t i o n r a t e enhancements o f r a c e m i c CMOS 79 1 70 NMR 80 R e s u l t s o f o x y d i a c e t a t e (ODA) 80 lH P r ( I I I ) i n d u c e d s h i f t s 80 ^3C l o n g i t u d i n a l r e l a x a t i o n r a t e enhancements 81 pH dependence 81 1 3 9L a NMR 82
H l o n g i t u d i n a l r e l a x a t i o n r a t e enhancements 82 1 70 NMR 83 D i s c u s s i o n 83 C o n c l u s i o n s 87 E x p e r i m e n t a l 88 R e f e r e n c e s 91 V I I X-ray a n a l y s i s of ( E ) - 2 - ( c a r b o x y m e t h o x y ) ( 3 - ^ H ) m a l e i c 94 a c i d d i h y d r a t e , C6H5 2H07.2H20 P r e l i m i n a r y i n f o r m a t i o n 94 C r y s t a l d a t a 94 I n t e n s i t y d a t a , s t r u c t u r e d e t e r m i n a t i o n and r e f i n e m e n t 95 Comments 97 Acknowledgements 98 R e f e r e n c e s 98 V I I I C h i r a l i n t e r a c t i o n s between e u r o p i u m ( I I I ) - ( S )- 99 ( c a r b o x y m e t h o x y ) s u c c i n a t e (Eu(_S)-CMOS) and some sodium
p o l y c a r b o x y l a t e s as s t u d i e d by *H NMR s p e c t r o s c o p y A b s t r a c t 99 I n t r o d u c t i o n 99 R e s u l t s and d i s c u s s i o n 100 S y n t h e s i s o f Eu(_S)-CM0S 100 R e s o l u t i o n o f e n a n t i o m e r i c m o l e c u l e s 100 R e s o l u t i o n of m o l e c u l e s c o n t a i n i n g e n a n t i o t o p i c 102 n u c l e i S e l f - r e s o l u t i o n of e n a n t i o m e r i c m i x t u r e s o f Na3CM0S 104 C o n c l u s i o n s 107 E x p e r i m e n t a l 108 R e f e r e n c e s 109 IX C o n c l u d i n g remarks 110 X Summary 113 X I S a m e n v a t t i n g 116
I
INTRODUCTION
C o o r d i n a t i o n phenomena o f c a t i o n s by p o l y o x y g e n s compounds o f t e n p l a y an i m p o r t a n t r o l e i n b o t h b i o l o g i c a l and c h e m i c a l s y s t e m s . I n p a r t i c u l a r , t h e c o o r d i n a t i o n o f c a l c i u m ( I I ) by o r g a n i c compounds i s of i n t e r e s t because o f i t s r e g u l a t i n g a c t i o n i n many b i o l o g i c a l processes'' and because of i t s
t e c h n o l o g i c a l i m p o r t a n c e . As an example, t h e w o r l d w i d e s e a r c h f o r an o r g a n i c 2 3 s u b s t i t u t e o f p e n t a sodium t r i p o l y p h o s p h a t e i n d e t e r g e n t s may be m e n t i o n e d * . These e x t e n s i v e i n d u s t r i a l r e s e a r c h programs p r o v i d e d a l a r g e number of new c a l c i u m ( I I ) c o m p l e x i n g a g e n t s . Because o f e n v i r o n m e n t a l r e a s o n s t h e s e new compounds b e l o n g p r e d o m i n a n t l y t o t h e c l a s s o f sodium p o l y c a r b o x y l a t e s , t h u s c o n t a i n i n g a p a r t from t h e c a t i o n o n l y c a r b o n , h y d r o g e n and oxygen. I n g e n e r a l , the s t a b i l i t y c o n s t a n t s of the complexes w i t h c a l c i u m ( I I ) , t h e e f f e c t i v e n e s s i n d e t e r g e n t f o r m u l a t i o n s and t h e b i o d e g r a d a b i l i t y of t h e new compounds have been d e t e r m i n e d , but no d a t a on t h e s t r u c t u r e of the c a l c i u m ( I I ) complexes i n w a t e r were g i v e n . I n o r d e r t o deepen t h e i n s i g h t i n t o t h e p r e c i s e c o o r d i n a t i o n phenomena t h e d e t e r m i n a t i o n of the s t r u c t u r e of t h e c a l c i u m ( I I ) complexes of t h e s e p o l y o x y g e n compounds i n w a t e r i s i n d i s p e n s a b l e . The aim o f t h e
i n v e s t i g a t i o n s d e s c r i b e d i n t h i s t h e s i s was t h e development of methods f o r t h e s t r u c t u r e d e t e r m i n a t i o n o f t h i s type of c a l c i u m ( I I ) complexes i n w a t e r . A p a r t f r o m t h e k i n e t i c s and thermodynamics o f c o o r d i n a t i o n p r o c e s s e s , knowledge of the donor s i t e s and t h e c o n f o r m a t i o n o f t h e p o l y o x y g e n l i g a n d s i s o f g r e a t i m p o r t a n c e . The knowledge o b t a i n e d may be o f g r e a t v a l u e f o r t h e f u r t h e r development o f c a l c i u m c o m p l e x i n g compounds.
I n t h e s t u d y o f t h e donor s i t e s and t h e c o n f o r m a t i o n of o r g a n i c compounds i n s o l u t i o n t h e use of n u c l e a r m a g n e t i c r e s o n a n c e (NMR) seems t o be an o b v i o u s c h o i c e . F i r s t , the p r e s e n t g e n e r a t i o n o f h i g h f i e l d s p e c t r o m e t e r s has opened new p o s s i b i l i t i e s and s e c o n d l y , t h e r e c o g n i t i o n , t h a t l a n t h a n i d e c a t i o n s c a n be used as s u i t a b l e model c a t i o n s f o r c a l c i u m has been o f g r e a t i n t e r e s t ,
2
because o f t h e v a l u a b l e c o n f o r m a t i o n a l i n f o r m a t i o n , w h i c h can be o b t a i n e d f o r the o r g a n i c l l g a n d from the e f f e c t s o f t h e l a n t h a n i d e c a t i o n s on b o t h t h e c h e m i c a l s h i f t s and r e l a x a t i o n r a t e s o f t h e d i f f e r e n t n u c l e i ^ j ^ . So f a r l i t e r a t u r e d a t a on c o o r d i n a t e d p o l y o x y g e n systems i n w a t e r a r e s c a r c e . I n t h i s t h e s i s b o t h t h e i n f l u e n c e o f t h e c a t i o n on t h e n u c l e i o f t h e l l g a n d as w e l l a s the i n f l u e n c e o f t h e l i g a n d on the c a t i o n have been s t u d i e d by means o f NMR t e c h n i q u e s , _ l . e . ^H, ^ C , and i ^ ' l a NMR. I n t h e s e s t u d i e s a l a r g e range o f c a t i o n - t o - l i g a n d r a t i o s were a p p l i e d . C o m b i n a t i o n o f t h e d a t a o b t a i n e d from d i f f e r e n t measurements g i v e s an e s s e n t i a l l y c o m p l e t e p i c t u r e o f t h e c o o r d i n a t i o n o f t h e c a t i o n .
The m a j o r p a r t o f t h e i n v e s t i g a t i o n s , w h i c h were p e r f o r m e d from 1978 t o 1982 have been p u b l i s h e d . When a p p r o p r i a t e t h e r e w i l l be r e f e r r e d t o t h e s e p a p e r s . I n C h a p t e r I I t h e r e s u l t s o b t a i n e d by 1 70 d y s p r o s i u m i n d u c e d s h i f t
measurements a r e d e s c r i b e d ? > 8 . The a d v a n t a g e o f 1 70 NMR i s t h e f a c t , t h a t t h e (oxygen) n u c l e u s s t u d i e d i s d i r e c t l y a t t a c h e d t o t h e c a t i o n . The 1 70 NMR measurements have been p e r f o r m e d a t r e l a t i v e l y l o w l i g a n d c o n c e n t r a t i o n s i n w a t e r . T h e r e f o r e , t h e use o f ^ O - e n r i c h e d compounds was r e q u i r e d . I n o r d e r t o o b t a i n l ^ C — e n r i c h e d m a t e r i a l s a number o f ^ O - e n r i c h e d p r o c e d u r e s were d e v e l o p e d and a p p l i e d ( C h a p t e r I I I ) . Of t h e l a n t h a n i d e c a t i o n s ^-^~La i s most f a v o u r a b l e f o r o b s e r v a t i o n by NMR. I n f a c t i t i s t h e o n l y l a n t h a n i d e c a t i o n o b s e r v e d i n s o l u t i o n by NMR so f a r . The i n f l u e n c e o f a number o f ( h y d r o x y ) c a r b o x y l a t e s on t h e ^-^La. r e s o n a n c e i s r e p o r t e d i n C h a p t e r i v ' .
I n C h a p t e r V the r e s u l t s o b t a i n e d from 1 3C r e l a x a t i o n r a t e measurements on t h e 13c n u c l e i o f t h e l i g a n d s a r e d e s c r i b e d 1°. I n t h i s s t u d y g a d o l i n i u m ( I I I ) i s t h e l a n t h a n i d e c a t i o n o f c h o i c e .
( C a r b o x y m e t h o x y ) s u c c i n a t e (CMOS), u n t i l r e c e n t l y a p o t e n t i a l c a n d i d a t e f o r u s e i n d e t e r g e n t s a s a phosphate s u b s t i t u t e , has been s u b j e c t o f an e x t e n s i v e s t u d y " , i n w h i c h a l l NMR t e c h n i q u e s , w h i c h a r e d i s c u s s e d i n t h i s t h e s i s have been a p p l i e d ( C h a p t e r V I ) . For t h e c o m p l e t e a s s i g n m e n t o f t h e *H NMR s p e c t r u m o f CMOS s p e c i f i c l a b e l e d CMOS was s y n t h e s i z e d . I n t h i s s y n t h e s i s t h e c o n f i g u r a t i o n o f t h e i n t e r m e d i a t e ( E ) - 2 - ( c a r b o x y m e t h o x y ) ( 3 -2H ) m a l e i c a c i d has been d e t e r m i n e d by X - r a y a n a l y s i s1 2 ( C h a p t e r V I I ) . C h a p t e r V I I I d e a l s w i t h the c h i r a l i n t e r a c t i o n s o f t h e e u r o p i u m ( I I I ) complex of t h e ( S ) - e n a n t i o m e r o f CMOS w i t h some o t h e r p o l y c a r b o x y l a t e s1 3_
R e f e r e n c e s
1. R.H. Wasserman, R.A. C o r r a d i n o , E. C a r a f o l i , R.H. K r e t s i n g e r , D.H. MacLennan and F.L. S i e g e l , " C a l c i u m B i n d i n g P r o t e i n s and C a l c i u m F u n c t i o n " , E l s e v i e r , New Y o r k , 1977.
2. J.R. N o o i , Chemisch Weekblad, 1972, 8 December,11. 3. M.M. C r u t c h f i e l d , J . Am. O i l Chemists Soc. _55, 58 ( 1 9 7 8 ) .
4. S. F o r s S n and B. Lindman, Ann. Rep. NMR S p e c t r o s c . 11A, 183 ( 1 9 8 1 ) . 5. J . Reuben, P r o g . N u c l . Magn. R e s . S p e c t r . _9_, 1 ( 1975).
6. J.A. P e t e r s and A.P.G. Kieboom, R e e l . T r a v . Chim. Pays-Bas 103, 1 ( 1 9 8 4 ) .
7. A.P.G. Kieboom, J.M. v a n d e r Toorn, J.A. P e t e r s , W.M.M.J. BovSe, A. Sinnema, C.A.M. V i j v e r b e r g and H. v a n Bekkum, R e e l . T r a v . Chim. Pays-Bas 97, 247 ( 1 9 7 8 ) .
8. C.A.M. V i j v e r b e r g , J.A. P e t e r s , A.P.G. Kieboom and H. v a n Bekkum, R e e l . T r a v . Chim. Pays-Bas 9 9 , 403 ( 1 9 8 0 ) .
9. C.A.M. V i j v e r b e r g , J.A. P e t e r s , A.P.G. Kieboom and H. v a n Bekkum, R e e l . T r a v . Chim. Pays-Bas _99_, 287 ( 1980).
10. A.P.G. Kieboom, C.A.M. V i j v e r b e r g , J.A. P e t e r s and H. v a n Bekkum, R e e l . T r a v . Chim. Pays-Bas _96_, 315 ( 1977).
11. C.A.M. V i j v e r b e r g , J.A. P e t e r s , W.M.M.J. BovSe, H. V r o o n , A.P.G. Kieboom and H. v a n Bekkum, R e e l . T r a v . Chim. Pays-Bas 102, 255 ( 1983).
12. H. v a n K o n i n g s v e l d , C.A.M. V i j v e r b e r g and J.C. J a n s e n , C r y s t . S t r u c t . Comm. _ U , 793 ( 1982).
13. J.A. P e t e r s , C.A.M. V i j v e r b e r g , A.P.G. Kieboom and H. v a n Bekkum, T e t r a h e d r o n L e t t . _24_, 3141 ( 1983).
4 I I
A STUDY OF DYSPROSIUM(III) HYDROXY- AND ETHERCARBOXYLATE COMPLEXES IN AQUEOUS MEDIUM USING LANTHANIDE INDUCED OXYGEN-17 NMR SHIFTS
A b s t r a c t
The c o m p l e x a t i o n of d y s p r o s i u m ( I I I ) , as a model c a t i o n f o r c a l c i u m ( I I ) , w i t h a s e r i e s of l70 - e n r i c h e d h y d r o x y - and e t h e r c a r b o x y l a t e s i n aqueous medium, has been s t u d i e d by *70 NMR s p e c t r o s c o p y . A c e t a t e , 3 - h y d r o x y b u t y r a t e , g l y c o l a t e , g l y c e r a t e , 3 - h y d r o x y g l u t a r a t e , m a l a t e , c i t r a t e , and e t h o x y a c e t a t e show f a s t l i g a n d exchange on the 1 70 NMR time s c a l e a t 73 °C. The D y ( I I I ) - i n d u c e d i 70 s h i f t s of b o t h the l i g a n d and the w a t e r , w h i c h a r e m a i n l y due t o c o n t a c t i n t e r a c t i o n , p r o v i d e v a l u a b l e i n f o r m a t i o n on the c o m p l e x a t i o n s i t e s of the l i g a n d s as w e l l as on the number of c o o r d i n a t e d w a t e r s i n the c o m p l e x e s . The r e s u l t s p o i n t t o a r a t h e r c o n s t a n t ^70 c o n t a c t s h i f t of around 1700 ppm upon the f o r m a t i o n of D y ( I I I ) - 0 bonds. On the o t h e r hand, o x y d i a c e t a t e (ODA), e t h y l e n e g l y c o l d i a c e t a t e (EGDA), ( c a r b o x y m e t h o x y ) s u c c i n a t e (CMOS), and
n i t r i l o t r i a c e t a t e (NTA) show s l o w l i g a n d exchange on t h e 1 70 NMR t i m e s c a l e a t 73 °C. I n t h e s e c a s e s - w i t h s t i l l f a s t w a t e r exchange - the D y ( I I I ) - i n d u c e d s h i f t of t h e ^7o w a t e r r e s o n a n c e p r o v i d e s i n f o r m a t i o n on the s t o i c h i o m e t r y o f t h e c o m p l e x e s , _i^e_. the number of c o o r d i n a t e d w a t e r s and the number of
l i g a n d s .
I n t r o d u c t i o n
C o m p l e x a t i o n phenomena of p o l y o x y g e n compounds w i t h c a l c i u m ( I I ) i n aqueous medium a r e of i n t e r e s t not o n l y because of the e s s e n t i a l r o l e p l a y e d by C a ( I I ) i n the r e g u l a t i o n of b i o l o g i c a l p r o c e s s e s but a l s o i n the s e a r c h f o r s u i t a b l e phosphate s u b s t i t u t e s i n d e t e r g e n t f o r m u l a t i o n s . I n a d d i t i o n t o our *H and *3C NMR s p e c t r o s c o p i c s t u d i e s i n t h i s f l e l d ^ we now p r e s e n t r e s u l t s based on the
use of 1 70 NMR as the a n a l y t i c a l t o o l2. The use of 1 70 NMR i n the s t u d y of c a t i o n c o m p l e x a t i o n b e h a v i o u r of oxygen compounds has the advantage t h a t t h e n u c l e u s s t u d i e d i s d i r e c t l y a t t a c h e d t o the c a t i o n .
The oxygen i s o t o p e 1 70 has a n a t u r a l abundance of o n l y 0.037%, an NMR
s e n s i t i v i t y of 2.9 x 1 0- 2 ( r e l a t i v e t o hydrogen) and a n u c l e a r s p i n o f 5/2. As a consequence of the e l e c t r i c q u a d r u p o l e moment3, the l i n e w i d t h of the ^70 r e s o n a n c e s i g n a l s i s dominated by q u a d r u p o l e r e l a x a t i o n . T h i s r e l a x a t i o n depends on the ( m o l e c u l a r ) r o t a t i o n a l c o r r e l a t i o n t i m e w h i c h i n t u r n i s c o r r e l a t e d t o s o l u t i o n v i s c o s i t y ^ . To be a b l e t o measure 170 r e s o n a n c e s o f oxygen c o n t a i n i n g compounds i n w a t e r , l70 - e n r i c h m e n t appeared t o be n e c e s s a r y . The l7C — e n r i c h m e n t p r o c e d u r e s used a r e d e s c r i b e d i n d e t a i l i n c h a p t e r I I I . C a ( I I ) d i d not i n d u c e any s h i f t of the c a r b o x y l a t e 1 70 r e s o n a n c e2. T h e r e f o r e , i n s t e a d of C a ( I I ) , w h i c h i s d i a m a g n e t i c , a p a r a m a g n e t i c l a n t h a n i d e ( I I I ) c a t i o n was u s e d . The use of L n ( I I I ) c a t i o n s as probes f o r C a ( I I ) can be j u s t i f i e d by
the f o l l o w i n g arguments:
( i ) the i o n i c r a d i u s of C a ( I I ) (0.99 A) i s w e l l w i t h i n the range of i o n i c r a d i i of the L n ( I I I ) (1.06 A - 0.85 A ) ;
( i i ) L n ( I I I ) can r e p l a c e C a ( I I ) i n p r o t e i n s ^ > 5) sometimes r e s u l t i n g i n a c o n c o m i t a n t enhancement of the b i o l o g i c a l a c t i v i t y ^ ;
( i i i ) m o l e c u l a r s t r u c t u r e s t u d i e s on the C a ( I I ) c o n t a i n i n g p r o t e i n t h e r m o l y s i n and i t s L n ( I I I ) a n a l o g u e s7 and on the C a ( I I ) and L n ( I I I ) s a l t s of the a m i n o c a r b o x y l a t e s E D T A8 - 1 1, n i t r i l o t r i a c e t a t e ( N T A ) 8 , 12 -1 4 a n d t t l e ether c a r b o x y l a t e o x y d i a c e t a t e (ODA)15-17 r e v e a l t h a t C a ( I I ) and L n ( I I I ) c a t i o n s c o o r d i n a t e w i t h the same s e t of donor atoms of the l i g a n d s . To t e s t the a p p l i c a b i l i t y of c a t i o n i n d u c e d 1 70 s h i f t s , the c o m p l e x a t i o n of d y s p r o s i u m ( I I I ) w i t h a s e r i e s o f 1 70 - e n r i c h e d sodium h y d r o x y - and
e t h e r c a r b o x y l a t e s i n aqueous medium has been i n v e s t i g a t e d . D y ( I I I ) , w i t h i o n i c r a d i u s 0.91 A, was chosen as the model c a t i o n f o r C a ( I I ) because t h i s L n ( I I I ) c a t i o n i n d u c e d , by f a r , the l a r g e s t ^70 s h i f t s ^ , 1 9 .
Approach t o d a t a a n a l y s i s
O r i g i n of i n d u c e d s h i f t s
G e n e r a l l y , the l a n t h a n i d e ( I I I ) - i n d u c e d s h i f t ( L I S , A) f o r a n u c l e u s , r e l a t i v e t o i t s d i a m a g n e t i c s t a t e i n an a x i a l l y symmetric complex a t a g i v e n
t e m p e r a t u r e , can be e x p r e s s e d as a sum of the c o n t a c t2^ and d i p o l a r2! c o n t r i b u t i o n s :
6 A = A . <S > + G . D ( 1 ) z where A i s t h e e l e c t r o n - n u c l e a r h y p e r f i n e c o u p l i n g c o n s t a n t , <S_> i s t h e p r o j e c t i o n o f t h e t o t a l e l e c t r o n s p i n m a g n e t i z a t i o n on t h e d i r e c t i o n o f t h e e x t e r n a l m a g n e t i c f i e l d , G i s t h e g e o m e t r i c a l f u n c t i o n (3 c o s2 8 - l ) / r 3 , and D i s a c o n s t a n t f o r a g i v e n l a n t h a n i d e . The r e l a t i v e v a l u e s o f <SZ> and o f D have been t a b u l a t e d by G o l d i n g and H a l t o n2^and by B l e a n e y e t a l .22,
r e s p e c t i v e l y . The v a l u e o f A and t h e <SZ>/D r a t i o o f D y ( I I I ) a r e r e l a t i v e l y h i g h2 3, s o , t h e o r e t i c a l l y , a l a r g e c o n t a c t c o n t r i b u t i o n t o t h e o b s e r v e d s h i f t i s e x p e c t e d . D y ( I I I ) i n d u c e d s h i f t s ( D y l S ) o f t h e 1 70 r e s o n a n c e s a r e i n d e e d p r e d o m i n a n t l y o f c o n t a c t o r i g i n2"1^ . The c o n t r i b u t i o n o f both p s e u d o - c o n t a c t and d i a m a g n e t i c s h i f t s may be n e g l e c t e d and so e q u a t i o n 1 i s r e d u c e d t o :
A - A . <Sz> ( 2 )
F a s t l i g a n d exchange
Under c o n d i t i o n s o f f a s t l i g a n d exchange on t h e NMR time s c a l e t h e o b s e r v e d L I S (A) i s a c o n c e n t r a t i o n - w e i g h t e d average o f t h e s h i f t s o f t h e i n d i v i d u a l s p e c i e s i n s o l u t i o n : a =
T l T
• * n i 'c i •A i (3) o 1=1 where [ L ]Q j .s t h e t o t a l l i g a n d c o n c e n t r a t i o n , n^ i s t h e number o f l i g a n d s i n a g i v e n complex, Cj[ i s t h e c o n c e n t r a t i o n o f s p e c i e s i , A^ i s t h e bound s h i f t o r c h e m i c a l s h i f t ( r e l a t i v e t o i t s d i a m a g n e t i c s t a t e ) o f s p e c i e s i , and N i s t h e number o f d i f f e r e n t t y p e s o f complexes p r e s e n t . R e u b e n2^ has shown t h a t f o r the d e s c r i p t i o n o f L n ( I I I ) - i n d u c e d s h i f t s i n an aqueous s o l u t i o n o f a c e t a t e a t w o - s t e p e q u i l i b r i u m model i s r e q u i r e d . P r e v i o u s l y , we have shown1 t h a t a number o f h y d r o x y c a r b o x y l a t e s c o o r d i n a t e i n a b i - o r t r i d e n t a t e f a s h i o n . I t may be a n t i c i p a t e d , t h e r e f o r e , t h a t t h e L n ( I I I ) complexes i n t h e p r e s e n t s t u d y c o n t a i n e i t h e r one, two o r t h r e e o r g a n i c l i g a n d s . T h i s i s s u p p o r t e d byc r y s t a l l o g r a p h i c d a t a o f some o f t h e s e c o m p l e x e s . Thus, depending on t h e number o f l i g a n d s ( 4 ) , (5) and/or (6) a r e r e q u i r e d t o d e s c r i b e t h e o b s e r v e d s h i f t s . K j , K2 and K3 a r e t h e e q u i l i b r i u m c o n s t a n t s and A j , A2 and A3 a r e t h e bound s h i f t s o f t h e complexes LnL, LnL2 and LnL3> r e s p e c t i v e l y .
LnL + L :LnL (K , A„) 2 2 2
L n L2 + L k a L n L3 ( K3 > A )
(5)
( 6 )
A j , A2 and A3 a r e i n t r i n s i c f u n c t i o n s of the LnL, L n L2 and LnL3 s p e c i e s and a r e r e l a t e d d i r e c t l y t o the o b s e r v e d i n i t i a l s l o p e (X) o f
a A v e r s u s p ( [ L n ]Q/ [ L ] ) p l o t a t c o n s t a n t [ L ]0, where [ L n ]Q i s the t o t a l m o l a r L n ( I I I ) c o n c e n t r a t i o n and [ L ]Q i s the t o t a l l i g a n d m o l a r i t y . I f [ L ]0 »
[ L n ]0 the i n i t i a l s l o p e , X, i n a t w o - s t e p e q u i l i b r i u m model (LnL and LnL2) ^s a p p r o x i m a t e l y ^;
6(A) A
X = - + 2 . A (7) 6(p) [L] . K,
o L
I f Ko i s v e r y s m a l l b o t h terms i n t h e eqn. 7 a r e r e q u i r e d . However, when K2 i s l a r g e , the i n i t i a l s l o p e , X, i s s i m p l y l.h^. A n a l o g o u s l y , i n a t h r e e - s t e p e q u i l i b r i u m model the i n i t i a l s l o p e X i s g i v e n by:
6(A) A 2 . A
X - = i — ^ + ± + 3 . A ( 8 )
6(p) K.KJU K,[L]
2 3 o j o
When K3 i s l a r g e the f i r s t two terms (on the r i g h t hand s i d e of eqn. 8) can be n e g l e c t e d and so the i n i t i a l s l o p e , X, a t s m a l l p v a l u e s , o f a p l o t
of A v e r s u s p i s 3.A^.
In t h e p r e s e n t s t u d y t h e D y ( I I I ) - i n d u c e d s h i f t s ( D y l S ) of t h e 1 70 r e s o n a n c e s were measured a t low D y ( I I I ) t o l i g a n d r a t i o s (p < 0.1) and so the c o n d i t i o n
[ L ]0 » [ L n ]0 i s a l w a y s f u l f i l l e d . In g e n e r a l K2 and K3 are l a r g e and so as a good a p p r o x i m a t i o n the i n i t i a l s l o p e of a D y l S v e r s u s p p l o t i n a two- o r t h r e e - s t e p e q u i l i b r i u m model i s 2.A^ o r 3.A^, r e s p e c t i v e l y . S i n c e t h e D y l S o f the ! ' 0 resonances are mainly of c o n t a c t o r i g i n , we f u r t h e r assume t h a t the bound s h i f t s of the i n d i v i d u a l complexes a r e about the same:
A j = A^ = A j ^ and A^ = A^ = A^ = f o r a two- and t h r e e - s t e p mechanism, r e s p e c t i v e l y .
Slow l i g a n d exchange
8
l i g a n d c o u l d be o b s e r v e d . P r o b a b l y , because o f e x t e n s i v e l i n e b r o a d e n i n g the 170 r e s o n a n c e s of the D y ( I I I ) complexes o f t h e l i g a n d were u n o b s e r v a b l e . However, t h e w a t e r exchange i n t h e s e systems was s t i l l f a s t .
Water exchange
So f a r , t h e o b s e r v e d D y l S o f t h e ^70 r e s o n a n c e s were d i s c u s s e d i n terms o f t h e bound s h i f t s of t h e complexes formed. Now t h e DylS o f t h e "q wat e r r e s o n a n c e i s c o n s i d e r e d . I n t h e D y ( I I I ) - a q u o complex and i n mixed D y ( I I I ) complexes water exchange i s f a s t . I n the absence o f o t h e r l i g a n d s n i n e w a t e r m o l e c u l e s a r e c o o r d i n a t e d t o D y ( I I I ) i n t h e f i r s t c o o r d i n a t i o n s p h e r e2^- 2^ . in t h a t c a s e , t h e DylS o f t h e l?o w a t e r r e s o n a n c e , e x t r a p o l a t e d t o [ D y ( I I I ) ] = 1 a t 73 °C, was found t o be 304 ppm t o h i g h f i e l d . In p r i n c i p l e , n i n e bound s h i f t s o f the d i f f e r e n t D y ( I I I ) - a q u o c o m p l e x e s , A^, A^ Ag, s h o u l d be t a k e n i n t o a c c o u n t , b u t as an a p p r o x i m a t i o n t h e v a l u e o f t h e i n d u c e d *70 NMR s h i f t of a bound w a t e r i s assumed t o be e s s e n t i a l l y i n d e p e n d e n t of the number and n a t u r e of o t h e r l i g a n d s p r e s e n t around the D y ( I I I ) c a t i o n . T h e r e f o r e , f o r each bound w a t e r t h e o v e r a l l w a t e r r e s o n a n c e s h i f t s 304/9 = 33.8 ppm ( a t [ D y ( I I I ) ] = 1 a t 73 °C).
Complex s t o i c h i o m e t r y
F u r t h e r m o r e , t h e c o o r d i n a t i o n number o f D y ( I I I ) i n o t h e r o r mixed complexes i s assumed t o have a c o n s t a n t v a l u e o f n i n e . The number of bound w a t e r s (q) i n t h e D y ( I I I ) complexes w i t h t h e g e n e r a l s t r u c t u r e D y Lp( H 2 0 ) q , i n w h i c h L denotes an o r g a n i c l i g a n d , can now be c a l c u l a t e d by d i v i d i n g t h e D y l S / p o f the w a t e r r e s o n a n c e (^„ „) i n the p r e s e n c e of a l i g a n d by 3 3 . 8 . [ L ]0. The r e m a i n i n g c o o r d i n a t i o n p o s i t i o n s of t h e D y ( I I I ) c a t i o n a r e o c c u p i e d by an o r g a n i c l i g a n d and hence t h e s t o i c h i o m e t r y , i n c l u d i n g t h e number o f w a t e r s o f t h e D y ( I I I ) complexes i n w a t e r , can be e v a l u a t e d . R e s u l t s and d i s c u s s i o n 1 70 c h e m i c a l s h i f t s V a r i o u s ^70 c h e m i c a l s h i f t d a t a have been r e p o r t e d i n t h e l i t e r a t u r e 3 0f i n c l u d i n g n a t u r a l - a b u n d a n c e *70 NMR of m o n o s a c c h a r i d e s i n aqueous medium^!. I n T a b l e I t h e c h e m i c a l s h i f t s and l i n e - w i d t h s of the 1 70 r e s o n a n c e s o f o u r s e r i e s o f sodium h y d r o x y - and e t h e r c a r b o x y l a t e s i n aqueous medium a r e summarized. I t may be n o t e d t h a t t h e use o f D2O i n s t e a d o f H£0 had no i n f l u e n c e on t h e 170 c h e m i c a l s h i f t s i . e . no i s o t o p e s o l v e n t e f f e c t was
T a b l e I . C h e m i c a l s h i f t s3 and l i n e w i d t h s " o f c a r b o x y l a t e , h y d r o x y - and e t h e r 170 r e s o n a n c e s . Compound C h e m i c a l s h i f t (ppm) L i n e w i d t h ( H z ) C a r b o x y l a t e s a c e t a t e 284 m a l o n a t e 282 110 s u c c i n a t e 277 150 1 , 2 , 3 - p r o p a n e t r i c a r b o x y l a t e 2 7 8e 280 g l u t a r a t e 279 165 n i t r i l o t r i a c e t a t e 275 240 H y d r o x y c a r b o x y l a t e sd C00 OH COO OH g l y c o l a t e 269 0 65 l a c t a t e0 263 — 90 g l y c e r a t e 271 18 (a-OH) 95 155 (a-OH) 0 (S-OH) 3 - h y d r o x y b u t y r a t ec 283 36 140 150 t a r t r o n a t ec 266 — 100 3 - h y d r o x y g l u t a r a t e 285 30 185 225 m a l a t e (HO-C-COO-) 267 25 140 155 m a l a t e (-CH2COO-) 284 — 135 c i t r a t e (HO-C-COO-) 264 37 230 340 c i t r a t e (-CH2C00-) 287 — 220 E t h e r c a r b o x y l a t e sd COO 0 COO 0 -o x y d i a c e t a t e ( 0 D A )c 272 0 200 e t h o x y a c e t a t e 273 13 120 250 ( c a r b o x y m e t h o x y ) s u c c i n a t e ( C M 0 S )c 2 7 2e -- 380 e t h y l e n e g l y c o l d i a c e t a t e (EGDA) 272 0 180 R e l a t i v e t o w a t e r ; + 3 ppm. b At h a l f - h e i g h t ; + 25 Hz. c As t h e sodium s a l t (0.35 M) i n H2o a t 73 °C and a t 13.56 MHz. d As t h e sodium s a l t (0.35 M) i n D20 a t 73 °C and a t 27.12 MHz, u n l e s s o t h e r w i s e s t a t e d . e C a r b o x y l a t e s i g n a l s c o i n c i d e .
10
o b s e r v e d . For convenience,- a l l complexes s t u d i e d w i l l be d e n o t e d as. $ r8 DyLp(H20)q, i r r e s p e c t i v e as t o whether H2O o r D2O was the s o l v e n t a p p l i e d . A c c o r d i n g t o t h e i r c a r b o x y l a t e *70 c h e m i c a l s h i f t s a t 73 °C the c a r b o x y l a t e s can be d i v i d e d i n t o two g r o u p s : a - a l k o x y - and a-hydroxy c a r b o x y l a t e s w i t h -a c h e m i c a l s h i f t range of 263-273 ppm and c a r b o x y l a t e s w i t h o u t an a - a l k o x y o r a-hydroxy group w i t h a w i t h a c h e m i c a l s h i f t range o f 274-287 ppm (re-lat±y& w a t e r ) . T h i s d i f f e r e n c e e n a b l e s us t o d i s t i n g u i s h between the two t y p e s o f c a r b o x y l a t e s . The l i n e w i d t h s were found t o d e c r e a s e w i t h i n c r e a s i n g
t e m p e r a t u r e because of d e c r e a s i n g t u m b l i n g t i m e s of the c a r b o x y l a t e a n i o n s . For t h a t r e a s o n , the 170 NMR measurements have been p e r f o r m e d a t 73 °C. C o n t r a r y t o p r e v i o u s2 measurements a t 35 °C, d i s t i n c t 1?0 c a r b o x y l a t e r e s o n a n c e s were o b s e r v e d f o r the two t y p e s of c a r b o x y l a t e groups of b o t h c i t r a t e and m a l a t e a t 73 °C ( s e e F i g . 1 ) . A —I I I I I I I 4 0 0 2 0 0 0 - 2 0 0 - 4 0 0 ppm ~ r - 4 0 0 ppm F i g . 1. 27.12 MHz 1 70 NMR s p e c t r a of ( a ) Na3 c i t r a t e and (b) N a2 m a l a t e ; 0.3! M i n D20 a t 73 °C; e n r i c h m e n t of the c a r b o x y l a t e and h y d r o x y ! 0
F a s t l l g a n d exchange
A d d i t i o n of D y ( I I I ) c h l o r i d e t o aqueous s o l u t i o n s (0.35 M) o f the Na s a l t s of a c e t a t e , g l y c o l a t e , g l y c e r a t e , 3 - h y d r o x y b u t y r a t e , 3 - h y d r o x y g l u t a r a t e , raalate, c i t r a t e o r e t h o x y a c e t a t e a t 73 °C r e s u l t e d i n a s h i f t t o h i g h f i e l d f o r b o t h t h e 17o r e s o n a n c e s of the l i g a n d and t h e ^0 w a t e r r e s o n a n c e . F o r t h e s e compounds the a v e r a g e s p e c t r a of the f r e e and complexed a n i o n s were o b s e r v e d , i . e . c o m p l e x a t i o n and d e c o m p l e x a t i o n a r e f a s t on the 170 NMR t i m e s c a l e . The D y ( I I I ) i n d u c e d s h i f t s ( D y l S ) of the c a r b o x y l a t e and h y d r o x y l r e s o n a n c e s as a f u n c t i o n of the m o l a r r a t i o D y ( I I I ) / l i g a n d (p) y i e l d e d s t r a i g h t l i n e s p a s s i n g t h r o u g h the o r i g i n , as shown i n F i g . 2 f o r a c e t a t e , g l y c o l a t e , and 3-hydroxy g l u t a r a t e . T h i s was a l s o found t o be the c a s e f o r the i n d u c e d w a t e r s h i f t s .
F i g . 2. D y ( I I I ) i n d u c e d s h i f t s ( D y l S ) of the c a r b o x y l a t e and h y d r o x y l i c 170 r e s o n a n c e s of a c e t a t e ( A ) , 3 - h y d r o x y g l u t a r a t e (C00~,»; OH, 9 ) and g l y c o l a t e (COO-, • ; OH, • ) v e r s u s the m o l a r r a t i o D y ( I I I ) / ( h y d r o x y ) -c a r b o x y l a t e (p) i n D 20 a t 27.12 MHz and 73 °C; p o s i t i v e DylS i n d i c a t e u p f i e l d s h i f t s ; [ ( h y d r o x y ) c a r b o x y l a t e ] = 0.35 M.
The o b s e r v e d s l o p e s of the s t r a i g h t l i n e s [X(COO), X(0H), and X(H2°)1 are g i v e n i n T a b l e I I .
I n o r d e r t o e v a l u a t e the number of l i g a n d s (p) i n the DyLp(H20)q complexes the number of bound w a t e r s (q) was c a l c u l a t e d , as o u t l i n e d i n t h e a p p r o a c h t o d a t a a n a l y s i s .
I f i t i s assumed t h a t t h e c o o r d i n a t i o n number of D y ( I I I ) has a c o n s t a n t v a l u e of n i n e , t h e r e a r e (9 - q) c o o r d i n a t i o n p o s i t i o n s l e f t f o r the o r g a n i c l i g a n d . The number of donor atoms i n the l i g a n d s ( d ) , o b t a i n e d from p r e v i o u s ^H and 13c NMR s t u d i e s , was t h e n used t o c a l c u l a t e the number of l i g a n d s i n t h e f i r s t c o o r d i n a t i o n s p h e r e of D y ( I I I ) : p = (9 - q ) / d .
12 T a b l e I I . E x p e r i m e n t a l DyIS/p v a l u e s o f t h e c a r b o x y l a t e [ X ( C O O ) ] , h y d r o x y l [ X ( O H ) ] and w a t e r [ X ( H20 ) 1 170 r e s o n a n c e s3. L i g a n d ( L )b X ( C O O )C X ( O H )C X ( H2o )c a c e t a t e 1 7 6 5 — 5 0 g l y c o l a t e 2 2 8 5 4 6 4 5 2 8 g l y c e r a t e ( H C - C - C O O - ) 2 4 8 5 5 0 4 5 3 5 g l y c e r a t e ( - C H2o h ) — 4 6 0 3 5 3 - h y d r o x y b u t y r a t e 1 9 3 5 6 0 0 4 6 3 - h y d r o x y g l u t a r a t e 1 0 2 0 1 0 2 0 4 2 m a l a t e ( H O - C - C O O-) 1 3 4 5 2 6 8 5 1 8 m a l a t e ( - C H2C O O ~ ) 1 4 9 0 — 1 8 c i t r a t e ( H O - C - C O O-) 1 3 8 0 2 3 5 5 2 3 c i t r a t e ( - C H2C 0 0 ~ ) 9 9 0 — 2 3 EGDA 5 6 0 — 1 0 a E x t r a p o l a t e d t o p = 1; u p f l e l d i n d u c e d s h i f t s a r e d e n o t e d p o s i t i v e . b As t h e i r Na s a l t s , 0 . 3 5 M i n D20 a t 7 3 °C. c C a l c u l a t e d a c c o r d i n g t o t h e l e a s t s q u a r e s method w i t h c o r r e l a t i o n c o e f f i c i e n t s b e t t e r t h a n 0 . 9 9 . On t h e b a s i s o f t h e p v a l u e s and l i t e r a t u r e d a t a c o n c e r n i n g t h e c o m p l e x a t i o n of t h e s e l i g a n d s a d e c i s i o n c a n be made as t o t h e p r e s e n c e o f two o r t h r e e o r g a n i c l i g a n d s i n t h e D y ( I I I ) complexes ( T a b l e I I I ) . The r e s u l t f o r a c e t a t e i s i n agreement w i t h t h e f i n d i n g s o f R e u b e n - ^ showed t h a t a t t h e c o n c e n t r a t i o n used i n t h e p r e s e n t s t u d y a t w o - s t e p
mechanism i s v a l i d , w h i c h i n d i c a t e s D y ( O A c ) 2 ( H 2 0 ) T t o be t h e main s p e c i e s . The e x p e r i m e n t a l d a t a i n d i c a t e t h a t g l y c o l a t e and g l y c e r a t e form 3 : 1 complexes w i t h D y ( I I I ) . 3 - h y d r o x y b u t y r a t e , 3 - h y d r o x y g l u t a r a t e , m a l a t e and c i t r a t e and
EGDA form 2 : 1 c o m p l e x e s .
The ^0 bound s h i f t o f t h e c a r b o x y l a t e group o f a l i g a n d c a n be d e f i n e d as t h e a v e r a g e D y l S o f t h e oxygen atoms o f t h e c a r b o x y l a t e group o f t h i s l i g a n d . As shown b e f o r e1, t h e c a r b o x y l a t e group o f g l y c o l a t e c o o r d i n a t e s t o D y ( I I I ) i n a monodentate f a s h i o n and so t h e o b s e r v e d DylS o f t h e c a r b o x y l a t e group o f t h i s l i g a n d i s t h e a v e r a g e o f t h e D y l S o f a c o o r d i n a t e d and a n o n - c o o r d i n a t e d oxygen atom.
T a b l e I I I . ^0 bound s h i f t s3 o f c a r b o x y l a t e [X(COO)/p ] and h y d r o x y l g r o u p s [X(OH)/p ] as d e r i v e d f o r t h e D y Lp( H20 ) q c o m p l e x e s . L i g a n d ( L ) qb dc pd X(COO)/p X(OH)/p a c e t a t e 4.2 2 2 880
—
g l y c o l a t e 2.4 2 3 760 1550 g l y c e r a t e (HO-C-COO-) 2.9 2 3 830 1680 g l y c e r a t e (-CH2OH) 2.9 2 3 — 155 3 - h y d r o x y b u t y r a t e 3.9 2 2 965 300 3 - h y d r o x y g l u t a r a t e 3.5 - 2 510 510 m a l a t e (HO-C-COO-) 1.5 3 2 670 1340 m a l a t e (-CH2COO~) 1.5 3 2 745—
c i t r a t e (HO-C-COO-) 1.9 3 2 690 1175 c i t r a t e (-CH2COO~) 1.9 3 2 495—
EGDA 0.8 4 2 280—
a I n ppm; q = X ( H2o ) / ( 3 3 . 8 . [ L ]D) . k C a l c u l a t e d number o f c o o r d i n a t e d w a t e r s ( s e e t e x t ) .c T o t a l number o f c a r b o x y l a t e and h y d r o x y l i c oxygen atoms p e r l i g a n d c o o r d i n a t e d t o d y s p r o s i u m ( I I I ) . d C a l c u l a t e d number o f l i g a n d s ( s e e t e x t ) . Dy HO H2C 1
A l t h o u g h a c e t a t e c o o r d i n a t e s D y ( I I I ) i n a s p e c i a l mode, t h e bound s h i f t has about t h e same v a l u e as t h e bound s h i f t o f g l y c o l a t e . I n t h e case o f
a c e t a t e ^-^C r e l a x a t i o n measurements! showed t h a t t h e c a t i o n i s p o s i t i o n e d on the e x t e n s i o n o f t h e C -C ( c a r b o x y l a t e ) bond:
C H . C
3 \
Dy
S i n c e t h e 13c r e l a x a t i o n measurements g i v e t h e a v e r a g e p o s i t i o n o f t h e c a t i o n , the complex f o r m a t i o n may a l s o be c o n s i d e r e d as a f a s t e q u i l i b r i u m between two i d e n t i c a l complexes as i l l u s t r a t e d b e l o w . O / C H3C Dy C H . C 3 \ Dy
The 1'0 bound s h i f t of the h y d r o x y l group of g l y c o l a t e , i n w h i c h t h e
c a r b o x y l a t e and t h e C-OH groups a r e a l m o s t c o p l a n a r w i t h D y ( I I I ) p o s i t i o n e d i n the same p l a n e3 2» 3 3t ±s t w i c e as l a r g e as the 1 7o bound s h i f t of t h e
c a r b o x y l a t e g r o u p . T h i s i s a l s o t r u e f o r t h e a - h y d r o x y l group o f g l y c e r a t e . A p p a r e n t l y , t h e 1 7o c o n t a c t s h i f t due t o t h e f o r m a t i o n of a D y ( I I I ) - 0 bond seems t o be r a t h e r c o n s t a n t . I n a d d i t i o n , t h e 1 70 bound s h i f t of the oxygen atoms o f w a t e r i n t h e D y ( I I I ) complex, i n t h e absence of o t h e r l i g a n d s was (55.5/9) . 304 = 1875 ppm, w h i c h i s of about the same magnitude as t h e 1 70 bound s h i f t s of t h e a - h y d r o x y l groups o f g l y c o l a t e and g l y c e r a t e . I n
c o n c l u s i o n , the 1 70 c o n t a c t s h i f t i s r a t h e r c o n s t a n t (1700 + 200 ppm). T h i s p r o v i d e s a b a s i s f o r a s t r a i g h t f o r w a r d i n t e r p r e t a t i o n o f the o b s e r v e d I'O bound s h i f t s of t h e i n d i v i d u a l compounds.
I n t e r p r e t a t i o n of 17Q DylS of i n d i v i d u a l compounds
3 - H y d r o x y b u t y r a t e c o o r d i n a t e s p r e d o m i n a n t l y w i t h i t s c a r b o x y l a t e group i n a b i d e n t a t e way. However, t h e 1 70 bound s h i f t o f t h e 8 - h y d r o x y l group i n d i c a t e s a c o n t r i b u t i o n o f about 15% (= ( 3 0 0 / ( 2 . 9 6 5 ) ) . 100) o f a complex i n w h i c h
t h e h y d r o x y l and the c a r b o x y l a t e group ( i n a monodentate way) a r e c o o r d i n a t e d . OH I C H , C C H , C Dy I \ / / \ • \ HO O I I HC C ^CH,' H,C V u 7 O 6 The r e s u l t s f o r g l y c e r a t e c l e a r l y p o i n t t o the s i m u l t a n e o u s c o o r d i n a t i o n o f t h e a - h y d r o x y l and t h e c a r b o x y l a t e group t o D y ( I I I ) , the l a t t e r i n a monodentate way, whereas the 8 - h y d r o x y l group c o n t r i b u t e s f o r o n l y 10% (= ( 1 5 5 / ( 2 . 830)) . 100) t o the c o m p l e x a t i o n o f D y ( I I I ) . Dy Dy
/ I \
/ s ' I \ HO O _ HO I O \ / I OH I HC C H,C I C / \ \ I / \ H O C H , O xc ' C HIn the c a s e of 3 - h y d r o x y g l u t a r a t e a f a s t e q u i l i b r i u m between s e v e r a l complexes may e x i s t as i s shown s c h e m a t i c a l l y below.
C O O COOs COO C O O Dy
~-Dy Cf C Dy ^=-^- C
\ / \ \ / \
COO COO COO COO 9 10 11 12
I n the complexes 9, 10, and 11 t h e c a r b o x y l a t e group c o o r d i n a t e s i n a monodentate f a s h i o n , whereas the c a r b o x y l a t e group of 12 c o o r d i n a t e s i n a b i d e n t a t e way. W i t h a D y ( I I I ) - 0 bound s h i f t of 1700 ppm, t h e r e l a t i v e
i m p o r t a n c e of the complexes can be e s t i m a t e d t o d e c r e a s e i n the o r d e r 12 > 9, 10 > 11.
The e x p e r i m e n t a l d a t a f o r m a l a t e showed t h a t complex 13 p r e d o m i n a t e s , i n w h i c h s i m u l t a n e o u s c o o r d i n a t i o n of the h y d r o x y l and b o t h c a r b o x y l a t e groups o c c u r .
16
As found f o r g l y c o l a t e , t h e 1 70 bound s h i f t o f the h y d r o x y l group i s about t w i c e as l a r g e as t h a t o f b o t h c a r b o x y l a t e g r o u p s .
H 'c \ > ~ V
H C ^ /
coo'
13
The 170 bound s h i f t s o f c i t r a t e may be e x p l a i n e d by a f a s t e q u i l i b r i u m between f o u r complexes (14-17) o f w h i c h 14 and 15 a r e t h e main s p e c i e s , i n a c c o r d a n c e w i t h o u r e a r l i e r r e s u l t s * "2. The e x p e r i m e n t a l d a t a a l s o i n d i c a t e t h e g r e a t e r i m p o r t a n c e o f 16 as compared t o 17. I n t h i s c a s e t h e d i f f e r e n c e i n t h e 1 70 bound s h i f t s o f t h e c a r b o x y l a t e groups i s c l e a r l y a t t r i b u t e d t o t h e s m a l l e r r e s i d e n c e time o f D y ( I I I ) a t one o f t h e - C H 2C 0 0~ g r o u p s . C O ON C O O / \ / H j C
\ g--~?
y"*\ g
,CH2COON C H2C O O K / <=£ H O - C - C O O — D y --=5= O O C - C - S - - - 6 y /NC O o ' / NC O O - - - D y \ / \ / H2C X H2<=x / C H2C O O ' C H j C O O C O O C O O ' ' 16 17 14 15 U n f o r t u n a t e l y , a d d i t i o n o f D y ( I I I ) c h l o r i d e t o an aqueous s o l u t i o n (0.35 M) o f e t h o x y a c e t a t e r e s u l t e d i n p r e c i p i t a t i o n o f D y ( I I I ) e t h o x y a c e t a t e . However, i n t h e p r e s e n c e o f a s m a l l amount o f ODA ([ODA] = 0.008 M and [ e t h o x y a c e t a t e ] = 0.15 M) no p r e c i p i t a t i o n o c c u r r e d and so t h e DylS o f t h e !'0 r e s o n a n c e s o f e t h o x y a c e t a t e c o u l d be measured. The r a t i o o f t h e D y l S o f t h e e t h e r and c a r b o x y l a t e 1 70 r e s o n a n c e s (^ ( - C — ) /A (COO)) was o n l y 0.8. Assuming a c o n s t a n t 1 70 c o n t a c t s h i f t upon t h e f o r m a t i o n o f a D y ( I I I ) - 0 bond, i r r e s p e c t i v e o f t h e n a t u r e o f t h e oxygen atom, t h i s r e s u l t p o i n t s t o a f a s t e q u i l i b r i u m between two c o m p l e x e s , o f w h i c h 18 a p p e a r s t o be t h e main s p e c i e s . Comparison o f t h e s t a b i l i t y c o n s t a n t s3^ o f t h e C a ( I I ) complexes o f a c e t a t e , g l y c o l a t e andr e s p e c t i v e l y , s u p p o r t s t h i s i n t e r p r e t a t i o n . / ^ ' \ C H . C H j O C H . C ^ D y ^ CH,CH,—o" S0 H,C C 2 \ o 18 19
The l o w 1 70 bound s h i f t o f t h e c a r b o x y l a t e groups o f EGDA i n d i c a t e a r e l a t i v e l y s m a l l r e s i d e n c e time o f D y ( I I I ) a t t h e s e c a r b o x y l a t e g r o u p s . U n f o r t u n a t e l y , a d d i t i o n a l i n f o r m a t i o n about t h e c o m p l e x e s , w h i c h may be formed i n aqueous s o l u t i o n , c o u l d n o t be o b t a i n e d , because t h e exchange o f D y ( I I I ) appeared t o be s l o w f o r t h e 170 e t h e r r e s o n a n c e o f EGDA ( v i d e i n f r a ) .
Slow l i g a n d exchange
The 1^0 c a r b o x y l a t e r e s o n a n c e s o f t h e r e l a t i v e l y s t r o n g l y c o m p l e x i n g compounds ODA, CMOS and NTA and t h e 1 70 e t h e r r e s o n a n c e s o f ODA and EGDA d i d n o t show any i n d u c e d s h i f t upon a d d i t i o n o f D y ( I I I ) c h l o r i d e . The i n t e n s i t i e s o f t h e 170 c a r b o x y l a t e r e s o n a n c e s o f ODA, CMOS and NTA, however, were r e d u c e d p r o p o r t i o n a l l y t o t h e amount o f D y ( I I I ) added. A f t e r a d d i t i o n o f s m a l l amounts of D y ( I I I ) t h e l 70 e t h e r r e s o n a n c e s o f ODA and EGDA were s e v e r e l y b r o a d e n e d . O b v i o u s l y , c o m p l e x a t i o n and d e c o m p l e x a t i o n o f D y ( I I I ) i n t h e s e c a s e s a r e s l o w on t h e 170 NMR time s c a l e a t 73 °C, 'i»,e» s e p a r a t e s i g n a l s o c c u r f o r t h e f r e e and complexed l i g a n d s . A t 90 °C t h e l i n e w i d t h o f t h e above m e n t i o n e d 1 70 c a r b o x y l a t e r e s o n a n c e s was i n c r e a s e d s u b s t a n t i a l l y . C l e a r l y , t h e l i g a n d exchange r a t e i s enhanced, r e s u l t i n g i n b r o a d e r ^70 r e s o n a n c e s o f t h e f r e e l i g a n d , b u t i s s t i l l r e l a t i v e l y s l o w on t h e l7o NMR time s c a l e . U n f o r t u n a t e l y , t h e complexed l i g a n d s c o u l d n o t be o b s e r v e d . T h i s i s p r o b a b l y due t o e x t e n s i v e l i n e b r o a d e n i n g o f t h e 1 7o r e s o n a n c e s o f t h e D y ( I I I ) c o m p l e x e s . G f e l l e r and M e r b a c h3^ have shown t h a t t h e NTA exchange f o r a s e r i e s o f L n ( I I I ) - N T A complexes i s s l o w a t 35 °C on t h e NMR time s c a l e . On t h e o t h e r hand, t h e ODA and CMOS exchange were found t o be f a s t a t 35 °C on t h e lB NMR time
s c a l e ^ l j a p p a r e n t l y due t o t h e s m a l l e r c h e m i c a l s h i f t d i f f e r e n c e s between f r e e and complexed l i g a n d s f o r NMR w i t h r e s p e c t t o 170 NMR. These d a t a i n d i c a t e t h a t t h e r a t e o f exchange o f NTA i s s m a l l e r t h a n t h a t o f ODA and CMOS. The w a t e r exchange i n t h e above m e n t i o n e d systems appeared t o be f a s t ; no, o r a r a t h e r s m a l l , i n d u c e d s h i f t o f t h e 1 70 w a t e r r e s o n a n c e was o b s e r v e d a t low p v a l u e s ( F i g . 3 and 4 ) .
18
In t h e c a s e o f ODA t h e o b s e r v e d D y l S o f water i s n o t e w o r t h y : f o r p < 0.3 the 1^0 w a t e r r e s o n a n c e d i d n o t s h i f t a t a l l , whereas f o r p > 0.3 a s h i f t t o h i g h f i e l d o c c u r s t o t h e same e x t e n t as i n the absence o f ODA ( F i g . 3 ) . T h i s
3-p i c t u r e c l e a r l y r e f l e c t s the 3-p r e s e n c e o f t h e 3:1 c o m 3-p l e x , Dy(0DA).j , a t 3-p < 0.3, _i_._e. t h e t h r e e t r i d e n t a t e ODA l i g a n d s p r o h i b i t any c o o r d i n a t i o n o f w a t e r i n a c c o r d a n c e w i t h a c o o r d i n a t i o n number o f n i n e f o r D y ( I I I ) . The b e h a v i o u r o f the 1'0 w a t e r r e s o n a n c e i n t h e case o f NTA and CMOS i s d i f f e r e n t .
A l t h o u g h NTA and CMOS form more s t a b l e D y ( I I I ) c o m p l e x e s , a d d i t i o n o f D y ( I I I ) r e s u l t e d i n a s m a l l s h i f t t o h i g h f i e l d o f t h e *70 w a t e r r e s o n a n c e ( F i g . 4 ) . A p p a r e n t l y , NTA and CMOS a r e i n c a p a b l e o f removing a l l t h e w a t e r s from t h e D y ( I I I ) c a t i o n . A t l o w p v a l u e s t h e r e s u l t s p o i n t t o t h e f o r m a t i o n of DylS a F i g . 3 F i g . 4 F i g . 3. The D y ( I I I ) - i n d u c e d s h i f t s ( D y l S ) o f t h e 1 70 w a t e r r e s o n a n c e i n t h e p r e s e n c e o f o x y d i a c e t a t e (ODA) v e r s u s t h e m o l a r r a t i o D y ( I I I ) / 0 D A ( p ) at 73 "C; [ODA] = 0.35 M. F i g . 4. The D y ( I I I ) - i n d u c e d s h i f t s ( D y l S ) o f t h e 170 w a t e r r e s o n a n c e i n t h e p r e s e n c e o f ( a ) CMOS and (b) NTA v e r s u s t h e m o l a r r a t i o s
[ D y ( N T A )2( H 2 0 ) ] and [Dy(CM0S)2(H20) ] c o m p l e x e s , w h i c h c o r r e s p o n d s t o f o u r donor atoms per l i g a n d . C o n s e q u e n t l y , the NTA and CMOS l i g a n d s c o o r d i n a t e t o D y ( I I I ) i n aqueous s o l u t i o n i n the f o l l o w i n g way:
Dy
2 0
~-o
21
In the case of NTA t h e 1 70 w a t e r s h i f t a t p > 0.5 i s one t h i r d of the v a l u e 3+
e x p e c t e d f o r t h e a d d i t i o n a l f o r m a t i o n of Dy(H20)g . T h i s p o i n t s t o t h e
f o r m a t i o n of a complex w i t h a g r o s s f o r m u l a [ D y ( N T A ) ( H 2 0 ) 3 ln a t p > 0.5, w h i c h 36 may be due t o the t e n d e n c y of NTA t o form d i m e r i z e d hydroxy-NTA complexes and/or t o the f o r m a t i o n of i n t e r m o l e c u l a r a c e t a t e b r i d g e s such as t h o s e found
1 o i n the c r y s t a l s t r u c t u r e of Dy(NTA).2H2° •
C o n c l u s i o n s
The r e s u l t s d e m o n s t r a t e the a p p l i c a b i l i t y of 1 70 NMR s p e c t r o s c o p y t o the s t u d y of c o m p l e x a t i o n phenomena between p o l y o x y g e n compounds and c a t i o n s i n aqueous medium.
The D y ( I I I ) i n d u c e d 1 70 s h i f t s of b o t h the l i g a n d and the w a t e r p r o v i d e v a l u a b l e i n f o r m a t i o n on the c o m p l e x a t i o n s i t e s of the l i g a n d , t h e
s t o i c h i o m e t r y of the D y ( I I I ) complexes formed and the number of c o o r d i n a t e d w a t e r s . The D y l S d a t a s u g g e s t a r a t h e r c o n s t a n t 1 70 c o n t a c t s h i f t upon f o r m a t i o n of D y ( I I I ) - 0 bonds, w h i c h o f f e r s a s t r a i g h t f o r w a r d i n t e r p r e t a t i o n of t h e D y ( I I I ) i n d u c e d *70 s h i f t d a t a i n terms of O - c o o r d i n a t i o n s i t e s of the l i g a n d . E x p e r i m e n t a l The 170 NMR s p e c t r a were r e c o r d e d on e i t h e r a V a r i a n XL-100-15 s p e c t r o m e t e r i n the p u l s e FT mode or on a N i c o l e t NT-200 WB s p e c t r o m e t e r .
20
t o p r o v i d e t h e 13.56 MHz o b s e r v e f r e q u e n c y . ( F o r 10 kHz s p e c t r a l w i d t h 410 d a t a p o i n t s were u s e d ) . The number of t r a n s i e n t s was i n t h e range o f 10^ -2 . 10^ w i t h an a c q u i s i t i o n time o f 0.0-2 s and a p u l s e w i d t h o f 70 ys
( c o r r e s p o n d i n g t o a 90° p u l s e ) . 1 70 c h e m i c a l s h i f t s were measured w i t h r e s p e c t t o t h e 13.56 MHz o b s e r v e f r e q u e n c y . The D y l S o f t h e ^0 r e s o n a n c e o f ^ 0 was c o r r e c t e d f o r t h e DylS o f t h e *H r e s o n a n c e o f H2O, w h i c h was used f o r i n t e r n a l l o c k . T h i s c o r r e c t i o n c o u l d be n e g l e c t e d f o r t h e r e l a t i v e l y l a r g e D y l S o f t h e
c a r b o x y l a t e r e s o n a n c e .
The N i c o l e t NT-200 WB o p e r a t e d a t 27.12 MHz. The number o f t r a n s i e n t s was i n the range 300-2.10^ w i t h an a c q u i s i t i o n time o f 0.04 o r 0.05 s, a p u l s e w i d t h of 35 us ( c o r r e s p o n d i n g t o a 90° p u l s e ) and a s p e c t r a l w i d t h o f 20 o r 27 kHz. The 2H r e s o n a n c e o f D20 was used f o r i n t e r n a l l o c k .
The w a t e r c o n t e n t o f t h e 1 ' 0 - e n r i c h e d sodium c a r b o x y l a t e s was d e t e r m i n e d by 60 MHz XH NMR ( s e e T a b l e I V ) .
T a b l e I V . Moles o f w a t e r p r e s e n t p e r mole o f *70 - e n r i c h e d sodium s a l t .
a c e t a t e 0.3 g l y c o l a t e 1.0 g l y c e r a t e 0.5 3 - h y d r o x y b u t y r a t e 0.0 3 - h y d r o x y g l u t a r a t e 1.8 m a l a t e c i t r a t e EGDA e t h o x y a c e t a t e ODA 1.7 2.6 1.2 0.2 1.9 R e f e r e n c e s
1. A.P.G. Kieboom, C.A.M. V i j v e r b e r g , J.A. P e t e r s and H. v a n Bekkum, R e e l . T r a v . Chim. Pays-Bas 96, 315 ( 1 9 7 7 ) , and r e f e r e n c e s c i t e d t h e r e i n . 2. A.P.G. Kieboom, J.M. v a n d e r T o o r n , J.A. P e t e r s , W.M.M.J. Bovée, A.
Sinnema, C.A.M. V i j v e r b e r g and H. van Bekkum, R e e l . T r a v . Chim. Pays-Bas 97, 247 ( 1 9 7 8 ) ; C.A.M. V i j v e r b e r g , J.A. P e t e r s , A.P.G. Kieboom and H. van Bekkum, R e e l . T r a v . Chim. Pays-Bas 99, 403 ( 1 9 8 0 ) .
3. W.G. K l e m p e r e r , Angew. Chem. 9Q_, 258 ( 1 9 7 8 ) .
4. T.L. B l u n d e l l and J.A. J e n k i n s , Chem. Soc. Rev. _6_, 139 ( 1 9 7 7 ) .
5. " C a l c i u m B i n d i n g P r o t e i n s and C a l c i u m F u n c t i o n " , R.H. Wasserman, R.A. C o r r a d i n o , E. C a r a f o l i , R.H. K r e t s i n g e r , D.H. MacLennan and F.L. S i e g e l , New Y o r k , E l s e v i e r N o r t h - H o l l a n d 1977, pp. 21-28.
6. D.W. D a r n a l l and E.R. Birnbaum, J . B i o l . Chem. 245, 6484 ( 1 9 7 0 ) . 7. B.W. Matthews and L.H. Weaver, B i o c h e m i s t r y J_3, 1719 ( 1 9 7 4 ) .
8. B.L. B a r n e t t and V.A. Uchtman, I n o r g . Chem. _L8_, 2674 ( 1 9 7 9 ) . 9. J . L . H o a r d , Byungkook Lee and M.D. L l n d , J . Am. Chem. Soc. 87, 1612
( 1 9 6 5 ) .
10. M.D. L i n d , Byungkook Lee and J . L . Hoard, J . Am. Chem. Soc. 87, 1611 ( 1 9 6 5 ) .
11. L.R. N a s s i m b e n i , M.R.W. W r i g h t , J.C. van N i e k e r k and P.A. M c C a l l u m , A c t a C r y s t a l l o g r . B 35, 1341 ( 1 9 7 9 ) .
12. L.L. M a r t i n and R.A. J a c o b s o n , I n o r g . Chem. 11, 2785 ( 1 9 7 2 ) . 13. L.L. M a r t i n and R.A. J a c o b s o n , I n o r g . Chem. _U_, 2789 ( 1 9 7 2 ) .
14. C.F. B e l y a e v a , M.A. P o r a i - K o s h i t s and T . I . M a l i n o w s k y , E u r . C r y s t a l l o g r . M e e t i n g 1974, 346.
15. V.A. Uchtman and R.P. O e r t e l , J . Am. Chem. Soc. _9_5, 1802 ( 1 9 7 3 ) . 16. J . A l b e r t s s o n , A c t a Chem. Scand. _22_, 1563 ( 1 9 6 8 ) .
17. I . E l d i n g , A c t a Chem. Scand. A 30, 649 ( 1 9 7 6 ) .
18. W.B. L e w i s , J.A. J a c k s o n , J . F . Lemons and H. Taube, J . Chem. Phys. 36, 694 ( 1 9 6 2 ) .
19. J . Reuben and D. F i a t , J . Chem. Phys. _51_, 4909 ( 1 9 6 9 ) .
20. R.M. G o l d i n g and M.P. H a l t o n , A u s t r . J . Chem. 25_, 2577 ( 1 9 7 2 ) . 21. B. B l e a n e y , J . Magn. Res._8_, 91 ( 1 9 7 2 ) .
22. B. B l e a n e y , C M . Dobson, B.A. L e v i n e , R.B. M a r t i n , R.J.P. W i l l i a m s and A.V. X a v i e r , J . Chem. S o c , Chem. Commun. 1972, 7 9 1 .
23. C.N. R e i l l e y , B.W. Good and R.D. A l l e n d o e r f e r , A n a l . Chem. _48_, 1446 ( 1 9 7 6 ) .
24. J . Reuben and G.A. E l g a v i s h , J . Am. Chem. Soc. _98_, 4755 ( 1 9 7 6 ) .
25. B.L. S h a p i r o and M.D. J o h n s t o n , J r . , J . Am. Chem. S o c . 94, 8185 ( 1 9 7 2 ) . 26. L.O. Morgan, J . Chem. Phys. 38, 2788 ( 1 9 6 3 ) .
27. J . Reuben, B i o c h e m i s t r y 10, 2834 ( 1 9 7 1 ) .
28. Y. Haas and G. S t e i n , J . Phys. Chem. 75_, 3677 ( 1 9 7 1 ) .
29. I . G r e n t h e , G. H e s s l e r and H. O t s , A c t a Chem. Scand. _27_» 2543 ( 1 9 7 3 ) . 30. See e_.£.
a. H.A. C h r i s t , P. D i e h l , H.R. S c h n e i d e r and H. Dahn, H e l v . Chim. A c t a 44, 865 ( 1 9 6 1 ) ;
b. C. D e l s e t h and J . P . K i n t z i n g e r , H e l v . Chim. A c t a _59_, 466 ( 1 9 7 6 ) ; c. T. Sugawara, Y. Kawada and H. Iwamura, Chem. L e t t . 1978, 1371; d. P.A.J. G o r i n and M. Mazurek, C a r b o h y d r . R e s . 67, 479 ( 1 9 7 8 ) ; e. J.K. C r a n d e l l and M.A. Centeno, J . O r g . Chem. 44, 1183 ( 1 9 7 9 ) ; f . J.K. C r a n d e l l , M.A. Centeno and S. BjSrresen, J . O r g . Chem. 44, 1184
22
31. I . P . G e r o t h a n a s s i s , J . L a u t e r w e i n and N. Sheppard, J . Magn. Res. 48, 431 ( 1 9 8 2 ) .
32. I . G r e n t h e , A c t a Chem. Scand. _23, 1752 ( 1 9 6 9 ) . 33. I . G r e n t h e , A c t a Chem. Scand. 26, 1479 ( 1 9 7 2 ) .
34. A.E. M a r t e l l and R.M. S m i t h , C r i t i c a l S t a b i l i t y C o n s t a n t s , V o l . 3: Other o r g a n i c l i g a n d s 1977, 3, 24, 69.
35. Y. G f e l l e r and A. Merbach, I n o r g . Chem. A c t a 2% 217 ( 1 9 7 8 ) .
36. N . I . Snezhko, L.V. Anan'eva, N . I . P e c h u r o v a , L . I . Martynenko and V . I . S p i t s y n , Russ. J . I n o r g . Chem. 17, 1539 ( 1 9 7 2 ) .
I I I
SYNTHESIS OF 1 70-ENRICHED SODIUM SALTS OF HYDROXY- AND ETHERCARBOXYLATES
A b s t r a c t
For the s t u d y of d y s p r o s i u m ( I I I ) h y d r o x y - and e t h e r c a r b o x y l a t e complexes I n w a t e r by 1 70 NMR s p e c t r o s c o p y a number o f 1 70 - e n r i c h m e n t p r o c e d u r e s have been a p p l i e d .
C a r b o x y l a t e groups were e n r i c h e d e i t h e r by d i r e c t i s o t o p i c oxygen exchange w i t h 1 70 - e n r i c h e d w a t e r u s i n g the c o r r e s p o n d i n g c a r b o x y l l c a c i d s o r by a l k a l i n e h y d r o l y s i s of the c o r r e s p o n d i n g m e t h y l o r e t h y l e s t e r s .
1 70 - e n r i c h m e n t of a l d e h y d e s and k e t o n e s was r e a d i l y a c h i e v e d by a c i d c a t a l y z e d oxygen exchange w i t h l70 - e n r i c h e d w a t e r .
1 70 - e n r i c h m e n t of h y d r o x y l groups was a c h i e v e d by: ( i ) r e a c t i o n o f bromo compounds w i t h 1 70 - e n r i c h e d w a t e r i n the p r e s e n c e of Ag20, ( i i ) a c i d h y d r o l y s i s of d l a z o compounds i n 1 70 - e n r i c h e d w a t e r , ( i i i ) NaBHz, o r L i A l H ^ r e d u c t i o n of l 70 - e n r i c h e d a l d e h y d e s or k e t o n e s , and ( i v ) c y a n o h y d r i n s y n t h e s i s u s i n g l70 - e n r i c h e d k e t o n e .
"^O-enrichment of e t h e r groups was a c h i e v e d by a W i l l i a m s o n s y n t h e s i s u s i n g an 1 70 - e n r i c h e d a l c o h o l or by c a r b o x y m e t h y l a t i o n of an 1 70 - e n r i c h e d a l c o h o l u s i n g e t h y l d i a z o a c e t a t e .
I n t r o d u c t i o n
Of the t h r e e s t a b l e oxygen i s o t o p e s ^ 0 , 170 , and 18o, o n l y 170 can be s t u d i e d by n u c l e a r m a g n e t i c r e s o n a n c e s p e c t r o s c o p y . However, the NMR c h a r a c t e r i s t i c s o f t h i s n u c l e u s a r e r a t h e r u n f a v o u r a b l e : ( i ) t h e n a t u r a l abundance i s 0.037%, ( i i ) the NMR s e n s i t i v i t y i s 2.9 x 1 0- 2 r e l a t i v e t o *H and ( i i i ) the n u c l e a r s p i n i s 5/2. These c h a r a c t e r i s t i c s i n c o m b i n a t i o n w i t h t h e w i s h t o o b t a i n 1 70
- C G
2H 2£=? - CCT
2H - " C O > a
H , 0 *
- C O , R — - — C O , N a
NaOH
2•OH
NaH
— C
—Br
— C — O
—R
OH
B F
3. O E t
2H — C — O R
— C
—Br
H
20
A g
20
— C — O H
X N ,
H
20
H — C — O H
Scheme I . l ^ O - e n r i c h m e n t p r o c e d u r e s usedr e s o n a n c e s at low c o n c e n t r a t i o n s i n w a t e r , r e q u i r e d l70 - e n r i c h m e n t of the compounds s t u d i e d . For the l70 - e n r i c h m e n t p r o c e d u r e s w a t e r c o n t a i n i n g a b o u t 20% 1'0 i s c o m m e r c i a l l y a v a i l a b l e .
Most of the i n v e s t i g a t i o n s of the i s o t o p i c exchange of oxygen d e s c r i b e d i n l i t e r a t u r e r e f e r t o 1^0 l a b e l i n g . However, the p r o c e d u r e s w h i c h have been d e v e l o p e d f o r l ^ O - l a b e l i n g l >2 of o r g a n i c compounds c a n , of c o u r s e , a l s o be a p p l i e d f o r l ^ O - l a b e l i n g . The methods used i n t h i s i n v e s t i g a t i o n f o r 'o-e n r i c h m 'o-e n t of c a r b o x y l a t 'o-e , h y d r o x y l and 'o-e t h 'o-e r oxyg'o-ens ar'o-e summariz'o-ed i n Scheme I .
L a b e l i n g of c a r b o x y l i c a c i d s can be a c h i e v e d by i s o t o p i c oxygen exchange w i t h w a t e r . S i n c e the exchange at room t e m p e r a t u r e i s s l o w , g e n e r a l l y e l e v a t e d t e m p e r a t u r e s (80-90 °C) a r e a p p l i e d . M o r e o v e r , the exchange i s c a t a l y z e d by m i n e r a l a c i d s . Sodium c a r b o x y l a t e s u s u a l l y do not exchange w i t h w a t e r .
I n the case of e s t e r s i s o t o p i c exchange of oxygen competes w i t h h y d r o l y s i s . On the o t h e r hand, the a l k a l i n e h y d r o l y s i s of m e t h y l o r e t h y l e s t e r s can be a p p l i e d t o o b t a i n l a b e l e d a l k a l i s a l t s of c a r b o x y l i c a c i d s .
A p a r t from the exchange of some t e r t i a r y a l c o h o l s3 t the d i r e c t oxygen exchange o f a l c o h o l s i s s l o w and r e q u i r e s extreme c o n d i t i o n s ^1. T h e r e f o r e , l a b e l i n g of the h y d r o x y l group needs s e v e r a l s y n t h e t i c s t e p s .
A l d e h y d e s and k e t o n e s may undergo oxygen exchange r e a d i l y . Both a c i d and base c a t a l y z e d exchange have been o b s e r v e d , but g e n e r a l l y the exchange i s a c i d c a t a l y z e d . The w i d e l y a c c e p t e d mechanism f o r exchange i s the r e v e r s i b l e h y d r a t i o n of the c a r b o n y l g r o u p e- 7.
*70 - e n r i c h m e n t l e v e l s of 5-10% were o b t a i n e d by t h e s e p r o c e d u r e s , or c o m b i n a t i o n s t h e r e o f , as d e s c r i b e d below i n more d e t a i l f o r a number o f p o l y o x y g e n compounds. The p r o c e d u r e s d e s c r i b e the r e a c t i o n s by w h i c h the i n d i c a t e d oxygen atoms were e n r i c h e d . Other oxygen atoms w i t h i n the same compound may a l s o be e n r i c h e d , however, t o a much s m a l l e r e x t e n t , by accompanying exchange r e a c t i o n s .
S y n t h e s i s of ^ O - e n r i c h e d compounds
E t h y l [ 2 - 1 7 p ] g l y c o l a t e ( 1 ) was p r e p a r e d by a c i d i c h y d r o l y s i s of e t h y l
d i a z o a c e t a t e i n l ^ O - e n r i c h e d w a t e r . S m a l l amounts of d i e t h y l [ l70 ] o x y d i a c e t a t e a r e formed by the r e a c t i o n of e t h y l d i a z o a c e t a t e and 1. P u r i f i c a t i o n of 1 was r e a d i l y a c h i e v e d by d i s t i l l a t i o n i n v a c u o .
26 H , 0 * r— H O C H , C O O E t [ 2 , 3 -1 70 ] g l y c e r i c a c i d ( 2 ) was p r e p a r e d by r e a c t i o n o f l ^ C — e n r i c h e d w a t e r and 2 , 3 - d i b r o m o p r o p i o n i c a c i d i n t h e p r e s e n c e o f Ag20« P u r i f i c a t i o n was a c h i e v e d v i a r e p e a t e d c r y s t a l l i z a t i o n of t h e c a l c i u m s a l t of 2. C H , — C H C O O H - - C H , — C H — C O O H I I A9 2 ° J I B r Br * O H OH 2 E t h y l 3 - [i /O l h y d r o x y b u t v r a t e ( 3 ) was s y n t h e s i z e d by NaBH^ r e d u c t i o n o f e t h y l 3 - [1 70 ] o x o b u t y r a t e , w h i c h was o b t a i n e d from t h e c o r r e s p o n d i n g u n l a b e l e d compound by a c i d c a t a l y z e d exchange w i t h 1 70 - e n r i c h e d w a t e r i n e t h a n o l . Compound 3 was p u r i f i e d by d i s t i l l a t i o n i n vacuo.
C O O E t I C H , I c = o I C H , COOEt I C H , I „ • C = o I C H , C O O E t NaBH^ HC — O H I C H , 3 - [1 7O l h v d r o x y g l u t a r i c a c i d ( 4 ) was o b t a i n e d by NaBIfy r e d u c t i o n of d i e t h y l [1 70 ] a c e t o n e d i c a r b o x y l a t e f o l l o w e d by a c i d i c h y d r o l y s i s . l70 - e n r i c h m e n t o f d i e t h y l a c e t o n e d i c a r b o x y l a t e was a c h i e v e d by a c i d c a t a l y z e d exchange w i t h 1 70 -e n r i c h -e d wat-er i n -e t h a n o l . Compound 4 was p u r i f i -e d by c r y s t a l l i z a t i o n .
C O O E t I CH2 H2O* c = o H+ I C H2 I C O O E t C O O E t CH 2 NaBH, COOEt I C H , C O O H I C H , C = 0 I C H , I C O O E t HC- * O H AG 50W —X 8 C H , C O O E t C H , I C O O H 4
D i m e t h y l [1 7Q ] h y d r o x y s u c c i n a t e ( 5 ) . R e a c t i o n o f 1 70 - e n r i c h e d w a t e r and b r o m o s u c c i n i c a c i d i n t h e p r e s e n c e o f Ag2° f o l l o w e d by e s t e r i f i c a t i o n w i t h diazomethane y i e l d e d 5 c o n t a m i n a t e d w i t h d i m e t h y l f u m a r a t e . P u r i f i c a t i o n was a c h i e v e d by p r e p a r a t i v e HPLC. C O O H C O O H C O O C H , 1 1 x H C - B r H , 0 * H C — O H C H , N , HC — O H C H , A3 2 ° C H , C H , I I I C O O H C O O H C O O C H3 5 [ H y d r o x y -1 70 ] c i t r i c a c i d ( 8 ) was p r e p a r e d by a c y a n o h y d r i n s y n t h e s i s s t a r t i n g from d i m e t h y l [ ^0] a c e t o n e d i c a r b o x y l a t e f o l l o w e d by m e t h a n o l y s i s o f t h e c o r r e s p o n d i n g c y a n o h y d r i n . A l k a l i n e h y d r o l y s i s and i o n - e x c h a n g e y i e l d e d 8. P u r i f i c a t i o n o f 8 was a c h i e v e d by p r e p a r a t i v e HPLC. C O O C H , I 3 C H , I 2 c = o I C O O C H , H , 0 C O O C H I C H , c = o C O O C H , HCN C O O C H , C H2 NC — C — O H I C O O C H3 6 C O O C H , I 3 C H , O O C — C—*OH I C H , I 2 C O O C H , 2. A G 5 0 W - X 8 C O O H I l "2 H O O C - C — O H I C H2 C O O H [ 170 ] e t h a n o l ( 1 1 ) was s y n t h e s i z e d by t h e a c i d c a t a l y z e d h y d r o l y s i s o f 1,1-d i p r o p o x y e t h a n e y i e l 1,1-d i n g [1 70 ] a c e t a l d e h y d e , w h i c h was r e d u c e d w i t h L1A1H4 t o t h e c o r r e s p o n d i n g a l c o h o l . P r O PrO \ H C C H , / 3 LiAIH, 10
