! " #$%&'$%(%&(%)* !"!#$ +,*',-%%,./*0%*1*'2. 3/4*'52.*6%7 8 9:70 3 987; 3 9 30%,0<=*$(5*5**=*70 3 9: 3>?% ][ 10 ][ ][ 10 ][ 1414 + − + + − − +=→= H CH H OH a (4@$57 8 9 7 8 9A 3A :BAC A ≥A 3" M H OH 8 14 10 ][ 10 ][ − + − − ≤= D.(EFG7; 3 9) ] 100 1 ][ a COH ≤ − BAC 7 8 9: →<:3$' HA 3" B,,.$*'C =*'IEFG7; 3 94% 'F<BAC7 8 9 7 8 9A 3A : %&' ()* +,*',-%.2*%,(J0%*1*'2.21$5 )5K*'J%,$5 08 ; → 0 3 8 L ; 8 ][ ][ .][ ][ ]].[[ − + −+ =→= A HA KH HA AH K aa 3/4*'52.*6%7 8 9:70 3 987; 3 9(70 3 9:7 8 97; 3 9 3-*$.EF5*?J$/*' :709870 3 9(709: 70 3 9 709: 7 8 987; 3 9 (EI%709)570 3 9)5EI%7 8 9F4=*M2/%@ )2( ][][ ][][ .][ −+ −+ + − +− = OHH OHHC KH a a %E%6** 6*'4-'1*2*' gd gdaagd H OHCKH ][ 10 ][,][ 14 + − −+ == A 4J*FM%,4J(J 7 8 9)57; 3 9214J*F) )5 NJ< NO'1***=*?=*'IEFG 7; 3 9 4% 7 8 9 **' )P* % I EF G 7 8 9 4% % agdgd COHOH 100 1 ][][ ≤≈ −− BC4F5* aa a a CKOHHH OHH C KH .]].[[][ ][][ .][ 2 =−→ − = −++ −+ + 14 10][ −+ += aa CKH agdgdgd CHOH 100 1 ][H ,][ 100 1 ][ ≤≤ ++− 2 [ ] + = a a H K C L agdgdgd CHOH 100 1 ][H ,][ 100 1 ][ >≤ ++− F'F<BC aa aa CK KK H ++−= + 42 ][ 2 + ()* P0<=*$(M2/%. 8 %F%%A)5A 8 %F%%)5A0 3 *=* 7 8 9 % :70 3 9 P 0<=*$(4A 8 %*'M %7 8 9 ][ ]].[[ 2 2 − −+ = HA AH K a (47 8 9 % :70 3 9≈ B)Q7 8 9:70 3 9C D.(7 8 9:7 8 9 %A 8 DQ 5*'4J*F) A BHA$1*C*=*%I$J(7 8 9:7 8 9 %A M%$5 N,%, 0*2*%,(J %6*<*2*%,(J ,-./'$ #$01 ()* C1*'2.%,/*$***1*'2.%,(J 8 ,%,/*<=*$(4*1$5%%J/*%,(J)5*%R 2MN*<%F%,%O$5<%F%,/* EC1*'2.%,/**F**1*'2.%,(J =*'IEFG 8 %F%,(J ),6*<,,P*/<$A 3 )5 L ;;A 3 B L ;;%< : MS!C ][ ][ .][ ][ ]][[ 3 3 3 3 − + +− =→= COOCH COOHCH KH COOHCH HCOOCH K aa 3/4*'52.*6%7 8 9:7 L ;; 3 987$ 3 987; 3 9 3%,MEFG7; 3 97$ 3 9: $ :A 3 D.(7 L ;; 3 9:7 8 9A 3 3$EF5*?J$/*'7 L ;;987 L ;; 3 9:A 3 3 F G 7 L ;; 3 9 4% 7 L ;;9 )Q %, (J * ? *=* 7 L ;;9:A 3 ()5EI%7 8 94=* 14 2 5 10][ 10 .10.78,1][ −+ − −+ − = H H (42/%< %CP*/<%,(J TFF,,%%,(J0 U )50 UU /4*'52.*6%7 8 9:70 3 U 9870 3 UU 9BVCBEFG7; 3 9)Q%,C ][ ]][[ I I HA HA HA K I +− = ()5BVC ][ ][ ][ ][ ][ ++ + += H HA K H HA KH II HA I HA III ( ][][][ 2 IIHAIHA HAKHAKH III += + J%%%,0 U )50 UU ?(JM%I$J('1*2*' 0 II 0 ][HA ,][ III HAHAI CCHA ≈≈ 002 ][ IIIIII HAHAHAHA CKCKH +=→ + BLC .* N 0 II HAHA CK %6* $5 7 8 9 '1* 2*' 5 0 U % 4 *J %O % 0 U 4*',*',-%*'/) 0 IIII HAHA CK R2M%I)J$/EI%BLC,,/*' 222 ][][][ +++ += III HHH J$.* 31*'2.%,(J*'2*'5K*'J ?%**1%I$J( '1*2*'7 8 9EK*'7 8 9%F%,/**J4*'%,(J 31*'2.%,(J?%**15K*'J *'2*'*M%I $J('1*2*'7 8 9EK*'7 8 9%F%,%*1*'2.$**J4*'%,(J 3J )5*1*'2.%,(J21*'2*'M'F<BLC 2#.* CJNJ<5%,/*)5E/* <:SM ECJNJ<5%,/*)5E(J 6*<*2*%,(J<HSM %CJNJ<5%,(J)5E/* 6*<*2*E(J<WSM ,C<,*',-%J4*'5 +,*',-%J4*'5 0<=*$(5*5*4*'*% 0→ 8 80 3 0 3 $5A2E 0 3 8 ;→0 3 8; 3 EA 0 3 8 ;→ 08; 3 E 5*' EA WW EM −− > HAA CC 2 *=*,,%IN*%O%Elà 0 3 M 0 3 0 )5%6*E/**)5*1*'2.$**0 3 *=*,,2/%%* %O%E0 3 )56*<,*',-%*%O%0 3 C<,*',-%J%**$*'6* +J0%**0 3 $5A**$*'6* 0 3 8 ;→0 3 8 L ; 8 0 0 3 8 ;→ 08; 3 E 0 0%, 0%%%K*'J%,$1*$/$5 ][ ]][[ ][ ]][[ 2 2 2 1 − −+ −+ = = HA AH K AH HAH K a a ][ ][][ 2 22 21 AH AH KK aa −+ =→ /4*'52.*6%7 8 987 8 9:7; 3 9870 3 9870 3 9BVC EF5*?J$/*'7 09870 3 9870 3 9::7 8 9 (7 8 9)5BVC7 8 987 09870 3 9870 3 9:7; 3 9870 3 9870 3 9 →7 8 987 09:7; 3 9870 3 9BC 0 3 )52*')45$5A%,4J(JB%6 8 $/)5$5.E4J(JB= /J 8 9CR2M%IEFG7 8 94%7 09)57; 3 94%70 3 9 .%BC7 09:70 3 9 ()5EI% A ( ) 2121 2 2 1 .][ aaaa pKpKpHKKH +=→= + 3./'$ ()*0145)6 )7'$ +,*',-%%%,(J0*1*'2.21 )5E$=*/<0 3 B,,/*' J0C%*1*'2.21$5 E ][ ][ ][ ][ ]][[ − + −+ =→= A HA KH HA AH K aa /4*'52.*6%7 8 987 8 9:7; 3 9870 3 9 7 8 9: E →70 3 9: E 87 8 97; 3 9 EF5*?J$/*'70 3 98709: 8 E 709: 8 E 70 3 9: 8 E 3 E 37 8 987; 3 9: 7 8 987; 3 9 ('4-70 3 9)5709)5EI%7 8 94=* ][][ ][][ ][ −+ −+ + −+ +− = OHHC OHHC KH b a a AJ,*',-%%6*%,7 8 9WW7; 3 99 ][ ][ ][ + + + + − = HC HC KH b a a J,*',-%%6*E7 8 9HH7; 3 9 ][ ][ ][ − − + − + = OHC OHC KH b a a L )5 E 5*'?$*)7 8 9)57; 3 9B('><4*'/%JC b a a b a a C C pKpH C C KH log][ +=→= + 81 !"$9 AX6*<%F,, C;A 3 )5A 3 EC$*A 3A )5A 3L %CMAB%< : MLC ,C $MAB%< L :MS!C VC ; MAB< ;3 :AM C VYC ; L MA V'CB C ; L MA C; L MA C ; MA =YM'%EJ0%,%4E*%%< A :"ML!)5< :AML! X6*<%FJ/5*5 C L MA) L ;;MAB%< L :< L;; :MS!C EC L M) ; MAB< ;3 :AM C LX6*<%FP*/<,,'1 C 0%, $%% ! ;;; M B< : LML"C )5 ?$ $%% ! ;;; M EC $M!) L MAB%< L :MS!C XR*',-%2.2/%%I*E-5!'XZ%F L ;;)!'XZ%F L ;;6* C<,,21 EC<,,?=$%*1*'2.'XZ %C<,,?=;%*1*'2.'XZ ,C<,,?=!M!Z*% . /4*'52.*6%7 8 987 8 9:7; 3 9870 3 9870 3 9BVC EF5*?J$/*'7 09870 3 9870 3 9::7 8 9 (7 8 9)5BVC7 8 987 09870 3 9870 3 9:7; 3 9870 3 9870 3 9 →7 8 987 09:7; 3 9870 3 9BC 0 3 )52*')45$5A%,4J(JB%6 8 $/)5$5.E4J(JB= /J 8 9CR2M%IEFG7 8 94%7 09)57; 3 94%70 3 9 .%BC7 09:70 3 9 ()5EI% A ( ) 2121 2 2 1 .][ aaaa pKpKpHKKH +=→= + 3./'$ ()*0145)6 )7'$ +,*',-%%%,(J0*1*'2.21 )5E$=*/<0 3 B,,/*' J0C%*1*'2.21$5 E ][ ][ ][ ][ ]][[ − + −+ =→= A HA KH HA AH K aa /4*'52.*6%7 8 987 8 9:7; 3 9870 3 9 7 8 9: E →70 3 9: E 87 8 97; 3 9 EF5*?J$/*'70 3 98709: 8 E 709: 8 E 70 3 9: 8 E 3 E 37 8 987; 3 9: 7 8 987; 3 9 ('4-70 3 9)5709)5EI%7 8 94=* ][][ ][][ ][ −+ −+ + −+ +− = OHHC OHHC KH b a a AJ,*',-%%6*%,7 8 9WW7; 3 99 ][ ][ ][ + + + + − = HC HC KH b a a J,*',-%%6*E7 8 9HH7; 3 9 ][ ][ ][ − − + − + = OHC OHC KH b a a L )5 E 5*'?$*)7 8 9)57; 3 9B('><4*'/%JC b a a b a a C C pKpH C C KH. )7'$ +,*',-%%%,(J0*1*'2.21 )5E$=*/<0 3 B,,/*' J0C%*1*'2.21$5 E ][ ][ ][ ][ ]][[ − + −+ =→= A HA KH HA AH K aa /4*'52.*6%7 8 987 8 9:7; 3 9870 3 9 7 8 9: E →70 3 9: E 87 8 97; 3 9 EF5*?J$/*'70 3 98709: 8 E 709: 8 E 70 3 9: 8 E 3 E 37 8 987; 3 9: 7 8 987; 3 9 ('4-70 3 9)5709)5EI%7 8 94=* ][][ ][][ ][ −+ −+ + −+ +− = OHHC OHHC KH b a a AJ,*',-%%6*%,7 8 9WW7; 3 99 ][ ][ ][ + + + + − = HC HC KH b a a J,*',-%%6*E7 8 9HH7; 3 9 ][ ][ ][ − − + − + = OHC OHC KH b a a L )5 E 5*'?$*)7 8 9)57; 3 9B('><4*'/%JC b a a b a a C C pKpH C C KH log][ +=→= + 81 !"$9 AX6*<%F,, C;A 3 )5A 3 EC$*A 3A )5A 3L %CMAB%< :