From algal polysaccharides to cyclodextrins to stabilize a urease inhibitor.

(1)

HAL Id: hal-01063896

https://hal.archives-ouvertes.fr/hal-01063896v2

Submitted on 14 Oct 2014

HAL is a multi-disciplinary open access archive for the deposit and dissemination of sci- entific research documents, whether they are pub- lished or not. The documents may come from

L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de

From algal polysaccharides to cyclodextrins to stabilize a urease inhibitor.

Danièle Pro, Samuel Huguet, Mustapha Arkoun, Caroline Nugier-Chauvin, Jose María García-Mina, Alain Ourry, Dominique Wolbert, Jean-Claude Yvin,

Vincent Ferrières

To cite this version:

Danièle Pro, Samuel Huguet, Mustapha Arkoun, Caroline Nugier-Chauvin, Jose María García-Mina, et al.. From algal polysaccharides to cyclodextrins to stabilize a urease inhibitor.. Carbohydrate Polymers, Elsevier, 2014, 112, pp.145-51. �10.1016/j.carbpol.2014.05.075�. �hal-01063896v2�

(2)

3 3 1

!"#$!%&'()*+,-&"!&%!./012!+!3"&$"!)'#+4#!-"5-6-,&'2!$-,5!787*&9#:,'-"!$+4!;'#;+'#9

<

15#!7&(;*#:!=>?./01!$+4!%)**8!75+'+7,#'-@#9 A

15#!4,+6-*-,8!&%!./01!+"9!,5+,!&%!=>?./01!-"!+7-9-7!(#9-+!$#'#!4,)9-#9!68!.BC D

E=FG!&%!,5#!=>?./01!7&(;*#:!$+4!9#,#'(-"#9 HI

J K

(3)

9 3 3 1

!"#$"#%$!&$$'!!(#)##!& !'!$

* +,

-./012345678^.8⁹4:.;<324=<><3?8^.8⁹4@<A?.BC.4D6E7</8^F8^G4H.6720/34I<>036JHC.<K0/8^.8⁹4L7AM4 ++

@.60.4N.6F0.J@0/.8³4D2.0/4O<66P8^F8^G4-7;0/0Q<34R72936?8^.8⁹4L3./JH2.<G34SK0/8^T4U0/F3/?4 +V

W3660163AX⁸^.8⁹ +Y

+Z

.4[F7234I.?07/.234:<BM603<634G34HC0;034G34\3//3A84HI\:84]@\4^__^84``4D22M34G34a3.<203<84 +b

H:4cdefg84fcgde4\3//3A4H3G3h4g84W6./F3 +i

94]/0K36A0?M43<67BM3//34G34a63?.>/384W6./F3 +j

F4]/0K36A0?M4G34H.3/4a.AA3JI76;./G0384]@\4kcd4[F7BCPA0727>034UM>M?.2384D>67/7;0343?4 +l

/<?60?07/A4I84H84:m4[AB2./.G34G342.4B.0h84`ndf_4H.3/84W6./F3 +*

G4oI\D84]@\4kcd4[F7BCPA0727>034UM>M?.2384D>67/7;0343?4/<?60?07/A4I84H84:m4[AB2./.G34G34 V,

2.4B.0h84`ndf_4H.3/84W6./F3 V+

34p0;.F4D>674o/?36/.?07/.2845720>7/74G34D6.q<60JO6F7P3/4H.2234H4/rf_4[Jf``^d4O6F7P3/84 VV

:B.0/ VY

T4p0;.F4D>674o/?36/.?07/.284_g4DK3/<34W6./E20/4\77A3K32?84fcnde4:.0/[email protected]./F3 VZ

Vb Vi

H7663AB7/G0/>4.<?C76s4U0/F3/?4W3660163A Vj

p32s4tuffv4_f4_f4ed4ce Vl

W.hs4tuffv4_4_f4_f4e`4kk V*

K0/F3/?mT3660363Aw3/AFJ63//3AmT6 Y,

Y+

YV

(4)

3 3 1

!"#$% #$&%"'%%("")$*$$"'!"("%

+, ++

-./012345678^.8⁹4:;<=.>?.4@6A7;/8^B8^C4D.6720/34E;F036GD?.;H0/8^.8⁹4I7<J4:.60.4K.6B0.G:0/.8³ +L

@2.0/4M;66N8^B8^C4I3./GD2.;C34OH0/8^P4Q0/B3/=4R3660163<S⁸^.8⁹ +T

+U

.4VB7234E.=07/.234W;>J603;634C34D?0X034C34Y3//3<84DEYW84Z:Y4[\\[84]]4@22J34C34^3.;203;84 +_

DW4`abcd84c`dab4Y3//3<4D3C3e4d84R6./B3 +f

94Z/0H36<0=J43;67>J3//34C34^63=.F/384R6./B3 +g

B4Z/0H36<0=J4C34D.3/4^.<<3GE76X./C0384Z:Y4h`a4VB7>?N<0727F034QJFJ=.2384@F67/7X0343=4 Li

/;=60=07/<4E84D84Wj4V<>2./.C34C342.4>.0e84]kac\4D.3/84R6./B3 Ll

C4mEY@84Z:Y4h`a4VB7>?N<0727F034QJFJ=.2384@F67/7X0343=4/;=60=07/<4E84D84Wj4V<>2./.C34C34 L,

2.4>.0e84]kac\4D.3/84R6./B3 L+

34n0X.B4@F674m/=36/.=07/.2845720F7/[email protected];60GM6B7N3/4D.2234D4/pc\4VGc]][a4M6B7N3/84 LL

W>.0/ LT

P4n0X.B4@F674m/=36/.=07/.284\d4@H3/;34R6./A20/4Y77<3H32=84c`kab4W.0/=4:.2784R6./B3 LU

L_

q(% %rsG^;=N2G>?7<>?767=60.X0C34tE^5nu40<4.4P36=020o364v0C32N4;<3C4P7640=<4;63.<34 Lf

0/?090=0/F4>67>36=03<j4E3H36=?323<<84P76X;2.=07/<4B;663/=2N4B7XX36B0.20o3C4.634B7X>23e4./C4 Lg

C74/7=4.H70C4<3H3634C3B63.<347P4.B=0H0=N4C;34=74=?3427v4<=.9020=N47P4=?34907.B=0H34B7X>7;/C4 Ti

;/C364.B0C0B4B7/C0=07/<j4@BB76C0/F4=740=<4<=6;B=;6384E5^n4v.<4=?7;F?=4=74934.9234=740/=36.B=4 Tl

v0=?497=?4>72.64.CC0=0H3<849N40=<4>?7<>?76.X0C34P;/B=07/84./C4?NC67>?790B47/3<84=?67;F?40=<4 T,

.2AN24B?.0/j4m/4=?0<4B7/=3e=84./C40/476C364=74<0X>20PN4P76X;2.=07/<47P4=?0<4907.B=0H34B7X>7;/C84 T+

.4>./3247P4/.=;6.24>72N<.BB?.60C3<4v.<4<=;C03C840/B2;C0/F4<=.6B?84wGt]xcuGF2;B./<84 TL

B.66.F?3/./<4./C4.2F0/.=3<j4y34.2<74;<3C4BNB27C3e=60/<84B?.6.B=360o3C4=?34X7<=4<=.9234 TT

(5)

3 3 1

!"#$%&' "()'*))"'"#")+"&,-./0"#(""' 12

)3)"#&'(&'()''"4 15

16

789:;<=>?-./0@A)(()3#)@B3)"@CDEFG%H)@I")(#@A&' "( 1J

2K

LMNOPQ<;=RSQT;P 2U

0#),()"#(,"!)V(",'*(4-"&""# 2W

,("#)&&"#X'+&YZ#(D[\[E+""#"'&,"+'3()')"

2]

)!'"#,("(&")X)",)X&E"#^)_.)()ED`\a+&I(

2b

CI(ED`\aGE!#!)+c"&)!)(''+&"#-+/(X,("#+()_"#(3#

21

D`da4e)"E()#)+)(")"",)&,("X(4f!*(E) 22

&Fgh,"#)*))+"(3)+(+'+&)"E(*3"#,,&,"# 25

"(3)3("(3()&(c()''3#+"()"3"(,)")'i( 26

()40#))","#)""(3,)"&('))*)"X)"E)!) 2J

'))3"'34/)")())+"))""(3)()E)'()#+"( 5K

(""#"&,"("E!##)+,),()"3(!"#C0(_E\gDgG4 5U

j)&E"#,#')+"()"#,",()"

5W

*")3("(E+",'))"')(&,)(3!#("#&)3,)"&

5]

'()"(3'"()')(Ck_(El#)('"%f)#Ef)("3m 5b

*.(E\ggn@o))E-3&E.(#)""mpE\gg[G4 51

-("'#)*'""#)(_"3,))(3),#)*3)"%() 52

)"*"q,(")#&'(cE##"()''Crs3X")4E\gg[@

55

j"")4E\gg[@0(_E\gDgGtE()+","(,)"#)q) 56

"#,)"E"#()E(( ('"E44&('E"()XE"#)')X 5J

'(*)"*E'&)')'CrArGC-mf+(ED``\@0(_E\gDgGtE+"#"(+"3 6K

(6)

3 3 1

!"!#$ "%& ''( )"*+(! +$+*$", -.

#)*$" "'%&(!" #! $ !$ "*+*'"'+$# -/

+')$0"%1(#+ $"!)*$'$2*'"$'( ""%1(" $$3"

-4

+( 3' ) ""$+( +"+" ') "*+*)(*""%5 -6

" +,++ $)")787 9+$$9 $) ' !$#,"+"

-:

""!$!(""$$+*$+! 3(((!"))+ -;

""!$#9'3(* ,+')$0"+ *" $" ' -<

#(*"%=$$#,>?!*#$?(("( '@ABC1D+ !*+( "' --

$2*')*$@ED,!* $" "$'+787,"$' *$"

-F

3(* '787%8"2*$#,++ $$# $ !$(!"" !$0) FG

" $' #"" $3H"%

F.

F/

1('$)3+*'" 'I)*$"" ) ' +(

F4

),H'( +$)($! $ +" #%

F6

J3,'+ '")*")* "(!", ')! "+" +(",(($('( F:

+$9#)*"())+$#%E)$*+ " (2* $#)"$"

F;

@J, *)( + '""!$#)'+$$'","#,!'"#$H' F<

3(**"+ ""D, !+) +"@*,3 2* $#D, '3 F-

")((!"@$$#,(#'($+I(#'(!+! $ +," !$# '!$# FF

"$"D@=*!! $%,KLLMD%&("+9,3( ' ')"

.GG

"'+ $$#++H3)+ (!"? ''" ++( '", .G.

"+ $$#'+ "(++ !$#@C $%,KLNKD%J,3"

.G/

( +($#(*#)*$(H3* "(!ABC1 .G4

@5%ND3( * $$#" ++( '" '' "()%&"+0'( ABC1( "

.G6

$ '#(!"@&8OLPNLLQD,!*("(("( '" '$#+' .G:

(7)

3 3 1

!" #$%&'("(")(*)+,-./01234567 86 9:;

<"=)<"" > "))?@6(((*!"@1AB.+C)8 9:D

E6 @)FF8G>85@ HIJ"K %?81AB.3L(F(?@ !(*?("

9:M

N< )<!)OF<)"8"@(@*< )<>) 9:P

)6"*)?8"@)F"7?8"@<@"+K<Q>R")48S//B34&("*)?F 99:

" *(?@ ""@!<"?F<"8"@T"6(("N 999

7<+*"74"@8! F")3+-8S//.38FF> "!!

99U

@7)!6F<)"4 99V

WX

Y XW_Z [ XW_Z

\]^_`]^abcdecfg

[hijklmnopqlorsturtvurtowsxysz{|XmY}~

[hjklmnopqlurtvurtowsxysz{|XmY}~

99

EF(@@"(*#$%&4 99

99;

99D

¡ 99M

%)?"(" @@(@?" << "))?"7")"*)4#$%&6"! 7@@*?&<"

99P

¢> ,"")+K" @3"@6"F( ! F@*? "))"F<6"4¹58^1£-8 9U:

£1%#2G!"6 @@6("$ ¤H ¢G¥¦//!<"¦//25R81//25R8 9U9

"@1§S25RF¹58^1£-"@^£1%8!7)?4-(<")(F" >7¨+!!<34 9UU

-!)>"©6 "))"@5 R+5R34¢** 7"6 @! >") 9UV

<)!)?L+>)38@+@*)38+!)38<+<)!)38@@+@*)@*)3444&(

9U

5G2E6 <" @"(-G>")@2 %(?N@)ª'+-G2%'8 9U

«7 ¬@G136("2ET2E"*E!&'®2<">¯*R?) 9U;

")()""<"O"@")"@"<FR"4 9UD

9UM

(8)

9 3 3 1

!!""#$%^&'()*+

,-.

/012314155678269:;3<2:=2=:79;>6<?:32=:7206@?3A2BC29A2:=2DEF/2G6529?H1I2G?<02JKC2LM2 ,NO

G6<172?32DPQ2<;R152SR>63T25:>;<?:324:35?5<1I2?32UC29A2VA7:<6?32?32JKC2LM2:=2G6<17WX2/012 ,N,

5:>;<?:32G652016<1I2;3<?>24:9Y>1<12I?55:>;<?:32:=2DEF/X2JKC2LM2:=264?I?42R;==1725:>;<?:32 ,N-

SZ[\Z]][^Z[\Z]]D6_2KCC29P_2Y[2KXKW2G6526II1IX2/013_262=;51I246Y?>>67824:3<6?3?3A262 ,NN

?3@67?63<2[\F]U25:>;<?:32?32`J]2G652?3517<1I_263I2<012I1A76I6<?:32:=2DEF/2G6529:3?<:71I2 ,Na

R82^\BF2DPQX2/012I1A76I6<?:32:=2DEF/2G652I1I;41I2=7:92<012I14716512:=2<0125?A36>26<2bCXK2 ,Nc

YY92S4:7715Y:3I?3A2<:2<012DEF/W24:9Y671I2<:2<0124:35<63<2dCX\2YY92Y16Te5267162 ,Nf

S4:7715Y:3I?3A2<:2<012[\F]UWX ,Ng

,Nh

&i#jk !lm"%"knop # qm "kj! "#rknm s!

,N.

mt$u!#m ,aO

V25:>;<?:32:=2vd484>:I1H<7?32SZ`vW2?32G6<172SBC29PW263I2625:>;<?:32:=2DEF/2?3291<063:>2 ,a,

SBC29PW2G1712Y71Y671IX2`?==1713<276<?:2:=2R:<025:>;<?:352G17129?H1I2<:A1<0172?32<15<2<;R152 ,a-

S=7:92CwBC2<:2BCwCW_2=:7262<:<6>2@:>;912:=2B29M_2R1=:712=711x1dI78?3AX2/012715;><?3A25:>?I2G652 ,aN

I?55:>@1I2?3<:2B29M2:=2`J]_263I2636>8x1I2R82^B[2DPQX2y:721640276<?:2:=2DEF/2S_2z{X2BW263I2 ,aa

=:7216402Y7:<:32SW2:=2DEF/_2<012@67?6<?:32:=24019?46>250?=<2S|}^?7W2G65246>4;>6<1I2652Sz{X2BWw ,ac

2~2DEF/^SDEF/22Z`v2Sz{X2BW ,af

|}^?72~2}^?7d}^?B2Sz{X2JW ,ag

y:721640276<?:2:=2Z`v2SB7W263I2=:7216402Y7:<:32SW2:=2Z`v_2<012@67?6<?:32:=24019?46>250?=<2 ,ah

|}^?Bd72G65246>4;>6<1I2652Sz{X2\Ww ,a.

|}Bd72~2}Bd7d}C2Sz{X2\W ,cO

/0132|}^?7263I2SB7WX|}Bd72G1712Y>:<<1I26A6?35<2X2Q15;><?3A24;7@152G13<2<07:;A026296H?9;9_2 ,c,

6<2<0122@6>;124:7715Y:3I?3A2<:2<01276<?:2:=2<012?34>;5?:324:9Y>1HX ,c-

(9)

3 3 1

!!"# $$!%!%!$

&'(

)*+,-../01-21/3,0/3.2-32,4-.,/52-13+6,-00/76138,2/,2*+,9+2*/6,/:,;+3+.1<=1>6+57-36,?;+3+.1,

&''

@,=1>6+57-36A,BCDCEF,G,./>H21/3,/:,I;J),13,9+2*-3/>,?K,9LE,-36,-,./>H21/3,/:,MN<O,13,

&'P

4-2+7,?BQK,9LE,4+7+,R7+R-7+6F,N1::+7+32,-9/H32.,/:,2*+.+,24/,./>H21/3.,4+7+,91S+6,412*,

&'T

4-2+7:/7,-,2/2->,U/>H9+,/:,KVV,WXA,-,0/3.2-32,0/30+327-21/3,/:,I;J),?B,9LEA,-36,-,U-7Y138,

&'Z

0/30+327-21/3,/:,MN<O,?:7/9,KV,2/,BVV,9LEF

&'[

)*+3A,91S2H7+.,4+7+,:7++\+<671+6,-36,2*+,7+.H>2138,./>16,61../>U+6,132/,KVV,WX,/:,NQ]A,5+:/7+,

&P^

B=,IL_,-3->Y.1.F,`/7,+-0*,0/30+327-21/3,/:,MN<O,?aMN<ObEA,-36,:/7,+-0*,R7/2/3,?E,/:,

&P&

I;J)A,2*+,U-71-21/3,/:,0*+910->,.*1:2,cd¹aMN<Oe,4-.,0->0H>-2+6,2*-3f.,2/,+gH-21/3,Dh

&Pi

cd¹aMN<Oejkd¹aMN<Oeld¹V,?mgF,DE

&Pn

)*+3A,Bocd¹aMN<Oe,4-.,R>/22+6,-8-13.2,BoaMN<OeF,_+.H>2138,0H7U+.,/5+Y,2/,-,>13+-7,+gH-21/3F,

&P(

)*+,-../01-21/3,0/3.2-32,/:,2*+,0/9R>+S,?pE,-36,2*+,U-71-21/3.,/:,0*+910->,.*1:2.,/:,I;J),13,

&P'

2*+,RH7+,0/9R>+S,?cd¹MRSE,4+7+,6+6H0+6,:7/9,+gH-21/3.,/:,2*+,132+70+R2,-36,2*+,.>/R+,/:,2*+,

&PP

0H7U+.h

&PT

%q,r,Bocd¹MRS,?mgF,KE,-36,$s!q,r,BopFcd¹MRS,?mgF,tE

&PZ

)*1.,9+2*/6,4-.,-RR>1+6,/3,2*+,:/H7,.183->.,0/77+.R/36138,2/,2*+,5H2Y>,0*-13,/:,2*+,I;J)F,

&P[

)*+,:/H7,+.219-21/3.,/:,2*+,-../01-21/3,0/3.2-32,4+7+,-U+7-8+6F

&T^

&T&

&Ti

uvw sx !!"##y!z %wz

&Tn

]3+,91>>1>12+7,/:,5H::+7,./>H21/3,?{=QJ]Do{Q=J]DA,|V,9LA,R=,|EA,B,9X,/:,13*1512/7,./>H21/3,

&T(

?-2,61::+7+32,0/30+327-21/3.EA,-36,BV,WX,/:,}-0f,5+-3,H7+-.+,./>H21/3,?QF~,98o9XA,189-,<

&T'

BKVV,KFKVVE,4+7+,91S+6,13,2+.2,2H5+.,-36,130H5-2+6,:/7,V,913,-2,|,M,?5>-3f,./>H21/3,

&TP

0/3.1.2+6,/:,2*+,.-9+,91S2H7+,412*/H2,13*1512/7EF,G:2+74-76A,B,9X,/:,H7+-,./>H21/3,?t,98o9XE,

&TT

4-.,-66+6A,412*,130H5-21/3,-8-13,:/7,V,913,-2,|,MF,)*+,7+-021/3,4-.,.2/RR+6,5Y,2*+,

&TZ

(10)

3 3 1

! ""#$%&!'())*+,-.,-,-+/&(-!0)-&-1-&

234

5+-&-,-.,--+-/)-+(&&675,8)-50-,+9-+(:

2;<

=>-?!?@AB! ?C!0)-)*/-+(-8-DEF=GC.,(&(5&-,H 2;2

DEF=GCI? J? =KL)MKNC='O!AC 2;P

.)-+-KL)KN+-)-*,+*(-QR)--,5*-,7.).)5)*+7 2;S

+-,/-(1-&6!

2;T 2;U

VWXYZ[\]^[X_`aXab[c\[[bd`

2;e

N-+-88+5&,.)/&6,(()+-,7,/&--)++8 2;3

-8+#Nf07,&5*&g-,&1-75-+(((,.,-1-&/-!h)&- 2;;

,-&6,,.-+-&+-6/+/,-=K*+)7N-,ij+-7?Rk"lm58&,,i 2;4

$-+(:,7?RR?C7#9>7+--,/-(&&6^"?f#9>)-(,-/),/)+5,n 24<

(8(/5,7-+,)-//+56&,81-,+5(5+&+-,5&8/+5(, 242

=o8!C!L+-+(((,&,7),,56.,)-+-+-/-++-(--*5-+

24P

/$B!B1-+-.--:!L.,+,&6*,-+1-))--,6)-&,8&-+&6 24S

Q //,//-+-1+)-+-B"//!p-(&67+-#Nf0(5&*- 24T

--(--+-.--:),-5!9+-1-+7)-)8)-&()-(&,) 24U

(++-,/8)--.&6+-(/5(-*+-:&-,-fn#&:8-7 24e

,5*,5-*6fnq*!0),+-,5&.,,5*,-O5-&6(/&---(++*+-*6 243

)8)+-,&5,,,/-(+-+6=$>9pC&6,,=o8!C!L--7./-:,Mg???!BQ 24;

A"!kA//-+-7)5,-,+8)-//+/),/)+((=mK0fC 244

En*56&-7+-,/-(1-&6!0),,).-)-1+-(&-18-*-.--)-f)- P<<

#-(-(-)-*56&()7*)fn#$&:8-,+-8,*&-!9+-1-+75-+

P<2

)-(,5,-7#Nf0q.,*,-+1-!0)-,))-fIp*,*&-5-+

P<P

(,5,-)pMq-r()8-((5+,&6,&,7/+**&6):,*(-+&

P<S

(11)

3 3 1

!"#$%%&'%("#)#'&)%%(*+,-%#&%#.##/ %.#)01% 234

1"%."(% %.#)(&1%&)#&/#156778/9::;<=^>^?@=A;<=^>^?1^>^<!9<7BC##

23D

C055 #$#&$#&1E 23F

23G 23H

23I

JKLMNOMN8PE^Q<,*RS$%%&')8+E6SRC 11%("#)#'&)%%(*+,-56 2T3

77 2TT

2T2

(12)

3 3 1

!"##$%&'(!()!#"*'#!*"(("'#

+,-

!.(" !"#'.!")(!!(."# !#/0"%!.!($1234 '(! &(!!

+,5

"(#!("! !(6!*76("'#$#*!6(#'(!!!#"!8!(!#!(!#*""6 +,9

&'""'(!!/:!*"&"&"( "#)";! #)*"&

+,<

)"(#!$%!&('#!#((6!=>6/?@$%!7"%(*"#(!!8(!#

+,A

&(" (!#!%!!#BCDEDFCGHIJI/K;#L;M((6!(!(!(N!#*!O'!!"&P; +,Q

6")("=P;RF@(!#'!.6!(.!^SMT#^TMS"&"( "$!!(

+,U

(!'6&(" ?$V;#(";*(#6!$#!#")#"'*!(#"&"( "/W;

++X

M((6!(!"*'"&'&!#P;RF!!$*'#&&!(&(" !!(& !* ++,

!*!!"&#(";*(#6!#*!' *!("&"6("')$'(!'6!(( +++

(**"(''(!=M'$YZZ[@/P!)!!((6!$((6!(!*!"!(% ++-

."!" )"'#=0 *!"$>*($P!*!'&"($P'(;2('\]"!$YZZ^@/! ++5

')"!N!#"'#)"*!(!!(%!*'"&1234$!.!

++9

%!7$"("%! "(!)"()")"( #!)("&!*"($"(*"&'"/: ++<

*$!'#!#*"(%#".!#'(!#"'""&K;$L;"(W;((6!

++A

*'&&!(!#)0[/[/_#!6(#"% ""(!#*^?T31`a#" )(!#""&1234 ++Q

&"( '!#b6("/c&"('!$")("!6!&&!%"*!(.!##! ++U

#))!(!"&1234(*"#(!"'"".!()!("#"&V#&""%!#7! +-X

" )(*!%"&" !(.*!&"( '"=d!!d'))! !(`!(@/ +-,

(13)

3 3 1

!!"

# !!"

$ !!"

%&%

'()*+*,-./01.2,34.5645.73,89,:;,#:;,1<=,$:61..1>?7<1<3@

%&&

%&A

B<,1,3768<=,341>7;,1C>/<1473,D7.7,1C38,4./7=,48,E847<4/1CC2,61..2,4?7,41.>74,4?/8E?83E?8.10/=7@,

%&F

G3,61..1>?7<1<3;,4?72,E.737<4,1</8</6,>.85E3;,/@7@,61.H8I2C1473;,H54,<84,35C91473@,J7,4?53,

%&K

1<4/6/E147=,4?14,61.H8I2C147,>.85E3,/<,1C>/<1473,685C=,L57<6?,3807,E.848<3,9.80,4?7,07=/1;,

%&M

4?53,E.7N7<4/<>,OP-Q,?2=.8C23/3@,R8.78N7.;,S:>5C5.8</6,7<4/4/73;,H54,<84,T:01<<5.8</6,

%&U

.73/=573;,012,98.0,61N/4/73,D?/6?,61<,1668008=147,=/N1C7<4,614/8<3,356?,13,61C6/50,VW/>@XY@,

%&Z

Q?53;,/<,4?7,E.737<67,89,61C6/50,31C43;,4?7,E8C2>5C5.8</6,6?1/<3,>14?7.,1.85<=,614/8<3;,

%A[

6.714/<>,1,<74D8.\,89,6?1<<7C3,D/4?,3807,916/1C,10E?/E?/C/6/42@,J7,?1N7,?8D7N7.,8H37.N7=,

%A]

<8,3/></9/61<4,/0E.8N707<4,89,4?7,98.05C14/8<3;,53/<>,1C>/<1473,1C8<7,8.,4?737,

%A%

E8C23166?1./=73,/<,4?7,E.737<67,89,61C6/50,31C43,48,E.8N/=7,H71=3@,Q?7,C1447.,61<<84,.741/<,

%A&

799/6/7<4C2,4?7,OP-Q,08C765C73,3/<67,4?72,=/99537,/<48,4?7,1L57853,38C54/8<,D/4?/<,8<C2,1,97D,

%AA

0/<5473@

%AF

(14)

3 3 1

!" #$ !"

^% ^%

^%

&'(

)*+,-,./.01231456781269.51:;9.314.69<8267;=>

&'?

&'@

AB;=;.4;=C97=.9;:.C=.71.7C42.71.2;C7469.D19E=600B648:;=>./<64.D4;=;27.7;47864E.012314567812=.

&'F

091=;.71.7B67.13.GH.62:.IH06446<B;262=J.965826482;=K.69=1.0699;:.LHMNKOPH<9C062=K.062.14<628Q;.

&RS

82.748D9;.B;98TK.62:.U6=.694;6:E.C=;:.71.<C8:;.7B;.=E27B;=8=.13.BE:41DB1V80.2621567;4869=.

&RW

MX;B71Y6646.Z.[CK.\]NNJ.^1C2<K._12<.Z.`601V=K.\]]]PJ.=7640B.U6=.69=1.=;9;07;:.=820;.87.8=.

&R&

U;99.;=76V98=B;:.7B67.87.062.;206D=C967;.81:82;K.98D8:=K.=C43607627=.VE.314567812.13.8209C=812.

&Ra

015D9;T;=.Mb;82;5622K.c=0B;4.Z.d12:;He;787K.\]]OP.Mf8<>gP>.h20;.6<682K.21.=76V898Q67812.

&R'

U6=.1V7682;:.C=82<.V17B.6<64.62:.965826482;=>.i;Y;47B;9;==K.6.=98<B7.85D41Y;5;27.U6=.

&RR

1V=;4Y;:.C=82<.=7640B.D4;Y81C=9E.C2=74C07C4;:.82.6.V18982<.6jC;1C=.=19C7812>.k2:;;:K.l]m.13.

&R(

ineA.4;5682;:.C20B62<;:.637;4.282;.:6E=.UB89;./<417682.U6=.:;015D1=;:.67.l]m.1Y;4.7B;.

&R?

=65;.D;481:>.o;.BED17B;=8Q;.7B67.7B8=.D1=878Y;.;33;07.062.V;.6==8<2;:.71.7B;.D4;=;20;.13.

&R@

B;980;=.7B67.D4;38<C4;.569710E091:;T7482=>.

&RF

(15)

3 3 1

!"#$%&'

()&*

+,-

./01213456789:;:<=67>=?74@4?A7BCDAEFB@;GH468746I78<4?HJK +,L

+,+

MJ:?:>=?:A7<J587?:8G;<7:6H=G?4@:I7G87<=7G8:7NG?:7HOH;=I:P<?5687568<:4I7=>7N=;O84HHJ4?5I:8A7 +,Q

856H:7<J:O74?:7H=RR=6;O7G8:I7567<J:7NJ4?R4H:G<5H4;756IG8<?O7SG<74;8=7567<J:7>==I746I7N;46<7 +,T

J:4;<J7>5:;I87CUJ:6A7V46@A7W46@A7XJ=G7Y7ZJ:6A7[\D[FK7W:7:PN:H<:I7<J4<7<J:7;5N=NJ5;5H7H4]5<O7 +,^

=>747HOH;=I:P<?56756<:?4H<7_5<J7<J:7`abM7SG<O;7HJ4567<=7>=?R747H=RN;:P74S;:7<=7N?=<:H<7<J:7 +,,

56J5S5<=?7>?=R78G??=G6I56@74H5I5H7R:I5GRK7c<7_487>5?8<;O7:485;O7:8<4S;58J:I7<J4<7<J:7R=?:7 +,d

8G5<4S;:7HOH;=I:P<?567;59:;O7<=7>4]=?4S;O756<:?4H<7_5<J7`abM7_487<J:78R4;;:?7=6:7H=6<45656@7 +,e

85P7@;GH=8O;7?:85IG:87CfBHOH;=I:P<?56A7ZgBfF7Ch5@K7@5]:67567UGNN;:R:6<4?O734<:?54;FK7 +,i

U:H=6I;OA7<J:7=N<5R4;7R=;4?7?4<5=7ZgBfj`abM7_487:PN:?5R:6<4;;O7I:<:?R56:I7487DkDA746I7 +d-

h5@Kl8J=_87<J4<74<7;:48<7m\n7=>7`abM7?:R456:I78<4S;:74><:?7>=G?7I4O874<7No7pKpA7_J5;:7l\n7 +dL

=>7`abM7>?=R7q@?=<4567>=?RG;4<5=67_487JOI?=;Or:I7G6I:?7<J:784R:7H=6I5<5=68K7MJ587 +d+

H=??:8N=6I87<=746756H?:48:7=>7mpn78<4S5;5<O7 +dQ

+dT

(16)

3 3 1

!"#$#%&'()**#+, $-#./0#!++#12345&'()6 789

78:

; $!!<=./>+/* ?/$@+/#%./?@?>/*/,*#0>!/AB?,//+0 $/,<^CD&EF.$G?#./

788

H#I?>!#0/.#,JE+K#$=E. +#$=( !+,=L/0 +/3D@+/!=2@/!/M2N/, $ 3( !+,=

78O

PQQRS6). ?>>+#*. ??/,#$./*#++/!#$/B//$./*#0>!/A*#$*/$+#$ $ 78T

?#!@#$$,./*./0 *!?. %U+#$?#%>+##$? $#../.#?J1234S$,./-@/?

7OV

J&'()W?//@>>!/0/$+<E/+!S6E#+/>+*@!+!<=./*#0>!/A*#$*/$+#$ ? 7OX

>+#>#+#$!#./YZ[6\[B./+/YZ[*#++/?>#$,?#./*./0 *!?. %U+#$%#+>+##$[ 7O7

$,\[ ?./+#]&'()^5J]&'()^_]1234^S6'/*@?/#%!#BU+#$?#?/+U/,%+#0 7O`

>+##$?#%1234=./H#-+>. *B?,+B$%+#0? -$!?*#++/?>#$, $-#./@<!*. $ 7Oa

J; -6bS6cCdC*#0>!/AB?.@?@$0 -@#@?!</?!?./,6 7O9

7O:

ef2//+0 $#$#%./1245&'()**#+, $-#./H#I?>!#0/.#,JE+K#$=

7O8

E. +#$=( !+,=L/0 +/3D@+/!=2@/!/M2N/, $ 3( !+,=PQQRS6D3D,+/%#+./!G<!

7OO

*. $#%&'()$,Dg%#+./1246 7OT

(17)

3 3 1

!"## $%&'(#)*+,*- %.&(/01234561(-(,&#"#78"9:;<"-%

=

"%- ">&+)"#*,)$,("- () "-#. '- !"-!"."(-%"#,"9(-%:/!#$,"-9

#+) $*),(,&# (.,"#!%!( ?0@>!*(,)&),%A "-(),#!!&,*"-(, B

9$+>!(,C&,)!("->6DE/(-%!( ?0F>!>*A+#%>*!."99)'- G

)$,%"- () '"!(,,+-#>!.$ &,)!("-.$ *+(")$,(,&'"!!)H?I: J

K

L

MNOPQRP8)$#-61/012345#+) $*>!"-),$#"-)*+,AHSTU6DE/:

V

8"-(,,&"-%)!(() "W !%&-(*")>!X$","."$*!(##)"( "-)-# (- YZ

B

'(#% *"-%())%"-9 !D-#"0?",%.(-%* !%(++,"%-^[?61#"9-(,# B=

)#+-%"-9 !.$ &,)!("->!6DE/7D-#"\?",%.(-%[]^]<:_#"-9(,(9 B

A)##>HS0T(-%()-# (- )-)- ( "-"-6DE/(,,#$,"-9# ("9! #)#+-%"-9 BB

!+-#>6DE/9(((,$>]^`^⁰^[#,"9! ,&"->(>!>*( "->! BG

)*+,A:

BJ BK

(18)

3 3 1

!"#"$"%&&'(#)!"!#*(%&$#) +,-

(%"#$ %./%0&12341567 8'0&)# $%"#&#*#)"!#*

+,9

:";(0)<=%0#*><?@A/#(&'<<>?$)BC?D#**) +,E

FGHIJ>DDAK<=. "&'%##*FGHI(!LM"!"%#&.)/""#$ &(!

+N,

*"&")#*( )# )!'(0%#/)"!#( 0# +NN

) "/")&(%!#)$ ?<?&/*"$ %"!#*

+NO

*#)$0%#<I#"#"%0&0&!'>P>"%0#"#$ %./%%#%0##*CQM +N+

LRFGHI/.""!"%#&.)J)#PSP>&?P>K/)& #&#"&"#%<

+NT

A##)#*0)"#")##/&$ %/*#)$0%#&$%) +NU

**""!#*=)#JVV0 %$)!A)%K<V""!12341567/

+NW

$#))*#)"#$ %.'%$#"#0%&()(0&#(")%"!*)#$

+N-

#%<

+N9 +NE

XYZ[\]^_`ab\]

+O,

c0)0&! )#*"0)))&#*#)$0%(#""#$ #0&' "%%!*%&

+ON

#*)"0%0)'$ % #(%0%$0$()#*&&'#(#0%! +OO

)#$%%!*)&%!<B"#.'/*#)$0%##*FGHI'0)(#) +O+

/&%!0&*)%d)'/)"&/$#%#*")(%!#)$ +OT

0&)"&""#&#<c0) )#"/(&#$#%"0%)")")"#*

+OU

# # #)$&" ) #%) # #)$&*0"#&% # %"(0!%

+OW

"<I)*#)' %#* #%!"")&'0)%#)")&'/&**) +O-

!"#"$"% )# )'/&<F)%'()0%/)#(&/ +O9

LM"!"%#&.)0&&&<I>P>"%0#"#$ %./*0%%!")")d&&

+OE

)&$#&)(#"!J><?@AK(0*"")&(%! ?<? ++,

"#$ )&##*"#$$)"%=)#J8?e*)f&!K<I)0%"%0#"#$ %. ++N

(19)

3 3 1

!"!!#!$!$%&'())"*+&***""+*$ ,,-

! !*"&*".)/+0123*"$"/%*45!.%*!*++"*"$

,,,

!*(#%*' ,,6

,,7

89:;<=>?@>A>:BC ,,D

E2%$#%+&!FG#*1%#*HIJ*H*F**KG%)+%2!E ,,L

+ !)'3!)%*%&%)%+!(MNO3IKPF)%Q"H %$!2R ,,S

T.)GUGK%1%#**&))%$!3IK(T(#%I*%**VW%&) ,,X

F&%Y'3!&!%!*Z[*42&W&G#*VP0OTFY+%0KF%"%*#' ,6\

,6]

^>_>`>:a>C ,6-

bcdefeghijkilkhimnopqohirkiskhitiuedvwonhixkiy]XS,zki{|o}fnpwpieovi~vn~noveo}ip}ecww|iqi~dwonD

,6, pnowiewvhiei~}e}wnidne}wnign}ecqw}niqiD}fwq~dwonkihi]7-,]7-Dk

,66 mnonpwhikibkhitiwvncdeovhiukikiy]X6Xzkibip~n}dq~fq}qgn}dwiwonp}we}wqoiqi}fniwo}nde}wqoiqi ,67 wqvwoniw}fiedqge}wif|vdqedcqopkihi-L\,-L\Lk

,6D whi{kikiy-\\7izki ¡¢£¤¢¡ ¥ ¢¤¦¥¥¡¤¢§¥¥¦¤¡¤§¢k

,6L ¨qg©onªhiskiukhi{eoged}©ohikhi«qo}hiskhi¬eq~hiukibkhi{eoi«deowpqhi{khidd}wehi®khiqvppnhi«khiti ,6S ¯ed©eswoehiukiskiy-\\Szki¨npwohip|o}fnpwphieovicwqqweinee}wqoiqi~fqp~fqdegwvnivndwe}wnpi ,6X epidnepniwofwcw}qdpki°¤±hi,L-],L,]k

,7\ ¨qepphi²kibkhitinovdw³pqohirkirkiy]XX]zki¬rign}fqviqdi}fnieoe|pwpiqi}fnidnepniwofwcw}qdi´

,7] yoc}|z}fwq~fqp~fqdwi}dwegwvnieoviw}pign}ecqw}npki°¤µ¶hi-,]S-,-]k

,7- «qo}hiskhi¨qgwonªhiskukhi{eoged}wohikhi¬eq~hiukibkhi{eo«deowpqhi{khidd}wehi®khiqvppnhi«khiti ,7, ¯edweswoehiukiskiy-\\Szki{}d}deifede}ndwp}wpiqi¬fqp~fqdegwvni¨ndwe}wnpiepidnepni ,76 xofwcw}qdpkijn·wdngno}piqdib}ww}|ki°¤±y]SzhiS67]S6D\k

,77 egcn}qohibkhi«ecdehiskukhi¨ncneqd}hi«khi¨d|mdohikhiti¸qwn|hibkiy-\\Xzkixo}ndenieoviedqgei ,7D ceddwndi~dq~nd}wnpiqiwq}eeddennoeoingpwqocepnviwgpipnviqdinoe~pe}wqoiqie}wniqqvi ,7L qg~qovpki¹§°¶µy]zhiS\SSk

,7S nwongeoohikhi²pfndhi«khitiqovn¬n}w}himkiy-\\,zki{}d}deine}dnpiqip}edfe}qoniwopwqoi ,7X qg~nºnpiwoie·nqpi~q}e}qip}edfivwp~ndpwqopi»i}fnidqniqieg|qpnieovieg|q~n}woki ,D\ ¼¦ ¢hi]7X]DSk

,D] ½qhiuki«khi{ndvqhiski¨khijqwhiskiskhinovdw³pqohirkirkhiti¸eoi¨ndi¬|hiskiy]XS7zk¾¼¡§¡ ,D- ¿±µÀ¿k

,D, rnf}qeedehimkikhiti¯hi«kiÁkiy-\]]zki¬fedgeqqwehip}d}dehieovivdivnwnd|i~dq~nd}wnpieovi ,D6 e~~we}wqopiqi]h,cn}eeopki°¤±¶hiDS],DS-Sk

,D7 rnwo³ndhiskhijnwofedv}eowpfhibkhied}ohi²khitiqoimqdnhi²kiy-\\7zkijnvwoieggqoweingwppwqopi ,DD c|ipwoidnepniwofwcw}qdpkiÂ§¡§¤Ãhi,6-,6,k

,DL sedÄqohi«khise}fwdqohi¨khi¬wedvhi{khirngewdnd}nhibki{khi¨cennhiukiskhiti¨Ånvewow¬wedvhi«kiy-\\Xzki ,DS ¨nnq~gno}ieoviqdge}wqoiqiei\k-Æiqdeipq}wqoiqigwveªqegiqo}ewowoi|qvnº}dwokiÇ§¡ ,DX ¼¶hi-66-7\k

,L\

(20)

3 3 1

!"#$%&'(()*+,-.,/,01-,234,35,6,-2.74/2.402.348.29:0-,23;<=;>%";?@

AB' $C

AB) D%E%C#F"#G#<H;=#I#G=%@>J;#K=>F%K;L $%<M#%%NE ABA OK=L@>!P%%=Q%R&)S')*TUV;W<XGNWN;<=VJN=W@WJU=W;;?$=G=W;

ABY V%V%<=X=<%=X=W;<==J=$=<%Z[-.15[9.23\4]^BS(_@B'S)

AB_ HJ>O;G` ;GOaJ#L!>J>&)S')*>UVb;<=XW;V;=W=c=<Jde@ ABf WNW?b<%=<=UV%KV<=W=?X%U#;<=gXXW<;h###$==<N?=#<=%;<

ABB <;$==<N;?=;?%V<=ij4k30lj4m5[32nj4o10.20p0lj4q5[nj\4rs&A@Y*)fA@)BY

ABt H#$$;%;uRT<MH;J%;c;vwx%%N w;C;J;%;vTJ=C;c;y ;<;;$y AB( H#;G;vI?F!I;TF&)SSf*HWV;?<%;<G=X%%G#;<=X=<%=X=W;<== AtS ;G%=W#<#%;N<U@>J;G;?VV%<#=<=q.,-j4z[{j4ml13-4|0,j\4s}ASA@AA_

At' H#U%Lx&'()f*yJ=;<=;?W%N<;=~;<=X<J~NU#%;ij4,2lj4q5[njYA_@YY' At) y%CF&)S'S*|l241394023-.2l[9.[l[17[413947-16,l,[94/[.-,l,[.7j43428-,234/2.4[35130,34 AtA 3:-.,[3-4:7[4[//,0,[30p4,341.,0:l-:.[T<%;<=;X%<==~%=?#<%N;W=;<=

AtY O#GH@"G @L!L;W$II&)SSS*M$%K;<=X;V;%<=;NV?<%=V@J=b At_ WX%U;<=='A@$<;@G#W;$NX#%WW%;W%GN<%;X%VW<%WVNij4,2lj4 Atf q5[nj\4sr}''tBY@''tB(

AtB a;U;FG#NFwx%J;<<L!#=xP&)SSt*I?#W=G"A)M;?MA@ Att X%U;V;<#%=c=<J#%;%=<%=X=W;<==J=$=<%;?U<;H@;U??

At( =<%G#X%<==~%,2lj4[.-,lj4|2,l7\4f(A@BS_

A(SA(' A() A(A A(Y

(21)

3 3 1

!"

# "!_$

% "!_$

&'()*'(+,-./-01

%23456789:;69<=>?<>@?<>9A=BC=DEF"7#GH

%2I456789:;6?<>@?<>9A=BC=DEF"7#GJH K

LMNONPQRSTURTSVPWXPRYVPZRT[\V[PTSV]ZVP\^Y\_\RWSP`abcd e

f

(22)

3 3 1

!^"#$!%&'!()*+,)-+*.!/*0!1 !2+.3!'45)67,+)*!&/55!894:,-)(4,-;!/*/6;5+5!)<!,34!

04.-/0/,+)*!)<!%1$=!/,!92!>?>?!

@AA

@AB