Syn hesis, s uc u e and an i- ungal ac i i y o dime ic
Ag(I) complexes con aining bis-imidazole ligands
Suaad Abuskhuna
a
, John B iody
a
, Malachy McCann
a,*
, Michael De e eux
b
,
Ke in Ka anagh
c
, Julia Ba ei a Fon echa
d
, Vickie McKee
d
a
Depa men o Chemis y, S . Pa ick’s College, Na ional Uni e si y o I eland Maynoo h, Maynoo h, Co. Kilda e, I eland
b
Dublin Ins i u e o Technology, Ca hal B ugha S ee , Dublin, I eland
c
Depa men o Biology, Na ional Uni e si y o I eland Maynoo h, Maynoo h, Co. Kilda e, I eland
d
Depa men o Chemis y, Loughbo ough Uni e si y, Loughbo ough, Leics LE11 3TU, UK
Recei ed 10 No embe 2003; accep ed 4 Feb ua y 2004
Abs ac
Fi e Ag(I) complexes con aining he ligands bis(imidazol-2-yl)me hane (2-BIM) and i s de i a i es we e p epa ed and [Ag2(2-
BIM)2](ClO4)2and [Ag2(2-BIM(Bz)OH)2](ClO4)2E OH we e cha ac e ised using X- ay c ys allog aphy. In each dime he wo
Ag(I) ions a e wo-coo dina e and he e a e small bu defini e a gen ophilic Ag–Ag (d10–d10) in e ac ions. All o he complexes
display an i- ungal ac i i y when es ed in i o agains he ungal pa hogen Candida albicans.
Ó2004 Else ie L d. All igh s ese ed.
Keywo ds: Bis-imidazole; Bis(imidazol-2-yl)me hane; X- ay s uc u es; Sil e (I); A gen ophilici y; An i- ungal; Candida albicans
1. In oduc ion
In ou effo s o de elop new me al complexes ha
would g ea ly inhibi he g ow h o he human ungal
pa hogen Candida albicans [1–4] we ha e ound ha , o
da e, he mos ac i e d ug es ed in aqueous media is he
Ag(I) complex [Ag(phendio)2]ClO4(phendio ¼1,10-
phenan h oline-5,6-dione) [5]. As pa o hese ongoing
s udies in o he syn hesis and in i o es ing o new me al-
based an i- ungal d ugs we epo he e he p epa a ion o
fi e Ag(I) complexes con aining bis(imidazole) ligands.
Bis(imidazol-2-yl)me hane (2-BIM) and i s de i a i es
(Fig. 1), in which he wo imidazole ings a e linked ia a
single e ahed al ca bon a om, can be iewed as p imi i e
models o mul i-his idine coo dina ion in biological
sys ems. Such bis(imidazole) ligands ha e been shown o
o m s able six-membe ed chela e ings wi h a a ie y o
ansi ion me als [6–12], and he P (II) complex [P (2-
BIM(Me)OH)Cl2] (2-BIM(Me)OH ¼bis(N-me hylim-
idazol-2-yl)ca binol) [10] has been epo ed o exhibi
no able an i umo ac i i y.
2. Resul s and discussion
In he cu en s udy, AgClO4was eac ed a oom
empe a u e wi h me hanolic solu ions o he fi e
bis(imidazole) ligands shown in Fig. 1 o gi e he e-
spec i e Ag(I) complex in mode a e o good yield. The
complexes we e soluble in ho ace oni ile and DMSO
and insoluble in wa e . The X- ay c ys al s uc u e o
[Ag2(2-BIM)2](ClO4)2(Fig. 2 and Table 1) showed he
complex o be cen osymme ic, con aining wo Ag(2-
BIM)þuni s. The wo me al ions a e wo-coo dina e
and ha e iden ical a oms in he plane o he chela ing
ligand. Using i s wo imine N a oms each 2-BIM ligand
b idges he pai o Ag(I) ions. All ou N a oms (N1,
N4A, N4, N1A) a e coplana and he wo imidazole
g oups in each 2-BIM ligand ha e an in e plana angle
o 75.52(8)°. The wo Ag(I) ions a e only weakly in e -
ac ing, he dis ance sepa a ing hem being 3.2612(4)

A.
The binding o he wo 2-BIM ligands is simila o ha
*
Co esponding au ho . Tel.: +353-1-708-3767; ax: +353-1-708-
3815.
E-mail add ess: [email p o ec ed] (M. McCann).
0277-5387/$ - see on ma e Ó2004 Else ie L d. All igh s ese ed.
doi:10.1016/j.poly.2004.02.006
Polyhed on 23 (2004) 1249–1255
www.else ie .com/loca e/poly
obse ed o he Biim2ligand (Biim2¼2,20-biimidaz-
ola e) in he he e opolynuclea complex, [{Ru(pap)2
(Biim)}2Ag2](ClO4)2H2O (pap ¼2-(phenylazo)py i-
dine) [13]. The sho e Ag–Ag sepa a ion in he la e
species is (2.8899

A) is mainly a consequence o he
smalle size o he Biim2ligand compa ed o 2-BIM
(no me hylene b idge be ween he wo imidazole ings in
Biim2). The o mula uni o [Ag2(2-BIM)2](ClO4)2is
comple ed by wo la ice pe chlo a e, which a e in ol ed
in hyd ogen bonding o he hyd ogen a oms o he im-
idazole ni ogen a oms (N2 and N3, and N2A and N3A,
espec i ely). The la ice pe chlo a e anions show un-
symme ic b idging in e ac ions wi h Ag(I) ions o
neighbou ing ca ions (AgOClO32.965(2) and 3.264(2)

A). The e a e hyd ogen bonding in e ac ions along he a
and bdi ec ions which link he uni s oge he in he
la ice, o ming shee s. Howe e , he e a e no hyd ogen
bonds in he cdi ec ion, ha is o say, be ween he
shee s. The e a e some in e molecula p–pin e ac ions
in ol ing he imidazole ings on adjacen dime mole-
cules and he e is also e idence o some in e dime
C–Hpin e ac ions be ween neighbou ing imidazole
unc ions. A pe spec i e iew o he cell packing is
shown in Fig. 3.
The X- ay c ys al s uc u e o [Ag2(2-BIM(Bz)-
OH)2](ClO4)2E OH (Fig. 4 and Table 2) shows he
asymme ic uni con aining one [Ag2(2-BIM(Bz)-
OH)2]2þuni , wo pe chlo a e anions and a sol a e
e hanol. The wo Ag(I) ions a e again b idged by he
wo ligands and each me al is app oxima ely linea ly
coo dina ed o a pai o imine ni ogens. The e a e ad-
di ional longe in e ac ions wi h he pe chlo a e anions.
The me al-me al dis ance o 3.018(4)

A is conside ably
sho e han in [Ag2(2-BIM)2](ClO4)2. Wi hin he
[Ag2(2-BIM(Bz)OH)2](ClO4)2E OH complex molecule
he e appea s o be some deg ee o in amolecula p–p
in e ac ion be ween he imidazole and phenyl ings o
he opposing wo 2-BIM(Bz)OH ligands in he dime .
In e es ingly, he angles N(1A)–Ag(1)–Ag(2) and
N(4B)–Ag(1)–Ag(2) a e e y diffe en o one ano he
(168.30(12)°and 68.35(8)°, espec i ely). One o he
pe chlo a e anions in he complex is diso de ed and was
modeled wi h wo al e na i e se s o oxygen a om po-
si ions (50% occupancy each). The e hanol sol a e is
also diso de ed and was modeled as 50% occupancy o
wo al e na i e posi ions. Hyd ogen a oms a ached o
ca bon we e inse ed a calcula ed posi ions, whils
hose a ached o he 2-BIM(Bz)OH alcohol g oups
we e loca ed om diffe ence maps and no u he e-
fined, hose bonded o he diso de ed oxygen a om o
he e hanol sol a e we e no loca ed o included in he
model. One iew o he packing in he c ys al is illus-
a ed in Fig. 5.
Repea ed a emp s o g ow c ys als o [Ag2{2-BIM
(Me)}2](ClO4)2, [Ag2{2-BIM(CN)}2](ClO4)2and [Ag2{2-
BIM(BzCl)}2](ClO4)2sui able o X- ay s uc u al anal-
Fig. 2. X- ay c ys al s uc u e o [Ag2(2-BIM)2](ClO4)2.
RR'
2-BIM H H
2-BIM(Bz)OH PhCH2 OH
2-BIM(Me) Me H
2-BIM(CN) NC(CH2)2H
2-BIM(ClBz) Cl2PhCH2 H
N
N
N
N
HR'
R
R
Fig. 1. Ligand symbols and s uc u es.
Table 1
Selec ed bond leng hs (

A) and angles (°) o [Ag2(2-BIM)2](ClO4)2
Bond leng hs (

A)
Ag(1)–N(4)#1 2.0953(17)
Ag(1)–N(1) 2.0957(17)
Ag(1)–Ag(1)#1 3.2612(4)
Ag(1)–O(11)#2 2.965(2)
Ag(1)–O(11)#3 3.264(2)
Bond angles (°)
N(4)#1–Ag(1)–N(1) 167.80(7)
N(4)#1–Ag(1)–Ag(1)#1 91.08(5)
N(1)–Ag(1)–Ag(1)#1 99.94(5)
Symme y ans o ma ions used o gene a e equi alen a oms: #1
xþ1;yþ1;zþ1; #2 1 þx;1þy;z;#31x;y;1z.
1250 S. Abuskhuna e al. / Polyhed on 23 (2004) 1249–1255
ysis we e unsuccess ul. Howe e , gi en he close simila -
i ies in he co e s uc u es o all fi e bis(imidazole) ligands
he la e h ee sil e complexes a e hough o be essen-
ially isos uc u al wi h [Ag2(2-BIM)2] (ClO4)2and
[Ag2(2-BIM(Bz)OH)2](ClO4)2E OH and a e hus also
o mula ed as dime s. Fo [Ag2{2-BIM(CN)}2](ClO4)2
he e is also he possibili y o he pendan cyano g oups
pa icipa ing in he bonding o he me al since Ag(I) has a
high affini y o o ganoni ile dono s.
2.1. In i o an i-Candida s udies
All o he me al- ee bis(imidazole) ligands and he
Ag(I) complexes we e sc eened o hei abili y o inhibi
he g ow h o C. albicans. The minimum inhibi o y
concen a ion (MIC) is he concen a ion o d ug (ex-
p essed as lg o complex pe 1 cm3o aqueous g ow h
medium solu ion) equi ed o o ally inhibi he g ow h
o he ungal cells a 37 °C. As he complexes and he
Fig. 4. X- ay c ys al s uc u e o [Ag2(2-BIM(Bz)OH)2](ClO4)2E OH.
Fig. 3. Packing diag am o [Ag2(2-BIM)2](ClO4)2.
S. Abuskhuna e al. / Polyhed on 23 (2004) 1249–1255 1251
ligands we e essen ially wa e insoluble he es s we e
ca ied ou as suspensions o he complexes in he
aqueous g ow h medium. In addi ion, because he
complexes we e soluble in DMSO a se ies o an i- ungal
es s we e also conduc ed using DMSO/wa e solu ions
o he complexes (see Sec ion 3). In all cases, he ac i i y
o he complexes we e compa ed o ha o a con ol
sys em in which he cells we e g own in he absence o
any added complex o ee ligand (unde hese condi-
ions he ungal cell eplica ion was apid). In addi ion,
unde he p esen biological es condi ions an aqueous
suspension o he an i-Candida p esc ip ion d ug ke o-
conazole had an MIC alue o ca. 2.5 lgcm
3.
All o he me al- ee ligands we e ound o be inac i e
agains he ungal cells. As aqueous suspensions, he
sil e complexes we e mode a ely ac i e wi h MIC alue
anges indica ed in b acke s: [Ag2(2-BIM)2](ClO4)2(10–
20 lgcm
3); [Ag2(2-BIM(Bz)OH)2](ClO4)2E OH (50–
100 lgcm
3); [Ag2{2-BIM(Me)}2](ClO4)2(20–50
lgcm
3); [Ag2{2-BIM(CN)}2](ClO4)2(20–50 lgcm
3).
A conside able imp o emen in an i- ungal ac i i y was
obse ed upon adminis e ing he complexes as DMSO/
wa e solu ions as opposed o aqueous suspensions:
[Ag2(2-BIM)2](ClO4)2(5–10 lgcm
3); [Ag2(2-BIM(Bz)-
OH)2](ClO4)2E OH (2.5–5 lgcm
3); [Ag2{2-BIM
(Me)}2](ClO4)2(2.5–5 lgcm
3); [Ag2{2-BIM(CN)}2]
(ClO4)2(5–10 lgcm
3); [Ag2{2-BIM(BzCl)}2](ClO4)2
(5–10 lgcm
3). Besides g ea ly inc easing he solubili y
o he complexes he DMSO is also hough o make he
cells mo e pe meable o he complexes so ha hey can
en e he cells and exe hei effec s on he o ganism. In
compa ison, as an aqueous suspension [Ag(phen-
dio)2]ClO4has an MIC alue o 0.3 lgcm
3[5].
3. Expe imen al
Chemicals we e pu chased om comme cial sou ces
and, unless specified, we e used wi hou u he pu ifi-
ca ion. Li e a u e me hods we e used o p epa e 2-BIM
[14,15], 2-BIM(Me) [7,16] and 2-BIM(OH)Bz [17]. The
p epa a ion o he sil e complexes was conduc ed in he
absence o ligh and he samples we e s o ed in he da k.
In a ed spec a o solids (in a KB ma ix) we e e-
co ded in he egion 4000–400 cm1on a Nicole FT-IR
Impac 400D in a ed spec ome e and 1H NMR
spec a we e un on a B uke A ance 300 MHz ins u-
men . Mic oanaly ical da a we e p o ided by he Mi-
c oanaly ical Labo a o y, Na ional Uni e si y o
I eland, Co k, I eland.
3.1. 2-BIM(CN)
Ac yloni ile (3.6 g, 67 mmol) was added o a mix u e
o 2-BIM (5.0 g, 34 mmol), and ie hylamine (6.8 g, 67
mmol) in ace oni ile (150 cm3). The eac ion mix u e
was efluxed wi h s i ing o 5 h. The sol en was e-
mo ed unde educed p essu e gi ing a whi e solid,
which was ec ys allised om ace one. Yield: 4.7 g
(55%). Mp 170 °C. Anal. Calc. C, 61.40; H, 5.50; N,
Table 2
Selec ed bond leng hs (

A) and angles (°) o [Ag2(2-BIM(Bz)OH)2]
(ClO4)2E OH
Bond leng hs (

A)
Ag(1)–N(1A) 2.111(3)
Ag(1)–N(4B) 2.134(3)
Ag(1)–Ag(2) 3.0184(4)
Ag(1)–O(11) 3.211(6)
Ag(1)–O(13) 3.312(7)
Ag(2)–N(1B) 2.119(3)
Ag(2)–N(4A) 2.141(3)
Ag(2)–O(21) 3.012(7)
Ag(2)–O(210) 3.234(14)
Bond angles (°)
N(1A)–Ag(1)–N(4B) 168.30(12)
N(1A)–Ag(1)–Ag(2) 103.65(8)
N(4B)–Ag(1)–Ag(2) 68.35(8)
N(1A)–Ag(1)–O(11) 82.69(13)
N(4B)–Ag(1)–O(11) 105.55(13)
Ag(2)–Ag(1)–O(11) 173.58(10)
N(1A)–Ag(1)–O(13) 109.69(14)
N(4B)–Ag(1)–O(13) 81.74(14)
Ag(2)–Ag(1)–O(13) 133.53(10)
O(11)–Ag(1)–O(13) 41.35(13)
N(1B)–Ag(2)–N(4A) 172.79(12)
N(1B)–Ag(2)–O(21) 92.53(19)
N(4A)–Ag(2)–O(21) 93.9(2)
N(1B)–Ag(2)–Ag(1) 99.97(8)
N(4A)–Ag(2)–Ag(1) 74.23(8)
O(21)–Ag(2)–Ag(1) 164.88(17)
N(1B)–Ag(2)–O(210) 76.8(2)
N(4A)–Ag(2)–O(210) 109.3(2)
Ag(1)–Ag(2)–O(210) 174.4(2)
Fig. 5. Packing diag am o [Ag2(2-BIM(Bz)OH)2](ClO4)2E OH.
1252 S. Abuskhuna e al. / Polyhed on 23 (2004) 1249–1255
33.07. Found: C, 61.26; H, 5.47; N, 32.76%. 1H
NMR(DMSO-d6): 7.17 (2H, d, J¼1:3 Hz), 6.8 (2H, d,
J¼1:3 Hz), 4.3 (4H, , J¼6:7 Hz), 4.2 (2H, s), 3.0 (4H,
, J¼6:7 Hz) ppm. 13C NMR(DMSO-d6): 143.6, 127.3,
120.8, 118.8, 25.4, 19.2 ppm. IR: 3125, 2932, 2264, 1485,
1447, 1383, 1287, 1166, 1134, 1089, 926, 722, 743, 705
cm1. Mass spec.: m=z: 254 (Mþ, 4%), 200 (4), 173 (8),
161 (6), 148 (10), 134 (11), 120 (14), 107 (14), 94 (28), 82
(84), 66 (20), 54 (100).
3.2. 2-BIM(BzCl)
2,6-Dichlo obenzyl chlo ide (0.53 g, 2.7 mmol) was
added o a s i ed mix u e o 2-BIM (0.2 g, 1.3 mmol)
and sodium hyd ide (0.06 g, 2.5 mmol) in d y DMF (15
cm3). The mix u e was s i ed o e nigh a oom em-
pe a u e and he sol en emo ed unde educed p es-
su e. Wa e (20 cm3) was added and he p oduc
ex ac ed wi h dichlo ome hane, and he dichlo ome-
hane solu ion was hen d ied o e magnesium sulpha e.
A e fil a ion he sol en was emo ed unde educed
p essu e. The esul ing b own oily esidue was diges ed
in cyclohexane and he whi e p oduc p ecipi a ed upon
cooling. Yield: 0.34 g (54%). Mp 93 °C. Anal. Calc. C,
54.10; H, 3.43; N, 12.02. Found: C, 54.09; H, 3.58; N,
11.73%. 1H NMR (CDCl3): 7.4 (2H, d, J¼2 Hz), 7.1
(2H, dd, J¼8:3 Hz), 6.9 (2H, d, J¼1:3 Hz), 6.7 (2H, d,
J¼1:3 Hz), 6.5 (2H, d, J¼8:3 Hz), 5.2 (4H, s), 4.2
(2H, s). 13C NMR (CDCl3): 143, 134.5, 133.6, 132.7,
129.5, 129.1, 128.1, 127.5, 120.5, 47, 27 ppm. IR: 2945,
1593, 1485, 1447, 1389, 1274, 1121, 1057, 849, 733, 682
cm1. Mass spec.: m=z: 466 (Mþ, 16%), 429 (4), 305 (26),
269 (8), 205 (8), 159 (100), 147 (8), 123 (16), 99 (6), 89
(16), 81 (38), 63 (10).
3.3. [Ag2(2-BIM)2](ClO4)2
Sil e pe chlo a e (0.70 g, 3.37 mmol) was added o a
s i ed solu ion o 2-BIM (0.5 g, 3.37 mmol) in me hanol
(15 cm3) and he mix u e s i ed o 1 h a oom em-
pe a u e. The p ecipi a ed whi e was fil e ed off, washed
wi h me hanol and ai -d ied. Yield: 1.00 g (83%). Anal.
Calc. C, 23.64; H, 2.25; N, 15.76. Found: C, 23.58; H,
2.13; N, 15.78%. IR: 3344, 3151, 1293, 1095, 759, 624
cm1.1H NMR (ppm DMSO): 6.8 (8H, s), 4 (4H, s).
The complex was soluble in ho ace oni ile and DMSO,
and c ys als sui able o X- ay analysis we e ob ained by
ec ys allising om ace oni ile.
3.4. [Ag2(2-BIM(Bz)OH)2](ClO4)2E OH
This whi e complex was p epa ed and ec ys allised in
a simila way o [Ag2(2-BIM)2](ClO4)2using sil e pe -
chlo a e (0.06 g, 0.17 mmol) and 2-BIM(Bz)OH (0.1 g,
0.29 mmol). Yield: 0.11 g (68%). Anal. Calc. C, 43.87; H,
3.48; N, 9.70. Found: C, 44.21; H, 3.45; N, 9.69%. IR:
2485, 3138, 2971, 1497, 1459, 1287, 1102, 827, 717, 624
cm1.1H NMR (ppm DMSO): 5.2 (8H, dd), 6.4 (2H, d),
7.1 (8H, s), 7.35 (20H, m). The complex was soluble in
ho ace oni ile, ho ace one and DMSO.
3.5. [Ag2
{
2-BIM(Me)
}
2](ClO4)2
To a solu ion o sil e pe chlo a e (0.10 g, 0.48 mmol)
in me hanol (3 cm3) was added a solu ion o 2-BIM(Me)
(0.10 g, 0.56 mmol) in me hanol (3 cm3). A whi e p e-
cipi a e o med immedia ely and he eac ion mix u e
was s i ed o 20 min a oom empe a u e. The whi e
p oduc was fil e ed off, washed wi h me hanol and hen
d ied in ai . Yield: 0.13 g (62%). Anal. Calc. C, 28.10; H,
3.13; N, 14.60. Found: C, 27.5; H, 3.00; N, 14.13%. IR:
3485, 3138, 2971, 1497, 1414, 1293, 1102, 772, 627 cm1.
1H NMR (ppm DMSO): 3.5 (12H, s), 4.36 (4H, s), 6.8
(4H, s), 7.2 (4H, s). The complex was soluble in ho
ace oni ile, ho ace one and DMSO.
3.6. [Ag2
{
2-BIM(CN)
}
2](ClO4)2
This whi e complex was p epa ed in a simila way o
[Ag2{2-BIM(Me)}2](ClO4)2using sil e pe chlo a e
(0.10 g, 0.48 mmol) and 2-BIM(CN) (0.20 g, 0.78 mmol).
Yield: 0.32 g (89%). Anal. Calc. C, 33.81; H, 3.03; N,
18.20. Found: C, 33.46; H, 2.92; N, 18.20%. IR: 3511,
3138, 2984, 2264, 1497, 1427, 1287, 1102, 756, 627 cm1.
1H NMR (ppm DMSO): 7.3 (4H, s), 6.8 (4H, s), 4.4 (4H,
s), 4.2 (8H, ), 2.9 (8H, ). The complex was soluble in
ho ace oni ile, ho ace one and DMSO.
3.7. [Ag2
{
2-BIM(BzCl)
}
2](ClO4)2
This whi e complex was p epa ed in a simila way o
[Ag2{2-BIM(Me)}2](ClO4)2using sil e pe chlo a e
(0.08 g, 0.38 mmol) in 3 ml me hanol was added o 2-
BIM(BzCl) (0.20 g, 0.43 mmol). Yield: 0.16 g (57%).
Anal. Calc. C, 37.43; H, 2.37; N, 8.31. Found: C, 37.03;
H, 2.41; N, 8.04%. IR: 3511, 3138, 1593, 1491, 1395,
1274, 1102, 836, 749, 628 cm1.1H NMR (ppm
DMSO): 7.9 (4H, d), 7.56 (4H, dd), 7.5 (4H, d),7.25 (4H,
d) 6.8 (4H, d), 5.5 (8H, s), 4.8 (4H, s). The complex was
soluble in ho ace oni ile, ho ace one and DMSO.
3.8. An i-Candida es ing
Candida albicans ATCC 10231 was ob ained om he
Ame ican Type Cul u e Collec ion (Manasas, VA,
USA). Cul u es we e g own on Sabou aud dex ose
aga (SDA) pla es a 37 °C and main ained a 4 °C o
sho - e m s o age. Minimum inhibi o y concen a ions
(MICs) we e de e mined as ollows. RPMI-1640 b o h
medium was used o he an i-Candida suscep ibili y
es ing. RPMI (5.15 g) was dissol ed in cold dis illed
wa e (425 cm3) in a 1-l Du an bo le and he pH
S. Abuskhuna e al. / Polyhed on 23 (2004) 1249–1255 1253

adjus ed o 4.0 using a ew d ops o HCl (ca. 2 M). The
esul ing solu ion was au ocla ed and hen allowed o
cool o app oxima ely 50 °C. Mo pholinep opanesul -
onic acid (MOPS) (17.3 g) and
LL
-glu ama e (0.15 g) we e
dissol ed oge he wi h s i ing in dis illed wa e (50
cm3) and he esul ing solu ion fil e s e ilized. The
MOPS and
LL
-glu ama e solu ion was added o he wa m
RPMI and he pH o he mix u e adjus ed o 7.0 using
s e ile NaOH (6 M). P io o MIC es ing, cells we e
g own on SDA a 37 °C o 24 h. Cell suspensions we e
p epa ed in s e ile phospha e buffe ed saline (PBS, pH
7.2) and cells we e coun ed mic oscopically ollowing
dilu ion wi h PBS. A mic o i e pla e was inocula ed
wi h cells a a densi y o 5 105cells cm3. Tes sus-
pensions (in wa e ) and solu ions (in aqueous DMSO) o
he sil e complexes we e each p epa ed as ollows.
Suspensions in wa e : he complex (0.02 g) was sus-
pended in dis illed wa e (10 cm3) o yield a s ock sus-
pension o concen a ion 2000 lgcm
3. Doubling
dilu ions o he s ock suspension we e made o yield a
se ies o es suspensions anging in complex concen-
a ion om 20 o 1.25 lgcm
3.Solu ions in DMSO: he
complex (0.02 g) was dissol ed in DMSO (10 cm3) o
yield a s ock solu ion o concen a ion 2000 lgcm
3.
Doubling dilu ions o he s ock solu ion we e made
using dis illed wa e o yield a se ies o es solu ions
anging in complex concen a ion om 20 o 1.25
lgcm
3. The DMSO concen a ion (% / ) in he es
solu ions anged om 1.0% o 0.06% (no e ha a 2%
DMSO aqueous solu ion, wi hou added complex, does
no inhibi he g ow h o he mic oo ganism whe eas a
3% DMSO aqueous solu ion will a es cell g ow h o-
ally). Fo he aqueous es suspensions and he aque-
ous-DMSO es solu ions he complex/cell mix u es
we e incuba ed a 37 °C o 24 h wi h con inuous
shaking and he assays we e pe o med in iplica e.
Pla es we e ead using a Labsys ems iEMS Reade MF
(abso bance a k¼540 nm) and da a we e s a is ically
analysed.
3.9. X- ay c ys allog aphy
All o he da a we e collec ed a 150 K on a B uke
SMART 1000 diff ac ome e using Mo Ka adia ion
(k¼0:71073

A). The s uc u es we e sol ed by di ec
me hods and efined by ull-ma ix leas -squa es on F2
using all he eflec ions. One o he p echlo a e anions in
[Ag2(2-BIM(Bz)OH)2](ClO4)2E OH is diso de ed and
was modeled wi h wo al e na i e se s o oxygen a om
posi ions (50% occupancy each). The e hanol sol a e is
also diso de ed and was modeled as 50% occupancy o
wo al e na i e posi ions. All non-hyd ogen a oms we e
efined wi h aniso opic a omic displacemen pa ame-
e s and hyd ogen a oms bonded o ca bon we e in-
se ed a calcula ed posi ions. Hyd ogen a oms bonded
o ni ogen ([Ag2(2-BIM)2](ClO4)2) o he ligand alco-
hol g oup ([Ag2(2-BIM(Bz)OH)2](ClO4)2E OH) we e
loca ed om diffe ence maps and no u he efined;
hose bonded o he diso de ed oxygen o he e hanol
sol a e in [Ag2(2-BIM(Bz)OH)2](ClO4)2E OH we e
no included in he model. All p og ammes used in he
s uc u e solu ion and efinemen a e included in he
SHELXTLSHELXTL
package [18] and da a collec ion and efine-
men de ails a e summa ised in Table 3.
Table 3
X- ay c ys allog aphic da a. C ys al da a and s uc u e efinemen o [Ag2(2-BIM)2](ClO4)2and [Ag2(2-BIM(Bz)OH)2](ClO4)2E OH
Iden ifica ion code [Ag2(2-BIM)2](ClO4)2[Ag2(2-BIM(Bz)OH)2](ClO4)2E OH
Empi ical o mula C14H16Ag2Cl2N8O8C44H46Ag2Cl2N8O11
Fo mula weigh 710.99 1149.53
C ys al sys em iclinic iclinic
Space g oup P

1P

1
a(

A) 7.8149(10) 10.9636(7)
b(

A) 8.9902(11) 14.7743(9)
c(

A) 9.2559(11) 16.0180(10)
a(°) 108.046(2) 114.3870(10)
b(°) 98.283(2) 98.2900(10)
c(°) 114.763(2) 95.8410(10)
Volume (

A3) 532.47(11) 2300.6(2)
Z12
F(0 0 0) 348 1164
C ys al size (mm) 0.16 0.25 0.31 0.37 0.25 0.14
h ange o da a collec ion (°) 2.44–28.65 1.54–25.00
Reflec ions collec ed 4544 16522
Independen eflec ions [Rðin Þ] 2396 [0.0186] 8050 [0.0159]
Abso p ion co ec ion mul iscan mul iscan
Maximum and minimum ansmission 1.0000 and 0.8116 1.000000 and 0.912980
Da a/ es ain s/pa ame e s 2396/0/154 8050/98/667
R1,wR2[I>2 ðIÞ] 0.0198, 0.0526 0.0356, 0.0877
R1,wR2(all da a) 0.0204, 0.0530 0.0455, 0.0942
1254 S. Abuskhuna e al. / Polyhed on 23 (2004) 1249–1255
4. Supplemen a y da a
X- ay supplemen a y da a o [Ag2(2-BIM)2](ClO4)2
and [Ag2(2-BIM(Bz)OH)2](ClO4)2E OH a e a ailable
om he Camb idge C ys allog aphic Da a Cen e, 12
Union Road, Camb idge CB2 1EZ, England ( ax: +44-
1223-336033; E-mail: deposi @ccdc.cam.ac.uk o www:
h p://www.ccdc.cam.ac.uk), on eques quo ing he de-
posi ion numbe s CCDC 219908 and CCDC 219909,
espec i ely.
Acknowledgemen s
S. Abuskhuna acknowledges financial suppo om
he Libyan Highe Educa ion Depa men .
Re e ences
[1] B. Coyle, K. Ka anagh, M. McCann, M. De e eux, M. Ge agh y,
BioMe als 16 (2003) 321.
[2] B. Coyle, P. Kinsella, M. McCann, M. De e eux, R. O’Conno ,
M. Clynes, K. Ka anagh, Toxicology in Vi o 18 (2004) 63.
[3] M. Ge agh y, J.F. C onin, M. De e eux, M. McCann, BioMe als
13 (2000) 1.
[4] M. McCann, B. Coyle, J. B iody, F. Bass, N. O’Go man, M.
De e eux, K. Ka anagh, V. McKee, Polyhed on 22 (2003)
1595.
[5] M. McCann, B. Coyle, S. McKay, P. McCo mack, K. Ka anagh,
M. De e eux, V. McKee, P. Kinsella, R. O’Conno , M. Clynes,
Biome als (2004), in p ess.
[6] C. Place, J.-L. Zimme mann, E. Mulliez, G. Guillo , C. Bois, J.-C.
Cho a d, Ino g. Chem. 37 (1998) 4030.
[7] S. Elgafi, B.A. Messe le, T.W. Hambley, P. Tu ne , J. Chem. Soc.
Dal on T ans. (1997) 2341.
[8] R. Bhalla, M. Helliwell, C.D. Ga ne , J. Chem. Soc., Chem.
Commun. (1996) 921.
[9] X.-M. Chen, Z.-T. Xu, T.C.W. Mak, Polyhed on 14 (1995) 319.
[10] M.J. Bloemink, H. Engelking, S. Ka en zopoulos, B. K ebs, J.
Reedijk, Ino g. Chem. 35 (1996) 619.
[11] M. G ehl, B. K ebs, Ino g. Chem. 33 (1994) 3877.
[12] S. Abuskhuna, J. B iody, M. McCann, M. De e eux, K.
Ka anagh, V. McKee, Polyhed on, o be published.
[13] P. Majumda , K.K. Kama , A. Cas i~
nei as, S. Goswami, J. Chem.
Soc., Chem. Commun. (2001) 1292.
[14] M. Joseph, T. Leigh, M.L. Swain, Syn hesis 7 (1977) 459.
[15] R.S. B own, R.G. Clewely, J. O g. Chem. 52 (1987) 1216.
[16] B.P. Can well, Ph.D. Thesis, NUI Maynoo h, 1992.
[17] A.M. Roe, J. Chem. Soc. (1963) 2195.
[18] G.M. Sheld ick,
SHELXTLSHELXTL
e sion 6.12, B uke AXS, Madison,
WI, 2001.
S. Abuskhuna e al. / Polyhed on 23 (2004) 1249–1255 1255