Zinc complexes with 1,2,4-triazole functionalized amino acid derivatives: Synthesis, structure and β-lactamase assay

Article abstract of DOI:10.1016/j.ica.2010.12.017

Coordinating abilities of 4R-1,2,4-triazole derivatives (R = glycine ethyl ester (L1), glycine (L2), diethylamino malonate (L3), methionine (L4) and diethyl aminomethylphosphonate (L5)) towards Zn^II ions have been studied in solution, in solid state and versus three zinc-β-lactamases. The crystal structure of [Zn₃(L4)₆(H₂O) ₆] (6) is described; it is the first crystal structure involving a 1,2,4-triazole functionalized methionine. It forms a trinuclear complex with central zinc octahedrally coordinated by only L4, whereas terminal zinc ions coordination sphere is completed by three water molecules. L4 exhibits a dual functionality of a bridging bidentate ligand as well as an anion. A dense hydrogen bonding network connects these trinuclear entity into a 3D supramolecular network. The Zn^II ions in 6 are held at equidistance (3.848 A?) which coincidently matches with the corresponding Zn?Zn distance in the binuclear zinc enzyme from Bacillus cereus (3.848 and 4.365 A?). Among L1-L5 screened for β-lactamase assay, L4 shows modest inhibition for BcII enzyme.

Full text of DOI:10.1016/j.ica.2010.12.017

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Inorganica Chimica Acta 368 (2011) 21–28
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Zinc complexes with 1,2,4-triazole functionalized amino acid derivatives: Synthesis,
structure and b-lactamase assay
Anil D. Naik a, Joséphine Beck a, Marinela M. Dîrtu a, Carine Bebrone b, Bernard Tinant a, Koen Robeyns a,
Jacqueline Marchand-Brynaert a, Yann Garcia a,
⇑
a Institute of Condensed Matter and Nanosciences, Université Catholique de Louvain, Place L. Pasteur 1, 1348 Louvain-la-Neuve, Belgium
b Centre d’Ingénierie des Protéines, Université de Liège, B6-Sart Tilman, 4000 Liège, Belgium
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 August 2010
Received in revised form 1 December 2010
Accepted 9 December 2010
Available online 23 December 2010
Coordinating abilities of 4R-1,2,4-triazole derivatives (R = glycine ethyl ester (L1), glycine (L2), diethyl-
amino malonate (L3), methionine (L4) and diethyl aminomethylphosphonate (L5)) towards ZnII ions have
been studied in solution, in solid state and versus three zinc-b-lactamases. The crystal structure of
[Zn3(L4)6(H2O)6] (6) is described; it is the first crystal structure involving a 1,2,4-triazole functionalized
methionine. It forms a trinuclear complex with central zinc octahedrally coordinated by only L4, whereas
terminal zinc ions coordination sphere is completed by three water molecules. L4 exhibits a dual func-
tionality of a bridging bidentate ligand as well as an anion. A dense hydrogen bonding network connects
these trinuclear entity into a 3D supramolecular network. The ZnII ions in 6 are held at equidistance
(3.848 Å) which coincidently matches with the corresponding Znꢀ ꢀ ꢀZn distance in the binuclear zinc
enzyme from Bacillus cereus (3.848 and 4.365 Å). Among L1–L5 screened for b-lactamase assay, L4 shows
modest inhibition for BcII enzyme.
Keywords:
1,2,4-Triazole
Zinc complexes
Amino acids
Trinuclear complex
b-Lactamase
Ó 2010 Elsevier B.V. All rights reserved.
1. Introduction
N-benzesulfonyl-L-glutamic acid [8d], and a chiral metal organic
framework (MOF) from condensation product of glutamate moie-
ties with xylene [4].
Amino acids are the building blocks of proteins and the central
trunk from which many diverse applied fields have branched out
[1]. Not only amino-acids but also their derivatives have surfaced
into biochemistry, pharmacology, peptide station, bio-mimics,
enantioselective catalysis and separation, non-linear optics and
materials science [1–3]. Advantage of these molecules is their nat-
ural miscellaneous framework with rich functional groups, which
is amenable to copious derivatization. The diverse topology they
adopt steering the crystal packing in molecular architectures
through extended supramolecular interactions is intriguing [4–8].
Structure and reactivity of different amino acids in their natural
or derivatized form were extensively studied; some elegant exam-
ples include proline [7a], glycine [7a], alanine [7b], aspartic acid
[7c], phenyl alanine [7d], histidine [7e], methionine [7f–i] and
typtophan [7j]. Diverse applications are quoted such as metal-
peptide frameworks constructed from an oligovaline family [8a],
a chiral metal Cu(II) cluster from dipeptidic N,N0-terephthaloyl-
bis(S-aminocarboxylato) ligand [8b], a 2D Cu(II) network built
We recently introduced a simplified transamination reaction for
converting the amine functional group of glycine into a 1,2,4-tria-
zole [9]. Our interest in amino acid derivatization was fuelled by
promising results shown by 1,2,4-triazole-carboxylate derivatives
in synthetic chemistry [9], spin crossover phenomenon [10] and
nanoporous MOFs [11]. Applications envisioned in these fields lar-
gely depend on molecular conformations these precursors adopt
during the self-assembly process which directs structure-proper-
ties relationships. Here we introduce a set of natural and non-
natural amino acids selected for their functional group diversity
to functionalize into 1,2,4-triazoles (Scheme 1). Such groups
(N-heterocycle, acid, carboxylate, phosphate and thiomethyl) could
be potential ligands of MII cations, in particular ZnII is found as
co-factor in several metallo-proteases.
Thus in continuation of our transamination strategy [9],
exemplified with ligands L1 and L2, we introduce new tailored
4R-1,2,4-triazoles from amino-acid and amino-acid esters, namely
diethyl aminomalonate (L3), methionine (L4) and diethyl amin-
omethylphosphonate (L5) (Scheme 1). Their coordinating abilities
towards ZnII along with ligands from glycine ethyl ester (L1) and
glycine (L2) [9] have been studied in solution, in solid state and
versus three zinc-b-lactamases.
from
L-tryptophanato ligand [8c], coordination polymers of
⇑
Corresponding author. Fax: +32 10 472330.
E-mail address: yann.garcia@uclouvain.be (Y. Garcia).
0020-1693/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2010.12.017

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A.D. Naik et al. / Inorganica Chimica Acta 368 (2011) 21–28
Scheme 1. 4-R-1,2,4-Triazoles derived from aminoacids.
10 mM in DMSO solution before dilution with appropriate buffers.
2. Experimental
Buffers were, respectively, 10 mM Hepes pH 7.5 for BcII, 15 mM
Cacodylate pH 6.5 for CphA and 20 mM Hepes pH 7.0 for L1. The
three buffers were prepared with Milli-Q water and ZnII residual
2.1. Chemicals
concentration was below 0.4 lM. Tests verified that the low con-
All reagents and solvents were used as received from commer-
cial sources: benzene, N,N-dimethylformamide, (Sigma–Aldrich),
glycine ethyl ester hydrochloride, diethyl aminomalonate hydro-
chloride, p-toluene sulfonic acid, thionyl chloride, (Acros), DL-
methionine (Janssen chimica), aq. hydrazine hydrate (Aldrich),
Zn(OAc)2ꢀ2H2O (UCB), and ZnCl2 (Fluka).
centration of DMSO present had no inhibition effect: the rate re-
mained the same upon addition of 1% DMSO. BcII, CphA, and L1
enzymes were used at concentrations of 8, 1.6 and 1.4 nM, respec-
tively. The enzyme and the 100
lM inhibitor were pre-incubated
30 min in a volume of 490 mL at room temperature. Then, 10
l
L
of 5 mM imipenem were added and the hydrolysis of imipenem
was monitored by following the variation in absorbance at
300 nm, using an UvikonXL spectrophotometer connected to a
computer via a RS232 serial interface. The experiments were per-
formed at 30 °C and initial rate conditions were used to study
the inhibition with imipenem. The assays were made in triplicate;
the error was less than 5%.
2.2. Instrumentation
1H and 13C NMR spectra were recorded at 300 MHz and 75 MHz,
respectively, on a Bruker AC300 instrument. The residual solvent
peak was used as internal reference. FTIR spectra were recorded
on a Bio-Rad FTS 135 spectrometer using KBr discs. Mass spectral
data were obtained on Thermo Finnigan LCQ Ion trap spectrometer
(APCI mode). HRMS were carried out on a Micromass Q TOF 2 spec-
trometer in ESI mode, detecting positive ions. CHN analyses were
performed at the University College London (UK). TGA-DTA
analyses were performed in air at a heating rate of 10 K/min
(298–1173 K) using an Universal V2.5H TA instrument. Zn% was
determined from ZnO residue obtained from TGA analysis of all
freshly prepared zinc complexes that were preliminary dried in
air. Powder X-ray diffraction patterns were recorded on a Siemens
3. Synthesis
3.1. Synthesis of ligands
N,N-dimethylformamide azine dihydrochloride (a) and its free
base (b) are obtained following Refs. [15,16] (Scheme 2); b was
recrystallised from benzene with charcoal as colourless flakes
and used in following transamination reactions (Caution: all oper-
ations concerned with benzene, which is a possible carcinogen,
should be carried out in an efficient fume hood). Diethyl amin-
omethylphosphonate was prepared by the reported methods
[17,18]. Synthesis of ethyl 4H-1,2,4-triazol-4-yl-acetate (L1), 4H-
1,2,4-triazol-4-yl acetic acid (L2) were carried out following [9].
D5000 counter diffractometer working with
a Ka radiation
(1.5418 Å) at 293 K. Melting points were determined with an oil
bath 3937-S Buchi device. Column chromatography was performed
on silica gel 60 (63–200 mesh, Merck). Scanning electron micros-
copy (SEM) coupled with EDX was performed with a Gemini Digital
Scanning Microscope 982 with 1 kV accelerating voltage using an
aluminium sample holder. Solid state emission spectra were re-
corded on Fluorolog-3 (Jobin-Yvon-Spex) spectrometer. Activity
test were monitored by using an UvikonXL spectrophotometer
connected to a computer via a RS232 serial interface. Diffuse reflec-
tance spectra were recorded with a CARY 5E spectrophotometer
using Teflon as a reference.
3.1.1. Diethyl 4H-1,2,4-triazol-4-yl malonate (L3)
The reaction was carried out in a dry round-bottomed flask
fitted with a reflux condenser. Solid b (500 mg, 3.5 mmol) was
added under stirring to a suspension of diethyl aminomalonate
hydrochloride (745 mg, 3.5 mmol) in benzene (30 mL) at
approximately 60 °C. The mixture was refluxed for 24 h with
vigorous stirring. The reaction can be monitored by running thin
layer chromatography at interval of time. Finally, solvent was
removed under vacuum and chromatographic purification (SiO2,
CH2Cl2 ? 5% isopropanol in CH2Cl2) afforded a yellow oil, which
upon repeated crystallization from ether-methanol mixture pro-
vided a white hygroscopic solid (0.45 g, 56%), m.p 63 °C. Rf 0.3
(5% isopropanol in CH2Cl2). FTIR (KBr, cmꢁ1): 3126(w), 1743(vs),
1523(m), 1303(vs), 1193(vs), 1020(vs), 869(s). 1H NMR
2.3. b-Lactamase assay
L1–L5 were screened for inhibition against three representative
metallo-b-lactamases, namely BcII from Bacillus cereus [12], CphA
from Aeromonas hydrophila [13] and L1 from Stenotrophomoncas
maltophilia [14] representing B1, B2 and B3 sub-classes. L1, L2,
L3, and L5 were prepared as 10 mM in water solutions and L4 as

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A.D. Naik et al. / Inorganica Chimica Acta 368 (2011) 21–28
23
Scheme 2. Synthetic protocol used for L3.
(300 MHz, CDCl3, 298 K): d = 8.6 (s, 2H), 5.86 (s, 1H), 4.28–4.36 (m,
4H), 1.31 (t, 6H). 13C NMR (75 MHz, CDCl3, 298 K): d = 163.5, 142.8,
63.9, 60.77,14.01, MS: m/z = 228.14 (M+H+). Anal. Calc. for
C9H13N3O4ꢀH2O (245.10): C, 44.06; H, 6.17; N, 17.14. Found: C,
44.56; H, 5.75; N, 17.21%. Refluxing L3 with 6 N HCl leads to hydro-
lysis followed by decarboxylation. Analysis on the product con-
firms formation of L2 (Lit. [9], m.p 161 °C).
1748(s), 1595 (br, s), 1385(s), 1076(m), 1023(m), 677(s), 635(m).
1H NMR (300 MHz, CD3OD, 298 K): d = 8.62 (s, 4H), 5.1 (s, 4H).
3.61 (q, 4H, J = 7.05 Hz), 1.18 (t, 6H, J = 7.05), 2.05 (s, 6H, CH3 of ace-
tate). 13C NMR (75 MHz, CD3OD, 298 K): d = 181.2, 169.8, 147.3,
59.2, 48.07, 23.1, 19.2. ESI-MS: cluster of peaks at m/z = 493 corre-
sponds to [M+H+] (calc. 492.09).
3.2.2. [Zn(L1)2Cl2]ꢀ3MeOH (2)
Reaction of ZnCl2 (22 mg, 0.16 mmol) in MeOH (5 mL) with L1
(50 mg, 0.32 mmol) in MeOH (5 mL) resulted in the isolation of a
white precipitate (2) which was dried in air. Yield 35 mg, (50%).
FTIR (KBr, cmꢁ1): 3130(m), 1747(vs), 1556(m), 1247(s), 1224(s),
1029(m), 630(m). 1H NMR (300 MHz, d6-DMSO, 298 K): d = 8.56
(s, 4H), 5.09 (s, 4H). 4.20 (q, 4H, J = 7.11 Hz), 1.25 (t, 6H, J = 7.11).
13C NMR (75 MHz, d6-DMSO 298 K): d = 168, 144.8, 62.2, 46.26,
14.77. ESI-MS: cluster of peaks at m/z = 444.78, ([M+H+] (calc.
444.0). The sample begins to loose solvent molecule over a period
of time. Anal. Calc. for C12H18N6O4ZnCl2ꢀMeOH: C, 32.77; H, 4.66; N,
17.65; Zn, 12.05. Found: C, 31.86; H, 3.61; N, 17.89; Zn, 11.5%. Deg-
radation temperature by DTA (onset point): 240(1) °C.
3.1.2. 4-(methylthio)-2-(4H-1,2,4-triazol-4-yl)Butanoic acid (L4)
DL-methionine (100 mg, 0.67 mmol) was suspended in benzene
(20 mL) and warmed to 70 °C. Solid azine dihydrochloride a
(144 mg, 0.67 mmol) was added with stirring and the mixture fur-
ther refluxed for 24 h with vigorous stirring. A pale yellow viscous
mass was obtained. Solvent was evaporated under reduced pres-
sure and the residue dissolved in dry MeOH (4 mL). Insoluble res-
idue was filtered off, and solvent evaporated to yield a pale yellow
viscous solid. The residue was redissolved in CHCl3 (20 mL), dried
over sodium sulfate and filtered. The filtrate was cooled in refriger-
ator overnight. Colourless needles obtained were filtered, dried and
stored in desiccator. m.p 94 °C. Yield 0.1 g (75%). FTIR (KBr, cmꢁ1):
3417(br), 1712(s), 1635(s), 1467(m), 1188(m), 1022(s), 887(m). 1H
NMR (300 MHz, DMSO-d6, 298 K): d = 8.64 (s, 2H), 5.28 (t, 1H,
J = 7.2 Hz), 2.27–2.40 (m, 4H), 2.06 (s, 3H). 13C NMR (75 MHz,
DMSO-d6, 298 K): d = 172.2, 145, 58.7, 32.8, 31.2, 15.3. APCI MS
m/z = 202.04 (M+1). Anal. Calc. for C7H11N3O2S (201.25): C, 41.78;
H, 5.51; N, 20.88. Found: C, 41.68; H, 5.46; N, 21.48%.
3.2.3. [Zn(L2)2]ꢀCH3OH (3)
Zn(OAc)2ꢀ2H2O (43.2 mg, 0.196 mmol) dissolved in MeOH
(2 mL), was added with stirring to a methanolic (2 mL) solution
of L2 (50 mg, 0.39 mmol) at r.t. The mixture was stirred for
15 min and the white precipitate obtained was filtered, washed
with MeOH (1 mL) and dried in air (3). Yield 51 mg (80%). FTIR
(KBr, cmꢁ1): 3089(m), 1743(m), 1735(m), 1641(s), 1560(m),
1392(s), 1230(m), 1039(m), 919(w), 790(m), 698(m), 634(m). 1H
NMR (300 MHz, D2O, 298 K): d = 10.58 (s, 4H), 6.8 (s, 4H). 13C
NMR (75 MHz, D2O, 298 K): d = 175.5, 147.7, 51. Anal. Calc. for
C8H8N6O4Zn (315.98): C, 30.38; H, 2.55; N, 26.59; Zn, 18.37. Found:
C, 29.88; H, 3.76; N, 26.13l Zn, 18.90%.
3.1.3. Diethyl 4H-1,2,4-triazol-4-yl methylphosphonate (L5)
The same synthetic procedure used for L3 (amine 50 mg,
0.29 mmol; 38.6 mg of b, 0.27 mmol) was followed but with a cat-
alytic amount of p-toluene sulfonic acid. The yellow oil obtained
after solvent evaporation was dissolved in CH2Cl2 and washed with
a saturated NaCl solution that was basified with sodium carbonate
(pH 8–9). The organic layer was dried over sodium sulfate, solvent
removed under vacuum and the yellow oil thus obtained was dried
under vacuum. FTIR (film, cmꢁ1): 2983(m), 1643(br, m), 1548(m),
1444(m), 1392(m), 1230(s), 1163(m), 1010(s), 970(s), 794(m),
605(s). 1H NMR (300 MHz, CDCl3, 298 K): d = 8.23 (s, 2H), 4.32 (d,
2H, JP,H = 12.9 Hz), 4.05–4.15 (m, 4H), 1.27 (t, 6H). 13C NMR
(75 MHz, CDCl3, 298 K): d = 143.3, 63.68 (d, JC,P = 7 Hz), 41.18 (d,
JC,P = 158 Hz), 16.5. APCI MS: m/z = 219.71 (M+H+). HRMS calcd.
for C7H15N3O3P: 220.0851. Found: 220.0847.
3.2.4. [Zn(L3)2(Cl)2] (4)
L3 (50 mg, 0.22 mmol) was dissolved in MeOH (2 mL) and to this
was added ZnCl2 (15 mg, 0.11 mmol) in MeOH (2 mL). Reaction was
completed within 30 min and concentration of reaction mixture
yielded a yellow oil (4). Yield 65 mg, (100%). FTIR (film, cmꢁ1):
1742(br, s), 1698(s), 1544(m), 1371(m), 1307(s), 1020(s), 891(m),
639(s). 1H NMR (300 MHz, CDCl3, 298 K): d = 8.81 (s, 2H), 6.1(s,
1H), 4.21–4.28 (q, 4H), 1.33 (t, 6H, J = 7.11 Hz). 13C (75 MHz, CDCl3,
298 K): d = 163.4, 144.9, 64.2, 61.4, 14.0. ESI MS shows packet of
peaks centred around 552 corresponding to [Zn + 2L3 + Cl]+. Peak
found at 781 was calculated as [Zn + 3L3 + Cl]+.
3.2. Synthesis of complexes
3.2.1. [Zn(L1)2(OAc)2] (1)
A
methanolic solution (2 mL) of Zn(OAc)2ꢀ2H2O (35.4 mg,
3.2.5. [Zn3(L4)6(MeOH)6] (5) and [Zn3(L4)6(H2O)6] (6)
0.16 mmol) was added to a methanolic (2 mL) solution of L1
(50 mg, 0.32 mmol). The mixture was stirred slowly at r.t. and
the progress of the reaction monitored by 1H NMR at an interval
of 0.5 h for 2 h. After reaction completion, solvent evaporation gave
a colourless oil (1). Yield 78 mg (100%) FTIR (cmꢁ1): 3126(w),
Zn(OAc)2ꢀ2H2O (54 mg, 0.49 mmol) in MeOH (2 mL) was added
with stirring to a methanolic solution of L4 (100 mg, 0.98 mmol) at
r.t. resulting immediately in a pale yellow precipitate. The mixture
was stirred for 15 min, filtered, washed with MeOH (1 mL) and
dried in air to afford a white precipitate (5). Yield 150 mg (65%).

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A.D. Naik et al. / Inorganica Chimica Acta 368 (2011) 21–28
FTIR (KBr, cmꢁ1): 3485(br), 1647(s), 1382(m), 1197(m), 1078(m),
885(m), 667(m). 1H NMR (300 MHz, DMSO-d6, 298 K): d = 8.67 (s,
4H), 5.01–5.05 (m, 2H), 2.32–2.41 (m, 8H), 2.05 (s, 6H). 13C NMR
(75 MHz, DMSO-d6, 298 K): d = 173.3, 144.5, 59.4, 33, 30.6, 15.4.
Diffuse reflectance spectra (kmax, nm), 270, 325 nm. Anal. Calc. for
ther with a nor b under experimental conditions of variation of sol-
vents and catalyst (benzene/toluene; with/without catalyst). All
these hygroscopic molecules (L1–L5) are soluble in water, MeOH,
DMF and DMSO.
Coordinating affinities of these ligands towards ZnII were first
studied in solution. Complexes were synthesized either with ZnCl2
or Zn(OAc)2 in MeOH at r.t. and the reaction was followed by 1H
NMR. Complexes formed with L1, L3 and L5 were quite sensitive
to solvent medium, temperature, duration of reaction and work-
up because of potential hydrolysis except for a few as explained
below.
C48H84N18O18S6Zn3: C, 36.36; H, 5.34; N, 15.91; Zn, 12.11. Found:
C, 36.48; H, 4.92; N, 15.52; Zn, 12.60%. 5 was recrystallized in
H2O/MeOH (3:1) affording colourless blocks, after slow evapora-
tion for about two weeks, of formula [Zn3(L4)6(H2O)6] (6) whose
structure was determined by X-ray crystallography.
[Zn(L1)2(anion)2]ꢀSolv complexes were obtained as a colourless
oil (1, anion = OAc, Solv = 0) or a white precipitate (2, anion = Cl,
Solv = 3 MeOH). Their formula was derived after characterization
by NMR, IR, MS, CHN and TGA analyses. Zinc coordination exclu-
sively occurs through nitrogen atoms of the triazole unit because
the ester functionality is not affected, as concluded by IR and
NMR spectroscopies. Prolonged stirring of reaction mixture of
1–2 leads to isolation of white precipitate which from NMR and
IR studies was found to be a ZnII complex including an hydrolyzed
ligand (L2). Complex 3 was obtained as white powder. Here un-
like 1 and 2, the coordination competition between the triazole
and the carboxyl group is in favour of the latter group through
deprotonation as concluded by NMR. The strong absorption of
carboxylic group around 1735 cmꢁ1 in L2 was not only shifted
to 1743 cmꢁ1 but appeared with reduced intensity as seen by IR
spectroscopy further supports this formula [Zn(L2)2]ꢀCH3OH. A
TGA analysis also supported the presence of a non-coordinated
methanol molecule.
[Zn(L3)2Cl2] (4) was obtained as a yellow oil and characterized
by mass spectrometry. Reaction of Zn(OAc)2ꢀ2H2O with two equiv.
of L3 afforded too a yellow oil. However, the susceptibility of the
ester functionality towards decarboxylation/hydrolysis was evi-
dent from ESI-MS as only a noticeable peak at m/z = 392 was found,
corresponding to [Zn(L2)(OAc)], a breakdown product. Continua-
tion of the reaction leads to complete hydrolysis and decarboxyl-
ation within 1 h giving a white precipitate which was analysed
as 3.
3.2.6. [Zn(L5)2(OAc)2] (7)
A qualitative test has been made to check the coordinating abil-
ity of L5 to zinc. The reaction mixture of L5 (25 mg, 0.11 mmol) and
Zn(OAc)2ꢀ2H2O (12.47 mg, 0.057 mmol) salt was stirred in CDCl3 at
r.t. for 20 min. before recording 1H NMR. All signals undergo down-
field shift relative to ligand (d = 8.80(s), 4.62(d), 4.4–4.5(m), 1.32(t)
and acetate at 1.95) along with some breakdown products. The
shift is higher for triazole proton which is most likely coordinated
to zinc. Continuation of reaction leads to appearance of more
breakdown products as seen in NMR. The composition was con-
cluded based on a mass spectral peak around 562 which corre-
sponds to [M-OAc].
4. Single crystal X-ray diffraction
X-ray diffraction data were collected at 120 K for 6 with a
MAR345 image plate using Mo K
a (k = 0.71069 Å) radiation. The
crystal was chosen, transferred to inert oil and mounted to the cold
N2-gas stream for flash cooling. The unit cell parameters were re-
fined using all the collected spots after the integration process.
The data were not corrected for absorption, but the data collection
mode partially takes the absorption phenomena into account. The
structure was solved by direct methods and refined by full-matrix
least-squares on F2 using SHELXL97 [19]. Non-hydrogen atoms were
refined with anisotropic temperature factors. Hydrogen atoms
were placed at calculated positions refined in the riding mode with
isotropic temperature factors fixed 1.2 times U(eq) of the parent
atoms (1.5 times for the methyl group).
[Zn3(L4)6(MeOH)6] (5) could be obtained as a white crystalline
precipitate after having reacted Zn(OAc)2ꢀ2H2O with two equiv of
L4. Absence of acetate anion was confirmed by NMR and IR spec-
troscopy. Carboxylic stretching in L4 found at 1712 cmꢁ1 in the
IR spectrum, is no longer observed in 5. Instead, a broad band
around 1647 cmꢁ1 is detected which could be either due to coordi-
nation to zinc or involvement in H-bonding interactions (Fig. S1).
Crystal structure determination (vide infra) cleared this ambiguity
as the carboxylic group was found to be not involved in coordina-
tion and actually present in a deprotonated form.
5. Results and discussion
5.1. Synthesis and characterization
Amine derivatization into heterocycles, particularly tetrazole
and 1,2,4-triazole, is greatly sought in coordination chemistry
due to their diverse applications [20–22]. Whereas the Bayer meth-
od [23] was routinely employed for 1,2,4-triazole synthesis, ‘trans-
amination’ was proved to be an advantageous synthetic strategy to
derivatize mainly primary amine into a 1,2,4-triazole [15]. Amine
exchange process with glycine was successfully carried out in a
single step reaction without chromatographic purification [9].
Moderate yield led us to revisit the synthesis and to employ an es-
ter of glycine precursor affording L1 which can be easily hydroly-
sed to 4H-1,2,4-triazol-4-yl acetic acid (L2). This procedure not
only improved the overall synthetic method but also introduced
a versatile precursor in coordination chemistry [10,11]. Scheme 1
gives an overview of the transformed amino acids via the transam-
ination process. L1, L3 and L5 were prepared using the standard
protocol. L2 could be obtained by hydrolysis of L3 (Scheme 2)
and L4 was obtained without any catalyst [9]. Two bulky amines,
namely tetraethyl aminomethyldiphosphonate [24,25] and triethyl
aminocitrate [26,27] only provided a limited amount of triazoles
L6 and L7, which may be due to steric factors associated with
the reactants. Indeed, the amino acid precursors did not react nei-
SEM images (Fig. 1) reveal the morphology of microcrystals
(ꢂ400 nm thickness and ꢂ1.74
lm width) in 5. Most of crystals ap-
pear bent probably due to high vacuum conditions in the SEM
instrument where solvent loss is expected. TGA (Fig. S1) of air
dried sample shows in a first step, loss of three molecules of MeOH
and further, the desolvated complex decomposes in two steps. L4
shows fluorescence emission around 450 nm which is blue shifted
to 425 nm in 5 with increased intensity. Such emission band in 5 is
assigned to intraligand charge transfer (Fig. 1). The enhancement
of fluorescence may be attributed to ligand chelation to metal cen-
tre which effectively increases the rigidity of the polynuclear com-
plex and reduces the loss of energy by vibrational motion [28].
Recrystallization of 5 in a water/methanol medium led to the tri-
nuclear complex 6 where the terminal bound MeOH molecules
were replaced by water molecules as shown below by X-ray dif-
fraction. [Zn(L5)2(OAc)2] (7) was obtained by reacting L5 with
Zn(OAc)2ꢀ2H2O in CDCl3, and its formula determined by mass
spectrometry.