Syntheses and reactivity of transition metal complexes of mono- and bicyclo- macrocyclic ligands

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S uperv i s o r : P r o f e s s o r A. M c A u l e y

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O p t i c a l l y - a c t i v e b i s ( ( - ) - ( R ) - 2 ~ m e t h y l ~ l , 4 , 7 - t r i a z a c y c l o n o n a n e ) c o m p l e x e s of N i ( I I ) / (III) h a v e b e e n s y n t h esized. The m o l a r o p t i c a l rotation, [M]D/ of the Ni(II) c o m p l e x is - 1 . 3 x l 03 deg. M^ m " 1, and th a t of the Ni(III) c o m p l e x + 1 . 9 x l 03 deg.M"lm -1. The Ni(II) c o m p l e x is r e l a t i v e l y s t a b l e in a c i d i c media, a n d the rate of d e c o m p o s i t i o n is f i r s t - o r d e r in [H+] w i t h k„ = (1.81 ± 0.09) x l O"'1 M ^ s -1. The k i n e t i c s of the r e d o x r e a c t i o n at the n i c k e l c e n t r e w e r e i n v e s t i g a t e d u s i n g M a r c u s C r o s s - c o r r e l a t i o n , a n d t h e s e l f - e x c h a n g e rate d e t e r m i n e d to b e (1.2 ± 0 . 5 ) x l 04 M _1s_1. The s y n t h e s i s of a m a c r o b i c y c l i c l i g a n d c o n t a i n i n g 14- a n d 9 - m e m b e r e d rings is described, w h i c h i n v o l v e s a C u ( I I ) - t e m p l a t e r e a c t i o n of b i s - p e n d a n t [ 9 ] a n e N 20 w i t h g l y o x a l to f o r m a c y c l a m ring. The i s o l a t e d c o n d e n s a t i o n p r o d u c t was an a m i d o l s p e c i e s f o r m e d fr o m a se r i e s of p r o t o n - s h i f t s of the i n i t i a l S c h i f f - b a s e i n t e r m e d i a t e . I n s u f f i c i e n t h y d r o g e n a t i o n of the a m i d o l c o m p l e x r e s u l t e d in an e n a m i n e species. The c r y s t a l s t r u c t u r e s of t e t r a - p r o t o n a t e d l i g a n d p e r c h l o r a t e salt a n d its Cu(II) complex, t o g e t h e r w i t h t h e a m i d o l and e n a m i n e r e a c t i o n i n t e r m e d i a t e s , were solved. The m e c h a n i s m s i n v o l v e d in b o t h p r o c e s s e s are d i s c u s s e d . In all t h e ^ (II) c o m p lexes, t he m e t a l ion is in a s q u a r e p y r a m i d a l g e o m e t r y w i t h t h e e t h e r o x y g e n b i n d i n g at the apical p o s i t i o n a n d t h e m e t a l ion

s i t t i n g a b o v e t h e N4 p l a n e t o w a r d s t h e a p i c a l donor.

The s p e c t r o s c o p i c a n d e l e c t r o c h e m i c a l p r o p e r t i e s of s q u a r e p y r a m i d a l Cu(II) c o m p l e x e s of b i c y c l o N 4X (X = 0, S or N) l i g a n d s w e r e i n v e s t i g a t e d . A s the a p i c a l d o n o r was c h a n g e d f r o m 0 to S a n d N, a c o r r e l a t i o n b e t w e e n t h e d - d t r a n s i t i o n band, A^, a n d t h e o x i d a t i o n p o t e n t i a l w a s observed, and r a t i o n a l i z e d in t e r m s of a - b o n d i n g s t r e n g t h . •In che ca s e of N40, a " s q u a r e - s c h e m e " i n v o l v i n g b o t h e l e c t r o c h e m i c a l and c h o m i c a l p r o c e s s e s w a s o b s e r v e d in t h e c y c l i c - v o l t a m m e t r i c r e d uction, w h e r e a s in t h e c a s e w h e r e X = S or N, the r e d u c t i o n is o f r e v e r s i b l e c h a r a c t e r .

The m a c r o b i c y c l o N 40 Ni(II) c o m p l e x w a s s y n t h esized. The c r y s t a l s t r u c t u r e s h o T jd a d i s t o r t e d o c t a h e d r a l g e o m e t r y with an a x i a l c o o r d i n a t i o n of t h e e t h e r o x y g e n a n d a p e r c h l o r a t e anion, a n d t h e Ni(II) ion b e l o w t h e N4 p l a n e t o w a r d s the c o o r d i n a t e d p e r c h l o r a t e . T h e s u b s t i t u t i o n r e a c t i o n s of the [Ni(III) (N40) (0H2) ]3+ c o m p l e x w i t h C l “ a n d SCN" in a q u e o u s m e dia w e r e i n v e s t i g a t e d . T h e r e a c t i o n ra t e is d e p e n d e n t not o n l y on [H+] , b u t al s o the n a t u r e a n d c o n c e n t r a t i o n of b o t h the e n t e r i n g l i g a n d a n d t h e s u p p o r t i n g e l e c t r o l y t e . A m e c n a n i s m i n v o l v i n g i o n - p a i r i n g e q u i l i b r i a a n d d e p r o t o n a t i o n of the c o o r d i n a t e d w a t e r is p r o p o s e d . The p r e p a r a t i o n a n d c h a r a c t e r i z a t i o n of t h e e t h y l e n e - b r i d g e d h i g h l y - c o n j u g a t e d b i n u c l e a r N i (II) complex, [Ni2(l,l'~ b i c y c l o - 3 , 6 , 1 0 , 1 3 - t e t r a a z a t e t r a d e c a - 2 , 1 3 - d i e n y l i d e n ) ] are d e s c r i b e d , a n d t h e m e c h a n i s m i n v o l v i n g r a d i c a l i n t e r m e d i a t e s

iv was p r o p o s e d a c c o u n t i n g for t h e d e h y d r o g e n a t i o n a n d d i m e r i z a t i o n p r o c e s s e s . B o t h t h e m o l e c u l a r s t r u c t u r e a n d c h e m i c a l r e a c t i v i t i e s o f the c o m p o u n d s h o w e d " q u a s i - a r o m a t i c " n ature. H y d r o l y s i s of t h i s c o m p o u n d was l i g a n d - b a s e d , w h e r e a s its o x i d a t i o n w a s m e t a l - b a s e d . The e l e c t r o c h e m i c a l r e d u c t i o n of t h e c o m p o u n d was a o n e - e l e c t r o n / t w o - s t e p p r o c e s s w i t h E1/2 of 0.19 V and - 0 . 0 3 V (vs F c+/0 in C H3C N ) , r e s p e c t i v e l y . The s e l f - e x c h a n g e r a t e of the f i r s t r e d u c t i o n was d e t e r m i n e d (using M a r c u s C r o s s - c o r r e l a t i o n ) t o b e 5 . 1 x l 06 M^s"*1, a n d that of t h e s e c o n d 180 M ^ s -1. E x a m iners: Dr. A. M c A u l e y (J D r ''"'G. W .-'-■fillsEnell ^ D r . P . W a n D&. J.B. T a t u m Dr. C h o w

T a b l e o f C o n t e n t s Page A B S T R A C T ii T A B L E OF C O N T E N T S v L I S T OF T A B L E S iv L I S T OF F I G U R E S xi L I S T OF S C H E M E S xiii L I S T OF A B B R E V I A T I O N S xiv A C K N O W L E D G E M E N T S xvi D E D I C A T I O N xvii C H A P T E R 1. I N T R O D U C T I O N 1 1 . 1 M a c r o c y c l i c C o m p l e x e s 2 1.1 . 1 B a c k g r o u n d 2 1.1 . 2 S y n t h e s e s of M a c r o c y c l e s 4 1.1.3 M a c r o c y c l i c E f f e c t 9 1.1.4 O t h e r E f f e c t s I n v o l v e d in M a c r o c y c l i c C o m p l e x e s 14 1 . 2 K i n e t i c a n d M e c h a n i s t i c A s p e c t s of I n o r g a n i c R e a c t i o n s I n v o l v i n g T r a n s i t i o n M e t a l C o m p l e x e s 23 1.2 . 1 S u b s t i t u t i o n R e a c t i o n s 23 1.2 . 2 R e d o x R e a c t i o n s 28 1 .2.3 A p p l i c a t i o n of M a c r o c y c l i c C o m p l e x e s in Study of I n o r g a n i c R e a c t i o n s 32 C H A P T E R 2. E X P E R I M E N T A L M E T H O D S 35 2 . 1 S y n t h e s e s 36

2 .1 . 1 N i ( I I ) / (III) C o m p l e x e s of Bis Methyl-•Substituted

[9]a n e N3 36 2 .1 . 2 M a c r o b i c y c l o N 40 and Its C o m p l e x e s 39 2 . 1 . 3 E t h y l e n e - B r i d g e d Bi-Ni(II) C o m p l e x 47 2 . 1 . 4 C o m m o n R e a g e n t s 48 2 . 2 I n s t r u m e n t a t i o n 49 2 .2 . 1 S t o p p e d - F l o w 49 2.2.2, C y c l i c V o l t a m m e t r y 51

vi 2.2.3 E l e c t r o n Sp i n R e s o n a n c e 59 2.2.4 C r y s t a l l o g r a p h y 66 2.2.5 O t h e r I n s t r u m e n t a t i o n 67 C H A P T E R 3. S Y N T H E S I S A N D R E D O X C H E M I S T R Y OF THE N i ( I I ) / (III) C O M P L E X OF BIS M E T H Y L - S U B S T I T U T E D [9]a n e N3 70 3.1 I n t r o d u c t i o n 71 3.2 S y n t h e s i s 72 3.3 P h y s i c a l P r o p e r t i e s 77 3.3.1 S p e c t r o s c o p y 77 3.3.2 E l e c t r o c h e m i s t r y 7 9 3.3.3 O p t i c a l A c t i v i t y 80 3.4 K i n e t i c I n v e s t i g a t i o n of R e d o x R e a c t i o n s of t h e Ni (II)/ (III) C o m p e l x e s 81 3.4.1 H y d r o l y s i s of t h a Ni(II) C o m p l e x 82 3.4.2 O x i d a t i o n o f [Ni (II) (Ll) 2]2+ b y [Co(OH2)6]3+ 83 3.4.3 O x i d a t i o n o f [Ni (II) (Ll)2]2+ b y Ni (IV) O x i m e 84 3.4.4 R e d u c t i o n o f [Ni (III) (Ll)2]3+ w i t h [Co (phen)3]2+ 85 3. 4.5 O x i d a t i o n of I o d i d e b y [Ni (III) (Ll) 2]3+ 85 3 . 4.6 R e a c t i o n of [Ni (II) (Ll) 2)2+ w i t h

[Ni(III) ([9] a n e N 3) 2]3+ 87

3.4.7 R e a c t i o n of [Ni (II) (Ll) 2]2+ w i t h [Ni (III) c y c l a m ) 3+ 91

3.4.8 D i s c u s s i o n 91 C H A P T E R 4. S Y N T H E S E S A N D C H A R A C T E R I Z A T I O N OF N O V E L M A C R O B I C Y C L O N4O Cu(II) C O M P L E X A N D R E A C T I O N I N T E R M E D I A T E S 96 4.1 I n t r o d u c t i o n 97 4.2 S y n t h e s i s 98 4.3 M o l e c u l a r S t r u c t u r e s 105 4.3.1 C r y s t a l l o g r a p h y 105 4.3.2 R e s u l t s 109 4.4 D i s c u s s i o n 125 4.4.1 M e c h a n i s m 125

4 .4.2 I n t e r m e d i a t e s 131 C H A P T E R 5. S P E C T R O S C O P I C A N D E L E C T R O C H E M I C A L P R O P E R T I E S OF S Q U A R E P Y R A M I D A L Cu(II) C O M P L E X E S OF b i c y c l o n 4x ( y =

o, s,

5 . 4 . 3 [Cu (II) (N4S ) ] 2+ and [Cu (II) (N5)]2+ 161

5 . 4 . 4 [Cu (II) c y c l a m ] 2+ 162 5 . 4 . 5 E f f e c t o f A x i a l D o n o r 164 5 . 4 , 6 E f f e c t o f T e t r a g o n a l P l a n e F i e l d 168 5 . 4 . 7 C o r r e l a t i o n w i t h E S R and V i s i b l e S p e ctra 169 5.5 C o n c l u s i o n s 172 C H A P T E R 6. C H A R A C T E R I Z A T I O N AND R E A C T I V I T Y OF Ni (II) A N D Ni(III) B I C Y C L 0 N 4O C O M P L E X E S 174 6 . 1 I n c r o d u c t i o n 175 6 . 2 M o l e c u l a r S t r u c t u r e 177 6.3 E S R S p e c t r a 184 6.4 E l e c t r o c h e m i s t r y 187 6.5 K i n e t i c I n v e s t i g a t i o n s 190 6 .5.1 S u b s t i t u t i o n R e a c t i o n s 190 6 . 5.2 R e d o x R e a c t i o n s 213 C H A P T E R 7. SYN T H E S I S , C H A R A C T E R I Z A T I O N A N D R E A C T I V I T Y OF A N E T H Y L E N E - B R I D G E D B I N U C L E A R_j N i ( I I) 2 C O M P L E X 217 7.1 I n t r o d u c t i o n 218 7.2 F o r m a t i o n of [Ni2(L4) ) 4+ 223 7.3 M o l e c u l a r S t r u c t u r e 231

viii 7.4 U V / V i s i b l e S p e c t r a a n d S o l u t i o n C h e m i s t r y 247 7 .4.1 U V / V i s i b l e S p e c t r a 247 7 . 4.2 H y d r o l y s i s of [Ni2(L4)]4+ in A q u e o u s S o l u t i o n 24 9 7.5 E l e c t r o c h e m i s t r y 253 7.5.1 O x i d a t i o n 254 7.5.2 R e d u c t i o n 256 7 . 5.3 p H - D e p e n d e n c e S t u d y 260 7.6 C h e m i c a l R e d o x R e a c t i o n s 264 7.6.1 O x i d a t i o n 264 7.6.2 R e d u c t i o n 266 7.6.3 K i n e t i c S t u d i e s 268 7.7 D i s c u s s i o n 273 7.7 F u t u r e W o r k 280 R E F E R E N C E S 282

LIST OP TABLES

4.1 C r y s t a l l o g r a p h i c Da t a for the Cu(II) C o m p l e x e s an d t h e H y d r o p e r c h l o r a t e Salt of the F r e e L i g a n d ---- 107

4.2 C o o r d i n a t e s Tablf; for [H4 (N40) ]4 + --- 111

4.3 I n t e r a t o m i c D i s t a n c e s f o r [H4(N40 ) ] ‘u --- 113

4.4 B o n d A n g l e s for [H4(N40 ) ] 4 + --- 113

4.5 C o o r d i n a t e s T a b l e for [Cu(II) (L2)]2 + --- 116

4.6 B o n d A n g l e s for [Cu (II) (L2)]z + --- 117

4.7 I n t e r a t o m i c D i s t a n c e s for [Cu(II) (L2)]2 + ---118

4.8 C o o r d i n a t e s T a b l e for [Cu(il) (L3)]2 + --- 122

4.9 B o n d A n g l e s for [Cu (II) (L3)]2 + --- 123

4.10 I n t e r a t o m i c D i s t a n c e s f o r [Cu(II) (,L3)]2 + ---124 4.11 C o o r d i n a t e s T a b l e for [Cu(II) (N40 ) ] 2 + --- 126 4.12 B o n d A n g l e s for [Cu(II) (N40 ) ] 2 + ---- ---— ~ 127 4.13 I n t e r a t o m i c D i s t a n c e s f o r [Cu(II) (N40 ) ] I + --- 128 5.1 R e s u l t s f r o m U V / V i s i b l e S p e c t r a of [Cu(II) (L)]2 + ---140 5.3 R e s u l t s f r o m E S R S p e c t r a of [Cu(II) (L))2+ --- 145 5.3 R e s u l t s f r o m C y c l : c V o l t a m m e t r y --- 165 6.1 C r y s t a l l o g r a p h i c Data 178

X

6.2 C o o r d i n a t e s T a b l e for [Ni(II) (N40) (C104)]+ ---180

6.3 B o n d L e n g t h s a n d A n g l e s for [Ni (II') (N40 (CIO*) ]+ --- 182

6.4 E in for [Ni3+ m (N<X) ] C o u p l e s (X = 0, S, N) in N i t r a t e a n d C h l o r i d e M e d i a --- 188 6.5 Ra t e of D e c o m p o s i t i o n of [Ni(III) (N40 ) ] 3+ in A c i d i c M e d i a --- — 191 6 . 6 K i n e t i c D a t a f r o m S u b s t i t u t i o n R e a c t i o n s --- 193 6.7 R a t e C o n s t a n t s f r o m D i f f e r e n t S u p p o r t i n g A n i o n s --- 202 6 . 8 Ra t e C o n s t a n t s f r o m D i f f e r e n t l o n i c - S t r e n g t h s --- 203 6.9 R a t e of O x i d a t i o n of SCN" w i t h [Ni(III) (N40 ) ] 3 + ---205 6.10 K i n e t i c D a t a f r o m R e d o x R e a c t i o n of [Ni (III) (N4X) ]3+ (X = O, S, N) --- 214 6.11 S e l f - E x c h a n g e R a t e s (kn ) for [Ni3V2+ (N4X) ] --- 215 7.1 C r y s t a l l o g r a p h i c D a t a for [Ni2(L4)]4 + --- 232

7.2 I n t e r a t o m i c D i s t a n c e s for [Ni2(L4))u --- 234

7.3 B o n d A n g l e s for [Ni2(L4)]4 + --- 234 7.4 A t o m i c C o o r d i n a t e s T a b l e for [Ni2(L4)]4 + --- 235 7.5 B o n d L e n g t h s of t h e " S i x - M e m b e r e d R i n g s " --- 240 7.6 The d - d B a n d s f r o m D i f f e r e n t S u p p o r t i n g A n i o n s ---- 248 7.7 R e s u l t s f r o m C y c l i c V o l t a m m e t r y --- 257 7.8 K i n e t i c D a t a f r o m R e d o x R e a c t i o n s of [Ni2(L4)]4+ a n d [Ni2(L4)]3 + --- 270

LIST OF FIGURES

3.3 K i n e t i c s D a t a for "Redox E q u i l i b r i u m R e a c t i o n s " --- 90 3.4 P l o t s of M a r c u s C r o s s - R e l a t i o n . --- 92 4.1 C r y s t a l S t r u c t u r e of [H4(N40 ) ] 4 + --- 110 4.2 C r y s t a l S t r u c t u r e s of [Cu (II) (L2) ]2+ a n d its D e p r o t o n a t e d D i m e r --- 115 4.3 C r y s t a l S t r u c t u r e of [Cu(II) (L3)]2* --- 121 4.4 C r y s t a l S t r u c t u r e of (Cu(II) (N40 ) ] 2 + -- 125 5.1 V i s i b l e S p e c t r a of [Cu (II) (N„0) ]2+ a n d [Cu (II) (L2) ]2+---- 140

5.2 E S R S p e c t r a of [Cu (II) (N40) ]2+ a n d [Cu (XI) (L2) ]2 f 144 5.3 C V of C u2+/3+ (N40) in C H 3C N ( Anodically S c a n n i n g ) 147 5.4 C V o f C u3+/2+ (N40) in C H 3CN ( C a t h o d i c a l l y S c a n n i n g ) 148 5.5. C V of C u2+/+(N40) in C H 3C N ( C a t h o d i c a l l y s c a n n i n g ) 14 9 5.6 C V of C u +/2+ (N40) in C H 3C N at -20 °C ( A n o d i c a l l y S c a n n i n g ) --- 150 5.7 C V of C u +/2+ (N40) in C H 3C N (the R e v e r s i b l e C o u p l e for t h e u n s o l v a t e d complex) --- 152 5.8 C V of C u2+/+(N4S) in C H 3C N --- 153 5.9 C V of C u2+/3+ (L2) in C H 3C N (Anodically S c a n n i n g ) --- 156

xii 5.10 C V o f C u 3+/2+ (L2) in C H 3C N (Catho d i c a l l y S c a n n i n g ) 158 5.11 C V of C u 2+/+ (L2) in C H 3C N --- 159 5.12 C V o f C u 2+/+(NS) in C H 3C N --- 162 5.13 C V o f C u 2f/3+c y c l a m in C H 3C N ---163 6.1 C r y s t a l S t r u c t u r e of [Ni(II) (N40) (C104)] + --- 178 6.2 E S R S p e c t r a of Ni(III) (N40) in A q u e o u s S o l u t i o n s of V a r i o u s S u p p o r t i n g A n i o n s --- 185 6.3 E S R S p e c t r u m of [Ni (III) ([9] a n e N 3) 2]3+ in A q u e o u s S o l u t i o n of F “ --- 186 6.4 C o r r e l a t i o n P l o t s of C a l c u l a t e d a n d O b s e r v e d kobs V a l u e s for S u b s t i t u t i o n R e a c t i o n of [Ni (N40) O H 2) ]3+ wit/ Cl" in D i f f e r e n t S u r p o r t i n g A n i o n s --- 198 6.5 C o r r e l a t i o n P l o t s of C a l c u l a t e d a n d O b s e r v e d kobs V a l u e s for S u b s t i t u t i o n R e a c t i o n of [Ni (N40) (OH2) ] 3+ w i t h Cl" in M i x e d S o l u t i o n (Triflate a n d C 1 0 4" ) --- 200

6 . 6 C o r r e l a t i o n P l o t s of C a l c u l a t e d a n d O b s e r v e d k obs V a l u e s for S u b s t i t u t i o n R e a c t i o n s of [Ni (N40) (OH2) ] 3+ w i t h Cl" in D i f f e r e n t I o n i c - S t r e n g t h (C104~ ) --- 201

6.7 C o r r e l a t i o n P l o t s of k oba(Calc.) a n d k obs(Exp.) for the r e s u l t s f r o m 2.0 M H / L i C 1 04 --- 202 7.1 C r y s t a l S t r u c t u r e of [Ni2 (L4) ]4+--- 233 7.2 U V / V i s i b l e S p e c t r a of H y d r o l y s i s o f [Ni2(L4)]4 + --- 248 7.3 U V / V i s i b l e S p e c t r a of [Ni2(L4)]4+ in H2/ N a2S04 M e d i a ( p H - D e p e n d e n t ) --- 251 7.4 C V of O x i d a t i o n of [Ni2(L4)]4+ in C H 3C N --- 255 7.5 C V of R e d u c t i o n of [Ni2(L4)]4+ in C H 3C N --- 258 7.6 C V of p H ~ D e p e n d e n c e S t u d y of [Ni2(L4)]4+ in N i t r a t e M e d i a --- 261 7. 7 E S R S p e c t r a of [Ni (III) 2 (L4) ]6+ --- 265 7.8 U V / V i s i b l e S p e c t r a of C o n v e r s i o n b e t w e e n [Ni2 (L4) ]4+ a n d [Ni2(L4)]3+ in H 20 --- 267 7.9 E S R S p e c t r u m of [Ni2(L4)]3+ in C H 3C N --- 267

LIST OF SCHEME

7.1 M e c h a n i s t i c S c h e m e of F o r m a t i o n of [Ni2(L4)]4 + --- 225 7.2 F o r m a t i o n of [ N i y o H]0 --- 230 7.3 M e c h a n i s t i c S c h e m e of H y d r o l y s i s of [Ni2(L4)]4 + --- 252 7.4 R e d o x S c h e m e of [Ni2(L4)]4 + --- 258 7.5 R e a c t i o n S c h e m e o f R e d o x a n d H y d r o l y s i s of [Ni2 (L4) ]4+--- 362

xiv M e - [9] aneN, L2 L3 L4 L' L" b i c y c l o N 40 b i c y c l o N5 ( b i c y c l o N 4S [9]a n e N3 [9]a n e N 20 [16]a n e N 5 [16]a n e N 4S [16] a n e N 40 d a p t a c n en p h e n o x i m T C N E A T AT'

LIST OF ABBREVIATIONS

-[NiATH] 2 P n A 0 - 6 H t e t r a a z a c y c l o t e t r a d e c a - 4 , 7 - d i e n o (-) 1 , l ' - b i (2, 1 3 - d i m e t h y l - 3 , 6 , 9 , 1 2 - t e t r a a z a c y c l o t r i d e c a -2,1 2-dienylidene) 2 , 2 , 3 , 9 , 1 0 , 1 0 - h e x a m e t h y l - 5 , 7 - d i o x a -6- h y d r a -1, 4 ,8,1 1 t e t r a a z a c y c l o t e t r a d e c a -3 , 8 , 1 1 , 1 -3 - t e t r a e n e

xvi

A C K N O W L E D G E M E N T S

I w o u l d l i k e to t h a n k m y superv i s o r , Dr. A. McAuley, for his guidance, e n c o u r a g e m e n t a n d h e l p d u r i n g the c o u r s e of th i s work. X w o u l d also like t o t h a n k Dr. T. W h i t c o m b e , Dr. S. Subramaniam, Dr. D. G. Fortier, a n d Dr. S a v i t r i C h a n d r a s e k a r for t h e i r assist a n c e , and m a n y u s e f u l a n d i n t e r e s t i n g d i s c u s s i o n s . T h e help fr o m Ms. B. Cameron, Ms. B. Chak, and Mr. K. Coulter, is a c k n o w l e d g e d . I t h a n k all t h e staff, b o t h t e c h n i c a l and n o n t e c h n i c a l , o f the d e p a r t m e n t o f C h e m i s t r y for t h e i r a s s i s t a n c e . I e s p e c i a l l y t h a n k Mrs. K a t h y B e v e r i d g e for c o m p l e t i n g t h e X - r a y c r y s t a l s t r u c t u r e s of t h e c o m p o u n d s p r e s e n t e d in t h i s thesis, a n d Dr. T. W h i t c o m b e for h i s h e l p w i t h p a r t of th e k i n e t i c s t u d i e s in the t h e s i s work. La s t but n o t least, I w o u l d p a r t i c u l a r l y l i k e to t h a n k my wife, Yongxin, for h e r p a t i e n c e a n d a s s i s t a n c e d u r i n g the c o u r s e of this work.

To my wife and my p a r e n t s

1.1 M a c r o c y c l i c C o m p l e x e s 1.1.1 B a c k g r o u n d

A m a c r o c y c l i c ligand, a c c o r d i n g to the d e f i n i t i o n p r o v i d e d b y Melson, is "a c y c l i c c o m p o u n d w i t h ni n e or more m e m b e r s ( i n cluding all h e t e r o atoms) a n d w i t h t h r e e or m o r e d o n o r (ligating) a t o m s" . 1 The d i s c o v e r y and s tudy of c o o r d i n a t i o n c o m p o u n d s c o n t a i n i n g m a c r o c y c l i c liga n d s date b a c k as e a r l y as the b e g i n n i n g of this century; however, the e a r l y w o r k in t h i s f i e l d was l i m i t e d to c o m p l e x e s of n a t u r a l l y o c c u r r i n g l i g a n d s su c h as p o r p h y r i n s , c o r r i n s and p h t h a l o c y a n i n e s due to t h e i r r e l a t i o n to b i o l o g i c a l l y i m p o r t a n t s p e c i e s (e.g. hemes, c y t o c hromes, and chlorophyll) or t h e i r p o t e n t i a l as d y e s t u f f s a n d p i g m e n t s.2-5 B e f o r e 1960, t h e r e w e r e o n l y a f e w s c a t t e r e d r e p o r t s of "sy n t h e t i c m a c r o c y c l e s " , m o s t of w h i c h were o f ten i n c i d e n t a l to the r e s e a r c h r a t h e r t h a n the p r i m e m o t i v a t i o n for t h e i r c o o r d i n a t i o n c h e mistry. In t h e e a r l y 1960's, s e v e r a l g r o u p s, 6-10 w o r k i n g i n d e p e n d e n t l y , s y n t h e s i z e d a v a r i e t y of c o o r d i n a t i o n c o m p o u n d s c o n t a i n i n g s y n t h e t i c m a c r o c y c l i c ligands. C u r t i s6 d e s c r i b e d t h e r e a c t i o n b e t w e e n t r a n s - b i s e t h y l e n e d i a m i n e n i c k e l ( I I ) p e r c h l o r a t e a n d acetone, a n d l a t e r, 7 a s s i g n e d to t h e p r o d u c t t h e m a c r o c y c l i c s t r u c t u r e s h o w n in S c h e m e 1.1. F o l l o w i n g t h e s e reports, t h e g e n e r a l i t y of the a b o v e t y p e of r e a c t i o n was d e m o n s t r a t e d , a n d a n e w s e r i e s of s y n t h e t i c m a c r o c y c l e s was d e v e l o p e d.11 S i nce then, a v e r y l arge n u m b e r of o t h e r s y n t h e t i c

3 m a c r o c y c l e s ha v e b e e n p r e p a r e d a n d this has led to a great i n c r e a s e in i n t e r e s t in all a s p e c t s of t h e chemisu.„y of such systems,

S i m u l t a n e o u s l y , t h e r e h a s b e e n e n h a n c e d i n t e r e s t in the ro l e of m e t a l ions in b i o l o g i c a l systems, and, as a result, " b i o i n o r g a n i c c h e m i s t r y " h a s e m e r g e d as a n e w b r a n c h of c h e m i s t r y, 12 in w h i c h c o m p l e x e s of b o t h n a t u r a l a n d s y n t h e t i c m a c r o c y c l e s are invol v e d . Thus, t h e r e has b e e n an e l e m e n t of c r o s s - f e r t i l i z a t i o n b e t w e e n t h e s e t w o d e v e l o p i n g areas. As a c o n s e q u e n c e of t h i s c l o s e r e l a t i o n s h i p , a c o n s i d e r a b l e amount of t h e r e s e a r c h i n v o l v i n g s y n t h e t i c m a c r o c y c l e s has b e e n d i r e c t e d t o w a r d s the p r e p a r a t i o n of m o d e l c o m p o u n d s for n a t u r a l m a c r o c y c l e s . A l t h o u g h t h e s e e f f o r t s h a v e not always me t w i t h s p e c t a c u l a r success, the r e s u l t i n g d e v e l o p m e n t of new, m a c r o c y c l i c l i g a n d c h e m i s t r y h a s p r o v i d e d a v a l u a b l e b a c k g r o u n d a g a i n s t w h i c h t h e n a t u r a l s y s t e m s c a n o f t e n b e seen in c l e a r p e r s p e c t i v e .

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

[Ni(cn)3](C104)a + (CHa)aCO (CIOOj

c o o r d i n a t i o n che m i s t r y , w i t h w h i c h is a s s o c i a t e d a n u m b e r of n e w t e r m s s u c h as " m a c r o c y c l i c e f f e c t" , 13 " t e m p l a t e e f f e c t" , 0 "effects on c o o r d i n a t e d m e t a l a n d l i g a n d" , 1 " m u l t i p l e j u x t a p o s i t i o n a l f i x e d n e s s" , 14 " c r y p t a t e e f f e c t" , 15 " c a t e n a n d e f f e c t" , 15 " t e t h e r i n g e f f e c t" 17 a n d so on. The e x t e n s i o n of t h i s f i e l d h a s I m p i n g e d on t o p i c s su c h as m e t a l - i o n catalysis, o r g a n i c syn t h e s i s , m e t a l - i o n d i s c r i m i n a t i o n , a n d a n a l y t i c a l methods, as w e l l as on a n u m b e r of indus t r i a l , m e d i c a l a n d o t h e r a p p l i c a t i o n s . 1 . 1 . 2 S y n t h e s e s of M a c r o c v c l e s S y n t h e s e s of m a c r o c y c l i c l i g a n d c o m p o u n d s c a n be a c h i e v e d in m a n y d i f f e r e n t ways. However, p r o c e d u r e s f o r c y c l i z a t i o n m a y be b r o a d l y s u b d i v i d e d into two m a j o r c a t e g o r i e s : (a) d i r e c t s y n t h e s i s a n d (b) t e m p l a t e s y n thesis. In (a), t h e c y c l i z a t i o n p r o c e e d s b y a c o n v e n t i o n a l o r g a n i c r e a c t i o n a n d d o e s not d e p e n d on t h e d i r e c t i n g i n f l u e n c e of a m e t a l ion. However, in (b), t h e g e n e r a t i o n of the c y c l i c p r o d u c t is i n f l u e n c e d b y t h e p r e s e n c e of a m e t a l ion, w h i c h ac t s as a " t e m p l a t e " for the c y c l i z a t i o n reaction.

A n o r m a l p r i o r i t y of b o t h d i r e c t a n d t e m p l a t e p r o c e d u r e s is t o m a x i m i z e y i e l d s of t h e r e q u i r e d p r o d u c t b y c h o o s i n g s t r a t e g i e s w h i c h i n h i b i t c o m p e t i n g l i n e a r p o l y m e r i z a t i o n a n d o t h e r r e a c t i o n s . U n l e s s s p e c i a l c i r c u m s t a n c e s are met, p o l y m e r i c m a t e r i a l s are o f t e n the m a j o r p r o d u c t w h e n m a c r o c y c l i c s y n t h e s e s are a t t e m p t e d .

5 D i r e c t S y n t h e s i s A t y p i c a l d i r e c t s y n t h e t i c p r o c e d u r e i n v o l v e s the r e a c t i o n of t w o r e a g e n t s (in e q u i m o l a r c o n c e n t r a t i o n s ) i n c o r p o r a t i n g t h e r e q u i r e d f r a g m e n t s for t h e t a r g e t m a c r o c y c l e s u c h th a t a 1:1 c o n d e n s a t i o n occurs. S u c h r e a c t i o n s are f r e q u e n t l y c a r r i e d out u n d e r d i l u t e c o n d i t i o n s , w h i c h t e n d to f a v o u r c y c l i z a t i o n b y e n h a n c i n g t h e p r o s p e c t o f t h e "half- c o n d e n s e d " m o i e t y r e a c t i n g w i t h i t s e l f " h e a d - t o - t a i l " r a t h e r t h a n u n d e r g o i n g an i n t e r m o l e c u l a r c o n d e n s a t i o n w i t h a n o t h e r m o l e c u l e in the r e a c t i o n solution. D e p e n d i n g on t h e n a t u r e of the reaction, t h e c o n d i t i o n r e q u i r e d can b e e i t h e r v e r y high d i l u t i o n or m o d e r a t e to l o w dilution. The h i g h d i l u t i o n p r o c e d u r e s are o f t e n n e c e s s a r y in the p r e p a r a t i o n of the p o l y e t h e r c l a s s of m a c r o c y c l e s , a n d an a p p a r a t u s for a c c u r a t e l y c o n t r o l l i n g this e x p e r i m e n t a l c o n d i t i o n d u r i n g such s y n t h e s i s has b e e n d e v e l o p e d.18 A r a n g e o f d i r e c t s y n t h e s i s has b e e n p e r f o r m e d u nder c o n d i t i o n s , of m o d e r a t e to low d i l u t i o n b u t s t i l l l e d to i s o l a t i o n of t h e r e q u i r e d c y c l i c p r o d u c t in r e a s o n a b l e t o high yield. Th i s t y p e o f c y c l i z a t i o n is o f t e n a p p l i e d in p r e p a r a t i o n of p o l y a z a m a c r o c y c l e s . The most, commorl.y u s e d m e t h o d u n d e r t h i s c a t e g o r y is t h e R i c h m a n a n d A t k i n s r e a c t i o n. 19 In t h i s reaction, as i l l u s t r a t e d in S c h e m e 1.2, the c y c l i z a t i o n is a c h i e v e d b y r e a c t i n g t w o p r e - t o s y l a t e d (tosyl “ p - t o l u e n e s u l p h o n y l ; Ts) r e a ctants, a n d t h e d e s i r e d

+ h Ts Olmethylformamidc

rJ

\

Ts

S c h e m e 1.2

a c i d i f i c a t i o n or r e d o x methods. R e a s o n a b l e yields (often c o n s i d e r a b l y b e t t e r th a n 50%) of t o s y l a t e d m a c r o c y c l e s may be a c h i e v e d in s pite of the fact t h a t s u c h r e a c t i o n s are u s u a l l y p e r f o r m e d at m o d e r a t e dilution. T h e s e g o o d y i e l d s are b e l i e v e d to stem, in part, f r o m the i n f l u e n c e of the b u l k y tosyl groups. T h e s e g r o u p s w i l l r e d u c e the n u m b e r of c o n f o r m a t i o n a l d e g r e e s o f f r e e d o m (such as b o n d rotation) in the r e a c t a n t s a n d / o r i n t e r m e d i a t e s . It is th i s r e d u c t i o n w h i c h is t h o u g h t to f a c i l i t a t e c y c l i z a t i o n r e l a t i v e to p o l y m e r i z a t i o n for these systems/ in essence, the e n h a n c e m e n t of c y c l i z a t i o n can be c o n s i d e r e d to b e l a r g e l y a c o n s e q u e n c e of f a v o u r a b l e e n t r o p i c e f f e c t s .

M a t a l - I o n T e m p l a t e S y n t h e s e s

S u c c e s s in s y n t h e s i s of m a c r o c y c l e s by u s i n g a m e t a l - i o n to d i r e c t t h e o r g a n i c r e a c t i o n s is l a r g e l y d u e to the t e m p l a t e effect. T h i s t e r m was f irst i n t r o d u c e d b y B u s c h to account for, t h e c o n t r o l l i n g i n f l u e n c e of the m e t a l - i o n in a p a r t i c u l a r s y n t h e s i s.8 F u r t h e r s t u d y of t h i s e f f e c t h a s s h o w n that the t e m p l a t e e f f e c t m a y be f u r t h e r d i v i d e d a k i n e t i c a n d a t h e r m o d y n a m i c effect. In the k i n e t i c t e m p l a t e effect, it is t h e d i r e c t i n g i n f l u e n c e of t h e m e t a l - i o n w h i c h c o n t r o l s the

7 s t e r i c c o u r s e of c o n d e n s a t i o n s u c h t h a t f o r m a t i o n of the r e q u i r e d c y c l i c p r o d u c t is f a c i l itated. In the t h e r m o d y n a m i c t e m p l a t e effect, the m e t a l - i o n p e r t u r b s an e x i s t i n g e q u i l i b r i u m in an o r g a n i c s y s t e m a n d the r e q u i r e d p r o d u c t is formed. E x a m p l e s f o r b o t h t y pes of the e f f e c t s h a v e b e e n d o c u m e n t e d.20 However, w hile t h e s e e f f e c t s a r e u s e f u l concepts, v e r y o f t e n t h e ro l e of the m e t a l - i o n i n a g i v e n i n si t u r e a c t i o n may b e q u i t e c o m p l i c a t e d a n d i n v o l v e b o t h effects.

An e s s e n t i a l f e a t u r e of t e m p l a t e r e a c t i o n s is the f o r m a t i o n of a new c h e l a t e ring. Th i s can b e a c h i e v e d t h r o u g h r e a c t i o n on e i t h e r t h e c o o r d i n a t e d d o n o r s o r the u n c o o r d i n a t e d a t o m s i n f l u e n c e d b y the donor. So m e of the t y p i c a l ring- c l o s i n g r e a c t i o n s are l i s t e d in T a ble 1.1. It is w o r t h m e n t i o n i n g t h a t m o s t of the r e a c t i o n s l i s t e d in T a b l e 1.1 are q u i t e s e n s i t i v e to the c h o s e n r e a c t i o n c o n d i t i o n s a n d are i n f l u e n c e d b y s u c h f a c t o r s as: the n a t u r e of t h e solvent, the pH, the o r d e r of a d d i t i o n of reagents, t h e t e m p e r a t u r e , the t i m e of t h e r e a c t i o n a n d / o r the n e e d (or o t h e r w i s e ) to p r o t e c t th e s y s t e m f r o m t h e atmos p h e r e . In a d d i t i o n , p a r t i c u l a r r e a c t i o n s wi l l be q u i t e d e p e n d e n t on the n a t u r e of t h e m e t a l c h o s e n f o r t h e t e m p l a t e reaction.

A m a c r o c y c l i c r i n g o b t a i n e d b y a t e m p l a t e r e a c t i o n o ften r e q u i r e s m o d i f i c a t i o n b y f u r t h e r rea c t i o n s . This lig a n d r e a c t i o n s t e p m a y b e p e r f o r m e d e i t h e r w i t h t h e t e m p l a t e m e t a l ­ ion s t ill i n t a c t or a f t e r r e m o v a l o f the m e t a l - i o n f r o m the ring, d e p e n d i n g on t h e n a t u r e of t h e ligand. F o r instance, in

m a c r o c y c l e s are u n s t a b l e a n d may u n d e r g o h y d r o l y t i c d e c o m p o s i t i o n in acidc or b a s i c a q u eous media. In this case., the h y d r o g e n a t i o n of t h e c o o r d i n a t e d imine f u n c t i o n s is often r e q u i r e d t o s t a b i l i z e t h e m a c r o c y c l e b e f o r e t h e m e t a l - i o n is d i s c h a r g e d . T a b l e 1.1 T y p i c a l R i n g - c l o s i n g R e a c t i o n s R E A G E N T S 'sM'KH2 + ° /, P R O O U C T S 3 = ^ ' —' XH-j R E A G E N T S t-NHz + <Aci•<3 PROOUCTS -\ /H3 J m z 0 CH3 + 2 X "

\ ?

To o b t a i n a free ligand, the c o o r d i n a t e d m e t a l - i o n in the m a c r o c y c l i c c o m p l e x f r o m the t e m p l a t e r e a c t i o n c a n be r e m o v e d u s i n g one of f o l l o w i n g proce d u r e s : a) A d d i t i o n of ex c e s s a c i d to an a m i n e - c o n t a i n i n g m a c r o c y c l e to p r o t o n a t e the a m i n e f u n c t i o n a l g r o u p s as t h e y d i s s o c i a t e f r o m t h e m e t a l ion and t h u s "sc a v e n g e " the m a c r o c y c l i c l i g a n d as a N - p r o t o n a t e d form; b) A d d i t i o n of a s t r o n g l y c o m p e t i n g l i g a n d t o a s o l u t i o n of t h e m a c r o c y c l i c c o m p l e x (such as CN“ to r e m o v e N i 2+ or S2_ t o r e m o v e C u z+) ; c) D e l i b e r a t e l y u s i n g a w e a k t e m p l a t e ion so it c a n be r e m o v e d e a s i l y l a t e r b y d i s s o l u t i o n of the c o m p l e x in a c o o r d i n a t i o n s o l vent in w h i c h t h e fr e e m a c r o c y c l i c l i g a n d has p o o r solub i l i t y / d) R e d u c i n g the m e t a l ion so t h a t t h e m e t a l - l i g a n d b o n d is w e a k e n e d (in s o m e cases, r e d u c t i o n of t h e m e t a l - i o n to a l o w o x i d a t i o n s t ate [for instance, to t h e M(0) state] leads to its s p o n t a n e o u s d i s s o c i a t i o n f r o m m a c r o c y c l e s ) .

1 . 1.3 M a c r o c y c l i c E f f e c t

The t e r m " m a c r o c y c l i c e f f e c t " was first i n t r o d u c e d by C a b b i n u s a n d M a r g e r u m13 in 1969 to a c c o u n t f o r the great t h e r m o d y n a m i c s t a b i l i t y of c o m p l e x e s c o n t a i n i n g m a c r o c y c l i c l i g a n d s as c o m p a r e d w i t h t h o s e of n o n - m a c r o c y c l i c l i g a n d s but s i m i l a r s t r u c t u r e . A n e x a m p l e of t h i s is s h o w n in T a b l e 1 . 2.21 A l t h o u g h it is e x p e c t e d t h a t the s t a b i l i t y of a p a r t i c u l a r

c o m p l e x t y p e i n c r e a s e s as t h e n u m b e r of c h e l a t e rings i n c r e a s e s (the c h e l a t e e f f e c t ) , the a d d i t i o n a l s t a b i l i t y of the m a c r o c y c l i c c o p p e r c o m p l e x was a b out an o r d e r of m a g n i t u d e g r e a t e r t h a n e x p e c t e d so l e l y fr o m the p r e s e n c e of an a d d i t i o n a l c h e l a t e ring. The o r i g i n s of th i s m a c r o c y c l i c e f f e c t h a v e b e e n i n v e s t i g a t e d on two fronts: t h e r m o d y n a m i c an d k i n e t i c . T a b l e 1.2 T h e r m o d y n a m i c s of F o r m a t i o n of C o m p l e x e s of C u 2f w i t h T e t r a a m i n e L i g a n d s in W a t e r21 A //

Tbs

Ligand log AT (kcal mol-1) (kcal m ol*‘)

( r

\)

k

/“A

1 1 t h e p a r t i c u l a r s y s t e m s the a d d i t i o n a l s t a b i l i t y was a s s i g n e d Table 1.3 P a r a m e t e r s I l l u s t r a t i n g t h e M a c r o c y c l i c E f f e c t s for t h e H i a h - s o i n Ni(II) C o m p l e x e s of T e t r a a z a M a c r o c v c l e s22 H / ^ H H / / ^ H "N NO D N N i1 1'oc^'nw

»/

r

>

j

~

\

C

n

n

U H

[NiL,*]2* + L mJC2+ s± [NiLmic]2+ + L,'OC

where oc = open chain; mac = macrocylic.

- A C A H TAS

kJ mol-1 kJ mol-1 kJ mol-1

L '/L 2 2.43 5.1 7.4

L3/L4 21.05 5.3 26.4

L5/L6 15.69 3.5 19.2

e i t h e r w h o l l y to e n t r o p y f a c t o r s or to e n t h a l p y factors Later, it w a s c l e a r t h a t t h e s e c o n t r a d i c t o r y r e s u l t s were m o s t l y d u e to t h e l a r g e u n c e r t a i n t y of t h e m e a s u r e m e n t s (Ah w a s d e r i v e d f r o m the t e m p e r a t u r e d e p e n d e n c e of the r e s p e c t i v e s t a b i l i t y c o n s t a n t s ) , a n d we r e r e s o l v e d b y s u b s e q u e n t c a l o r i m e t r i c d e t e r m i n a t i o n s . T a b l e 1.3 s u m m a r i z e s the t h e r m o d y n a m i c p a r a m e t e r s r e l a t e d to the m a c r o c y c l i c e f f e c t for t h e h i g h - s p i n Ni{II) c o m p l e x e s of four t e t r a a z a m a c r o c y c l i c l i g a n d s a n d t h e i r o p e n - c h a i n a n a l o g u e s (the o p e n - c h a i n d e r i v a t i v e w h i c h y i e l d s the mo s t stable n i c k e l c o m p l e x was u s e d in e a c h c a s e ) . Clearly, the e n t h a l p y and e n t r o p y terms m a k e s u b s t a n t i a l l y d i f f e r e n t c o n t r i b u t i o n s to c o m p l e x s t a b i l i t y a l o n g the series. D e p e n d i n g on t h e s y s t e m concerned, b o t h e n t h a l p y and e n t r o p y can p l a y a d o m i n a n t role in c o n t r i b u t i n g t o the effect.

K i n e t i c C o n s i d e r a t i o n

It is w i d e l y a c c e p t e d that t h e k i n e t i c o r i g i n of the m a c r o c y c l i c e f f e c t c a n b e a t t r i b u t e d to " m u l t i p l e j u x t a p o s i t i o n a l f i x e d n e s s " , a t e r m w h i c h was i n t r o d u c e d by B u s c h a n d c o - w o r k e r s.14 In this view, the c y c l i c l i g a n d has no "tail" f r o m w h i c h p r e p a r a t i o n and d e c o m p l e x a t i o n can begin, in c o n t r a s t to l i n e a r p o l y d e n t a t e a m i n e s w h e r e p r o t o n a t i o n is l i n k e d t o p r o g r e s s i v e r e m o v a l o f the m e t a l ion. As a c o n s e q u e n c e , e x t r e m e l y s l o w d e c o m p l e x a t i o n r a t e s are f r e q u e n t l y o b s e r v e d in t h e m a c r o c y c l i c c o m p l e x e s . In c o m p a r i s o n w i t h the o p e n - c h a i n analogues, a l t h o u g h t h e rates

1 3 o f c o m p l e x a t i o n m a y s o m e t i m e s b e s l o w e r in the ca s e of m a c r o c y c l i c complexes, t h e i r d e c o m p l e x a t i o n r a t e s a r e n o r m a l l y d e c r e a s e d to an e v e n g r e a t e r extent, a n d it is t h e l a t t e r w h i c h is r e f l e c t e d in the e n h a n c e d t h e r m o d y n a m i c s t a b i l i t i e s w h i c h are c h a r a c t e r i s t i c of the m a c r o c y c l i c effect.

O t h e r C o m m e n t s

In part, it is t h e p h e n o m e n o n of t h e m a c r o c y c l i c ef f e c t w h i c h s t i m u l a t e s t h e h i g h d e g r e e o f i n t e r e s t in t h e f i e l d of c h e m i s t r y of m a c r o c y c l i c c o m plexes. The e x t e n s i o n of the m a c r o c y c l i c e f f e c t has led to r e c o g n i t i o n of a n u m b e r of o t h e r e f f e c t s (such as the c r y p t a t e effect, t h e c a t e n a n d effect, a n d t h e t e t h e r i n g e f f e c t ) , w h i c h are i n v o l v e d in a vast v a r i e t y of m a c r o c y c l e s (including b i c y c l e s a n d m u l t i c y c l e s ) . The i n t r o d u c t i o n p r o v i d e d he r e is o n l y a b r i e f o u t l i n e of the t h e r m o d y n a m i c a n d k i n e t i c b a s e s f o r u n d e r s t a n d i n g the m a c r o c y c l i c effect. M o r e f u n d a m e n t a l f a c t o r s i n v o l v e d in th i s e f f e c t h a v e b e e n d i s c u s s e d b y H a n c o c k a n d M a r t e l l23 in t erms of: a) p r e o r g a n i z a t i o n of the ligand/ b) d e s o l v a t i o n of the d o n o r a t o m s in the c o n f i n e d s p a c e of t h e m a c r o c y c l i c cavity/ c) i n t r i n s i c b a s i c i t y effect/ d) d i p o l e - d i p o l e r e p u l s i o n in the c a v i t y of t h e ligand. M o r e recently, B u s c h a n d S t e p h e n s o n17 u s e d a m o r e g e n e r a l t e r m " m o l e c u l a r o r g a n i z a t i o n " w h i c h a t t r i b u t e s all t h e e f f e c t s a b o v e to five e l e m e n t a r y s t r u c t u r a l factors: t h e t o p o l o g i c a l factor, t h e m e t r i c factor, t h e shape factor, t h e r i g i d i t y factor, a n d c o m p l e m e n t a r i t y factor. However, t h e s e t o p i c s are far b e y o n d the s c o p e of this

i n t r o d u c t i o n a n d will not b e d i s c u s s e d here.

It is a l s o w o r t h n o t i n g t h a t a l t h o u g h the m a c r o c y c l i c e f f e c t is w i d e l y o b s e r v e d in m a c r o c y c l i c complexes, it does not m e a n t h a t all o f such c o m p l e x e s m a n i f e s t this effect. M a n i f e s t a t i o n o f the m a c r o c y c l i c e f f e c t d e p e n d s on a n u m b e r of factors, s u c h as the n a t u r e of t h e donors, t h e m a t c h b e t w e e n the m e t a l - i o n s i z e a n d the c a v i t y of c y c l i c ligands, the size of c h e l a t e rings, t h e r i g i d i t y of the s t r u c t u r e formed, the n a t u r e of t h e solvent, and so on. Indeed, it is not rare to o b s e r v e s o m e m a c r o c y c l i c c o m p l e x e s t h a t are less sta b l e th a n t h e i r o p e n - c h a i n c o u n t e r p a r t s.24 1.1.4 O t h e r E f f e c t s I n v o l v e d in M a c r o c y c l i c C o m p l e x e s E f f e c t o n t h e L i g a n d F i e l d I n v e s t i g a t i o n o f l i g a n d f i e l d spectra, t o g e t h e r w i t h data f r o m m a g n e t i c s u s c e p t i b i l i t i e s a n d e l e c t r o n spin r e s o n a n c e ( e s r ) , p r o v i d e the b a s i s for t h e a s s i g n m e n t of e l e c t r o n i c c o n f i g u r a t i o n s of t r a n s i t i o n - m e t a l ions. M a c r o c y c l i c ligands o f f e r s e v e r a l i m p o r t a n t a d v a n t a g e s for s p e c t r o s c o p i c stud i e s of t r a n s i t i o n - m e t a l c o m p l e x e s . C o n s i d e r a b l e u s e has b e e n m a d e of t h e a b i l i t y of t e t r a d e n t a t e m a c r o c y c l e s to m a i n t a i n a c o n s t a n t p l a n a r s t e r e o c h e m i s t r y a b out a m e t a l ion w h i l e a d d i t i o n a l n o n c y c l i c a xial l i g a n d s are v a r i e d s y s t e m a t i c a l l y . T h e s e s t u d i e s o f the i n f l u e n c e of t e t r a g o n a l g e o m e t r i e s on the e l e c t r o n i c c o n f i g u r a t i o n s of m e t a l io n s h a v e b e e n g r e a t l y a i d e d b y m a c r o c y c l i c l i g a n d s.14'25"20 Su c h l i g a n d s n o r m a l l y

1 5 p r o d u c e s t r o n g e r l i g a n d fields th a n the c o r r e s p o n d i n g o p e n - c h a i n ligands. This i n c r e a s e in l i g a n d f i e l d b y c o o r d i n a t i o n of the m a c r o c y c l i c l i g a n d was a t t r i b u t e d in e a r l y s t u d i e s to a c o n s t r a i n i n g or c o n s t r i c t i v e effect. 26-28 M o r e recently, however, i n v e s t i g a t i o n c a r r i e d out b y H a n c o c k et a l29 has s h own t h a t the i n c r e a s e in t h e i n t r i n s i c b a s i c i t y of n i t r o g e n d o n o r s is a d o m i n a n t f a c t o r in the triazaraacrocyclic systems. It m a y be p o s s i b l e th a t b o t h o f t h e s e two f a c t o r s h a v e an e f f e c t on th e i n c r e a s e in the l i g a n d field, a n d w h i c h one of t h e m is m o r e i m p o r t a n t will d e p e n d on the s y s t e m c o n c e r n e d .

Effect on the Redox Nature of the Metal Centre

The c a p a c i t y of m a c r o c y c l i c l i g a n d s t o s t a b i l i z e u n u s u a l o x i d a t i o n st a t e s of a c o o r d i n a t e d m e t a l i o n has b e e n w e l l - d o c u m e n t e d.30 F o r example, b o t h t h e h i g h - s p i n a n d l o w - s p i n Ni(II) c o m p l e x e s of c y c l a m are o x i d i z e d m o r e r e a d i l y to Ni(III) s p e c i e s t h a n are t h e c o r r e s p o n d i n g o p e n - c h a i n c o m p l e x e s . Indeed, t h i s c a p a c i t y has b e e n w i d e l y u s e d in the s y n t h e s e s of a v a r i e t y of c o m p l e x e s w i t h m e t a l c e n t e r s e x h i b i t i n g less c o m m o n o x i d a t i o n states, w h i c h m a y not b e s t a b l e o t h e r w i s e.30

In g e neral, the e f f e c t of m a c r o c y c l e s o n the r e d o x n a t u r e of t h e m e t a l c e n t e r is r e f l e c t e d in the c h a n g e in E° of the m e t a l c o n cerned, and r e s u l t s f r o m t h e s p e c i f i c p r e f e r e n c e of t h e m a c r o c y c l e for t h e m e t a l c e n t r e at o n e o x i d a t i o n state o v e r another. Th i s m a y be b e s t e x p l a i n e d b y t h e e q u a t i o n s s h o w n in eq. (1.1). T h e c h a n g e in t h e r e d o x p o t e n t i a l of t h e

m e t a l center, AE, is d i r e c t l y r e l a t e d to the r a tio of the c o m p l e x a t i o n c o n s t a n t s of the m a c r o c y c l i c l i g a n d w i t h the

M L maon+ -> M L ma0(n+1,+ + e“ (E°(mac))

^l(mao)) I I (^2 (mao))

M n+ + Lmac -> M (n+1)+ + Lroao + e"

B°(Me) = E°(m) - ( R T / n F ) l o g ( K2(mac)/ K 1(mac)) (1.1) or

A E = E°(mac) - E°(m)

= - (RT/nF) log (K2<mae)/ K 1(mac)) (1.2)

m e t a l ion at d i f f e r e n t o x i d a t i o n states, K2(mac)/K 1(mao). Wh e n the m a c r o c y c l i c l i g a n d has a h i g h e r c o m p l e x a t i o n constant, K 2(mac), w i t h a m e t a l at a h i g h e r o x i d a t i o n state, [ (n+1) +], than that, (mac)t at a l o w e r o x i d a t i o n state, [n+], the r e d o x p o t e n t i a l on t h e m e t a l c e n t r e for the [ (n+1)+ ] / [n+] c o u p l e will be r educed, a n d t h u s t h e m e t a l c e n t e r at the o x i d a t i o n state of [(n+l)+] is s t a b i l i z e d . This is o f t e n the case for Ni(III) p o l y a z a m a c r o c y c l i c c o m p l e x e s.30 On t h e o t h e r hand, if the

l i g a n d b o n d s m o r e s t r o n g l y w i t h t h e lower o x i d a t i o n state m e t a l ion, t h e r e d o x p o t e n t i a l will b e increased, and hence, t h e l o w e r o x i d a t i o n s t ate w i l l be s t a b i l i z e d . Th i s oc c u r s f r e q u e n t l y w i t h the Cu(I) c o m p l e x e s of p o l y t h i a or imine m a c r o c y c l i c l i g a n d s w h e r e the d o r b i t a l s on t h e S d o n o r or the a n t i - b o n d i n g n o r b i t a l of the C = N b o n d are a b l e to w i t h d r a w e l e c t r o n d e n s i t y f r o m t h e Cu(I) m e t a l c e n t e r t h r o u g h d ^ d g or d^r^imina i n t e r a c t i o n s , a n d c o n s e q u e n t l y , s t r e n g t h e n t h e M - d o n o r

17 b o n d s and i n c r e a s e the c o m p l e x a t i o n c o n s t a n t , K 1<mao). (This can also be i n t e r p r e t e d in terms of t h e d e l o c a l i z a t i o n of the e l e c t r o n d e n s i t y at the Cu(I) center).

The s t r u c t u r a l f a c t o r s i n f l u e n c i n g e l e c t r o c h e m i s t r y a r o u n d the Ni(II) c e n t e r have b e e n i n v e s t i g a t e d b y B u s c h and c o - w o r k e r s31"33 u s i n g a v a r i e t y of t e t r a a z a m a c r o c y c l i c ligands. The t y p i c a l r e s u l t s are shown in Fig. 1.1. It w a s d e m o n s t r a t e d

F i g u r e 1.1 E1/2 for the N i2V N i 3f C o u p l e in T e t r a a z a Macrocyclic, C o m p l e x e s vs. A g / A g N 03 (0.1M) R e f e r e n c e E l e c t r o d e (in V) . 33

t h a t t h e o v e r a l l r e d o x p r o p e r t i e s of a g i v e n s y s t e m are i n f l u e n c e d b y t h e m a c r o c y c l i c r i n g size, t h e c h a r g e on the ligand, t h e n a t u r e of t h e l i g a n d s u b s t i t u e n t s a n d t h e extent

a n d t y p e of l i g a n d unsatu r a t i o n , a n d the e f f e c t s of these f a c t o r s a p p e a r to be s e p a r a b l e and additive. Later, t h i s work w a s e x t e n d e d to the s y s t e m w h e r e a d i f f e r e n t ty p e of d o n o r was i n v o l v e d.34 In general, the s t r u c t u r a l f a c t o r s w h i c h favour h i g h o x i d a t i o n s t a t e s are: (i) the i n c r e a s e in the n e g a t i v e c h a r g e on the ligand, a n d (ii) the b e t t e r m a t c h b e t w e e n the s i z e of t h e Ni(III) ion and t h e c a v i t y of the c y c l i c ligand. A n i n c r e a s e in l i g a n d u n s a t u r a t i o n , and s u b s t i t u t i o n on the c h e l a t e r i ngs b o t h f a v o u r the l o w e r o x i d a t i o n states. F u r t h e r m o r e , as t h e d o n o r t y p e c h a n g e s f r o m 0, S, to N, the Ni(III) s t a t e b e c o m e s m o r e stable.

The g e n e r a l i t y of the r e s u l t s a b o v e can also be e x t e n d e d to the C u (II)/Cu (III) s y s t e m.35 However, b e c a u s e the Cu(III) i o n is s m a l l e r t h a n the Ni(III) ion, the s m a l l e r m a c r o c y c l e s

(such as [ 1 2 ] a n e N 4) are able to s t a b i l i z e Cu(III) f u r t h e r than t h e l a r g e ones (such as [14] a n e N4) , 35 w h i l e the Ni(III) ion m a t c h e s t h e b e s t w i t h [14 ] a n e N 4. In so m e cases, t h e b e t t e r o r b i t a l o v e r l a p b e t w e e n the m e t a l a n d the donors, c a u s e d b y c o n f o r m a t i o n or r i g i d i t y of t h e c y c l i c ligand, m a y also m a k e a s i g n i f i c a n t c o n t r i b u t i o n in s t a b i l i z i n g u n u s u a l o x i d a t i o n states. E f f e c t s o n C o o r d i n a t e d M a c r o c y c l i c L i g a n d s C o o r d i n a t i o n of t h e m e t a l ion to a m a c r o c y c l i c l i g a n d not o n l y has an i m p a c t on the c h e m i s t r y of t h e m e t a l centre, but a l s o i n f l u e n c e s t h e c h e m i c a l r e a c t i v i t y of the ligand. In the c o u r s e of the d e v e l o p m e n t of s y n t h e t i c r o u t e s to m a c r o c y c l i c