New silver(I) pyridinecarboxylate complexes: Synthesis, characterization, and antimicrobial therapeutic potential

Article abstract of DOI:10.1080/00958972.2014.906588

Silver(I) pyridinecarboxylates (AgPIC (1), AgNIC (2), [Ag(HDIPIC)]0. 75H₂O (3), PIC = picolinate, NIC = nicotinate, HDIPIC = dipicolinate) were prepared by solvothermal syntheses and their characterization were completed by elemental, spectral, and thermal analyses. To assign the pyridinecarboxylate coordination mode in the complexes, detailed mid-infrared spectral data and Δ(as-_s) comparisons were accomplished. In addition, silver(I) pyridinecarboxylate antimicrobial activities and stability by ¹H NMR spectra were determined. Moreover, the spectral, thermal, and antimicrobial properties of silver(I) and previously prepared zinc(II) pyridinecarboxylates were compared and discussed. 2014

Full text of DOI:10.1080/00958972.2014.906588

This article was downloaded by: [University Of South Australia Library]
On: 11 August 2014, At: 13:16
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Coordination Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gcoo20
New silver(I) pyridinecarboxylate
complexes: synthesis, characterization,
and antimicrobial therapeutic potential
Z. Vargováa, M. Almášia, D. Hudecováb, D. Titkováa, I. Rostášováa,
V. Zeleňáka & K. Györyováa
a Faculty of Science, Department of Inorganic Chemistry, P. J.
Šafárik University, Košice, Slovak Republic
b Department of Biochemistry and Microbiology, Slovak University
of Technology, Bratislava, Slovak Republic
Accepted author version posted online: 20 Mar 2014.Published
online: 17 Apr 2014.
Click for updates
To cite this article: Z. Vargová, M. Almáši, D. Hudecová, D. Titková, I. Rostášová, V. Zeleňák &
K. Györyová (2014) New silver(I) pyridinecarboxylate complexes: synthesis, characterization, and
antimicrobial therapeutic potential, Journal of Coordination Chemistry, 67:6, 1002-1021, DOI:
10.1080/00958972.2014.906588
To link to this article: http://dx.doi.org/10.1080/00958972.2014.906588
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Journal of Coordination Chemistry, 2014
Vol. 67, No. 6, 1002–1021, http://dx.doi.org/10.1080/00958972.2014.906588
New silver(I) pyridinecarboxylate complexes: synthesis,
characterization, and antimicrobial therapeutic potential
Z. VARGOVÁ*†, M. ALMÁŠI†, D. HUDECOVÁ‡, D. TITKOVÁ†, I. ROSTÁŠOVÁ†,
V. ZELEŇÁK† and K. GYÖRYOVÁ†
†Faculty of Science, Department of Inorganic Chemistry, P. J. Šafárik University, Košice,
Slovak Republic
‡Department of Biochemistry and Microbiology, Slovak University of Technology, Bratislava,
Slovak Republic
(Received 13 November 2013; accepted 26 February 2014)
Silver(I) pyridinecarboxylates (AgPIC (1), AgNIC (2), [Ag(HDIPIC)]·0.75H2O (3), PIC = picolinate,
NIC = nicotinate, HDIPIC = dipicolinate) were prepared by solvothermal syntheses and their charac-
terization were completed by elemental, spectral, and thermal analyses. To assign the pyridinecar-
boxylate coordination mode in the complexes, detailed mid-infrared spectral data and Δ(νas − νs)
comparisons were accomplished. In addition, silver(I) pyridinecarboxylate antimicrobial activities
and stability by 1H NMR spectra were determined. Moreover, the spectral, thermal, and antimicro-
bial properties of silver(I) and previously prepared zinc(II) pyridinecarboxylates were compared and
discussed.
*Corresponding author. Email: zuzana.vargova@upjs.sk
© 2014 Taylor & Francis

Silver(I) pyridinecarboxylate
1003
Keywords: Silver(I) complexes; Pyridinecarboxylic acids; Mid-IR spectra; 1H NMR spectra; Thermal
analysis; Antimicrobial activity
1. Introduction
The vast majority of antimicrobial drugs used to date are purely organic (synthetic or natu-
ral) compounds. However, resistance of pathogens towards currently used antibiotics is evi-
dent [1]. Bioinorganic chemistry is an emerging field in medicinal chemistry, which offers
the biological (and therapeutic) potential of inorganic complexes [2–4]. Metal compounds
(Zn(II), Al(III), Ag(I), etc.) play significant roles during microbial infection treatment [5].
As a result of their different coordination geometries, chemical properties, and reactivities,
metal complexes offer a wide spectrum of functional groups unexplored in modern drug
design and development [6].
The carboxylic (mainly aromatic – benzoic or salicylic) acids as O-donors are often used
as antimicrobial agents during food preservation (sodium benzoate with E number E211)
[7] or as anti-inflammatory drugs in cosmetics [8].
Pyridinecarboxylic acids as N-, O-donors are significant biomolecules. Picolinic acid
[pyridine-2-carboxylic acid or HPIC, scheme 1(a)] as a catabolite of the amino acid trypto-
phan is a chelating agent of chromium, zinc, manganese, copper, iron, and molybdenum in
the human body [9]. It is present in dietary additives as a carrier of divalent zinc and
chromium cations [10]. Nicotinic acid (niacin) [pyridine-3-carboxylic acid or HNIC, scheme
1(b)] is a water-soluble essential vitamin for redox [11, 12] and non-redox [13, 14]
reactions. Dipicolinic acid [pyridine-2,6-dicarboxylic acid or H2DIPIC, scheme 1(c)]
composes 5 to 15% of the dry weight of bacterial spores [15]. Therefore, it can be used as
an indicator of spores in hospitals, childcare centers, dentists’ offices, nursing homes, and
spacecrafts [16].
Their prevalent coordination modes are N-, O-chelate for picolinate [scheme 2(a)] and
dipicolinate [scheme 2(c)] and N-, O-bridging for nicotinate [scheme 2(b)]. Commonly pre-
ferred coordination modes registered in CCDC database are shown in scheme 2.
Ag(I) pyridinecarboxylates, [Ag(HPIC)(PIC)]⋅H2O [17], catena-H[Ag(NIC)2] [18],
catena-[Ag(NIC)] [19], and Ag(II) pyridinecarboxylate [Ag(DIPIC)2]⋅H2O [20] were previ-
ously prepared and their composition and silver(I) coordination mode confirmed by crystal
structure determination (registered in CCDC). Spectroscopic studies of Ag(picolinate) were
noted and compared with Fe(III), Zn(II), Cu(II), and Ni(II) picolinates [21]. Moreover,
Abarca et al. [22] used ν(COO−) separations for pyridinecarboxylate bond determination.
The Ag–COO− bond was determined as ionic, since the wavenumber was 1610 cm−1 or
lower. Higher COO− group wavenumbers would indicate an increase in the covalent charac-
ter of the Ag–COO− bond. In addition, symmetrical vibrations at 1450–1350 cm−1 were
used for correlation between bond character and Δ(νas − νs) variations. When the differences
in wavenumbers increase, bonding among the metal and the carboxylate groups becomes
more covalent. Thus, their AgPIC (composition stoichiometry: Ag(PIC)2⋅H2O) complex
(Δ = 229 cm−1) provides mostly covalent bonding and AgNIC (composition stoichiometry:
Ag(NIC)2) complex (Δ = 208 cm−1) an ionic bond. Moreover, these results are in accord
with X-ray characterizations of catena-H[Ag(NIC)2] (Ag–O distance is 2.80–2.83 Å), which
is unusually long in comparison to [Ag(HPIC)(PIC)]⋅H2O (2.524 Å) [22].

1004
Z. Vargová et al.
Silver and its compounds have long been used as antimicrobial agents. Silver sulfadiazine
insoluble polymeric complex (sulfadiazine = N,O-donor) is a widely used broad-spectrum
antibiotic [23, 24] which slowly releases Ag(I) in the wound [5]. The influence of silver
coordination mode and donor type to silver antimicrobial agents activity was analyzed in lit-
erature [25].
Silver(I) pyridinecarboxylates’ {AgNIC (as Ag(NIC)2), AgPIC (as Ag(PIC)2⋅H2O),
AgISONIC, AgQUINOL, AgLUTIDIN, and AgISOCINCHOM (ISONIC = isonicotinate,
QUINOL = quinolinate, LUTIDIN = lutidinate, ISOCINCHOM = isocinchomeronate)} anti-
bacterial behavior (selected bacteria Escherichia coli and Streptococcus agalactiae) was
previously analyzed [22]. Their antifungal activity was not observed until now.
Zn(II) pyridinecarboxylates were previouly prepared and their crystal structures are
recorded in CCDC with pyridinecarboxylate coordination modes a, b, c (scheme 2). More-
over, [Zn(NIC)2(H2O)4], [Zn(PIC)2(H2O)2]⋅2H2O, and [Zn(HDIPIC)2]⋅3H2O were synthe-
sized to correlate their thermal and spectral properties with crystal structures [26].
Surprisingly, zinc(II) pyridinecarboxylate biological activity was not detected until now.
To prepare silver(I) pyridinecarboxylates with perspective antimicrobial properties, we
isolated AgPIC (1), AgNIC (2), and [Ag(HDIPIC)]⋅0.75H2O (3). Unfortunately, all attempts
to obtain single crystals failed. Therefore, their compositions and molecular structures were
described by indirect methods, elemental, spectral, and thermal analyses. The pyridinecar-
boxylate coordination was assigned by detailed mid-infrared spectral data and Δ(νas − νs)
values; comparisons among free ligands and their Ag(I) complexes and sodium salts were
accomplished. Moreover, we compared their spectral and thermal properties with Zn(II)
analogs. [Zn(PIC)2(H2O)2]⋅2H2O (4), [Zn(NIC)2(H2O)4] (5), and [Zn(HDIPIC)2]⋅3H2O (6)
were prepared in accord with our previous procedure [26]. The zinc(II) and silver(I) com-
plexes’ antimicrobial activities are discussed.
2. Experimental
2.1. Materials and methods
The pyridinecarboxylic acids (scheme 1), tetramethylammonium hydroxide pentahydrate
((CH3)4N(OH)·5H2O) were obtained from Sigma-Aldrich and AgNO3 from Lachema com-
panies. All chemicals were analytically pure and used without purification.
Scheme 1. The formulas of (a) picolinic acid, (b) nicotinic acid, and (c) dipicolinic acid.

Silver(I) pyridinecarboxylate
1005
Scheme 2. Picolinate (a), nicotinate (b), and dipicolinate (c) coordination modes in CCDC.
Scheme 3. The molecular diagram of 1, 2, and 3 derived from spectral studies. (a) AgPIC (1), (b) AgNIC (2),
and (c) [Ag(HDIPIC)]·0.75H2O (3).

1006
Z. Vargová et al.
Infrared spectra of the compounds were recorded on an Avatar FT-IR 6700 spectrometer
from 4000 to 400 cm−1 using ATR (attenuated total reflectance) technique.
1H NMR spectra were recorded in DMSO-d6 with a Varian Mercury Plus 400
spectrometer at 400 MHz using TMS as the internal reference. Before NMR experiments,
fresh samples of 1, 2, and 3 were dissolved for half an hour by ultrasonic homogenizer.
After the 1H NMR experiments, the samples were kept in the dark for 96 h and the
measurements were repeated.
The elemental analysis was performed with CHNOS Elemental Analyzer vario MICRO
from Elementar Analysensysteme GmbH. The TG/DTG and DTA measurements were car-
ried out using TA instruments Netsch 409 PC. The mass of the samples was 15–20 mg.
Samples were heated in air (50 cm3 min−1) with heating rate 9 °C min−1 from 25 to 600 °C.
2.2. Preparation of the Ag(I) complexes
2.2.1. AgPIC (1) and AgNIC (2) complexes syntheses. Silver nitrate (139 mg AgNO3,
0.818 mM) with picolinic acid (nicotinic acid) (100 mg C5H4N(COOH), 0.812 mM) was
strirred in DMF (10 mL). After dissolution, the reaction mixture was placed in a 40 mL Parr
Teflon-lined stainless-steel vessel, which was heated to 90 °C with heating rate of
3 °C min−1 for 36 h. Then the reaction mixture was cooled to 70 °C with cooling rate of
0.1 °C min−1 and left at temperature for 12 h. Finally, the mixture was stepwise cooled to
room temperature at 0.1 °C min−1. Dry products were used for further characterization.
Anal. Calcd for AgC6H4NO2 (molar mass: 228.98 g M−1) (98 mg, 52% yield (1)): C,
31.34%; H, 1.75%; N, 6.09%. Found: C, 31.02%; H, 1.83%; N, 6.03%. Anal. Calcd for
AgC6H4NO2 (molar mass: 228.98 g M−1) (117 mg, 62% yield (2)): C, 31.34%; H, 1.75%;
N, 6.09%. Found: C, 31.14%; H, 1.68%; N, 6.22%.
2.2.2. [Ag(HDIPIC)]·0.75H2O (3) synthesis. Silver nitrate ((139 mg AgNO3, 0.818 mM),
dipicolinic acid (50 mg C5H3 N(COOH)2, 0.299 mM), and tetramethylammonium hydroxide
pentahydrate (57 mg N(CH3)4OH·5H2O, 0.315 mM) were dissolved in 15 mL solvent mix-
ture (volume ratio, ethanol : water, 1 : 1), placed in a 40 mL Parr Teflon-lined stainless-steel
vessel, heated to 60 °C with heating rate of 3 °C min−1 for 36 h, and then slowly cooled at
1 °C min−1 to room temperature. White powder of 3 was separated by filtration, washed by
ethanol, and dried. Anal. Calcd for AgC7H5.5O4.75 N (molar mass: 287.49 g M−1) (58 mg,
68% yield): C, 29.24%; H, 1.93%; N, 4.87%. Found: C, 29.05%; H, 1.90%; N, 4.85%.
2.3. Antimicrobial activity
The antibacterial activities of the Zn(II) and Ag(I) pyridinecarboxylate complexes and free
ligands (picolinic, nicotinic, and dipicolinic acids (scheme 1)) were evaluated by micro-dilu-
tion using G+ bacteria Staphylococcus aureus CCM 3953 and G− bacteria E. coli CCM
3988 [27]. The effects of these compounds on the growth of yeasts Candida parapsilosis
were determined by macro-dilution in L-shaped tubes adapted for direct measurement of
absorbance [28]. Cultures of bacteria (in Mueller–Hinton growth medium) and yeasts
(Sabouraud’s growth medium) were incubated under vigorous shaking. The effects of the
compounds on growth of filamentous fungi Rhizopus oryzae CCM F-8284, Alternaria
alternata CCM F-128, and Microsporum gypseum CCM F-8342 were observed by macro-
dilution on solidified broth medium during static culturing [29, 30] and the diameters of

Silver(I) pyridinecarboxylate
1007
growing fungal colonies were measured at intervals. Chromatographically pure compounds
were dissolved in DMSO. Its final concentration never exceeded 1.0 vol. % in either control
or treated samples. Concentration of the tested compounds was 0.1 × 10−3−2.0 mM dm−3 in
all experiments. The antimicrobial activity of the tested compound was characterized by
IC50 values (concentration of a compound which in comparison to the control inhibits the
growth of model microorganisms to 50%) and also by the minimal inhibitory concentration
(MIC) values (MIC of a compound which inhibits microbial growth by 100%). The IC50
and MIC values were read from toxicity curves. MIC experiments on subculture dishes
were used to assess the minimal microbicidal concentration (MMC). Subcultures were pre-
pared separately in Petri dishes containing appropriate agar growth medium, and incubated
at 30 °C for 48 h (bacteria, yeasts) and 25 °C for 96 h (filamentous fungi). The MMC value
was taken as the lowest concentration which showed no visible growth of microbial colo-
nies on the subculture dishes.
3. Results and discussion
Ag(I) pyridinecarboxylates were previously prepared by silver(I) salt and pyridinecarboxyl-
ate (or its acid) reaction at ambient temperature and atmospheric pressure in aqueous solu-
tion: silver(I) salts (nitrate, acetate, and fluoride) and nicotinic acid (molar ratio 1 : 2) from
deionized water provided catena-H[Ag(NIC)2] [18]; catena-{NH4[Ag(NIC)2]·H2O} recrys-
tallization from water containing sufficient ammonia provided catena-[Ag(NIC)] [19]. We
used solvothermal conditions for new silver(I) pyridinecarboxylate preparation. Elemental,
spectral, and thermal analyses (see below) confirm the formula of AgPIC (1), AgNIC (2),
and [Ag(HDIPIC)]·0.75H2O (3) from mixtures acquired at solvothermal conditions.
3.1. IR spectral study
Detailed analyses of IR spectra for 1, 2, and 3 were used to assign their coordination. In
order to describe obvious changes, we compared IR spectra of free pyridinecarboxylates
and their binary complexes. Significant absorptions are noted in table 1. More visual com-
1
parison is shown in figures 1–3. Moreover, H NMR spectral data comparisons were carried
1
out in order to indicate molecular structure and stability of 1, 2, and 3. H NMR spectra of
free HPIC, HNIC, and H2DIPIC and AgPIC (1), Ag(NIC) (2), and [Ag(HDIPIC)]⋅0.75H2O
(3) immediately after synthesis and after 96 h are plotted in figures 4–6. Assignment of the
proton chemical shifts is shown directly in figures 4–6.
3.1.1. Free ligands. Free ligand IR spectra (figures 1–3) indicate that they associate by
strong hydrogen bonds and therefore exist in monomeric (picolinic acid) and dimeric forms
(nicotinic, dipicolinic acid). The significant ν(C=O) is shifted to lower values in the order
picolinic (1708 cm−1, intramolecular hydrogen bonding), nicotinic (1693 cm−1, intermolecular
hydrogen bonding), and dipicolinic acid (1689 cm−1, intra- and intermolecular hydrogen bond-
ing). Broad medium signals at 2700–1800 (HNIC), 2800–1900 (HPIC), and 2900–2000
(H2DIPIC) cm−1 are caused by carboxylic O–H stretching vibrations connected to strong
hydrogen bonds, similar as Käll [18] noted for nicotinic acid. In addition, the absorption bands
with wavenumber (νas(COO−)/νs(COO−) 1604/1450 (picolinic acid), 1592/1414 (nicotinic

1008
Z. Vargová et al.
Table 1. IR spectral data of free pyridinecarboxylic acids and their silver complexes (assignments, wavenumbers
[cm−1], and intensities).
Wavenumbers [cm−1] and intensities
Assignments
[Ag(HDIPIC)]
HPIC
AgPIC
HNIC
AgNIC
H2DIPIC
⋅0.75H2O
ν (OH)
ν (CH)
–
3448(m, br)
3045(m),
2998(w)
–
3448(m, br)
3043(w),
3069(w),
3082(w)
–
–
3520(m)
3100(w),
3079(w)
3114(m)
3068(w)
3065(w)
ν (C=O)
1708(m)
1604(m)
1592(m),
1570(m),
1525(m)
1450(m)
1290(m)
–
1693(s)
1592(m)
1583(m)
1689(s)
–
1574(m),
1453(m)
1718(m)
1563(s)
1607(s),
1582(s)
νas (COO−)
ν (C=C)
1611(s)
1585(s),
1565(s),
1421(w)
1393(s)
–
1594(s),
1550(s)
νs (COO−)
ν (C–O) +
δ(OH)
1414(m)
1284(s)
1385(s)
1408(m)
1254(m)
1375(s)
1234(s)
δ (CCH)
1084(m),
960(m)
1167(w),
1087(w),
1045(m)
742(m),
698(m)
705(s)
1172(m),
1102(m),
1072(m)
740(s)
1196(w),
1115(w),
1089(w)
759(m)
1155(m),
1084(m)
1182(m),
1158(m),
1085(m)
757(s)
γ (CCH)
742(s),
672(s)
702(s)
745(s)
δ (COO−)
688(s),
637(s)
705(m)
691(s),
645(s)
698(s)
Note: s – strong, m – medium, w – weak, br – broad.
Figure 1. FT-IR spectra comparison of free HPIC and AgPIC.
acid), and 1574/1408 (dipicolinic acid) cm−1) confirm the carboxylate asymmetric and sym-
metric vibrations. All further absorption bands are in agreement with published results [18].

Silver(I) pyridinecarboxylate
1009
Figure 2. FT-IR spectra comparison of free HNIC and AgNIC.
Figure 3. FT-IR spectra comparison of free H2DIPIC and [Ag(HDIPIC)]⋅0.75H2O.

1010
Z. Vargová et al.
1H NMR spectra of free ligands (figures 4–6) confirm proton chemical shifts are in agree-
1
ment with Spectral Database for Organic Compounds [31]. H NMR spectra of silver(I)
complexes indicate their stability for 96 h.
3.1.2. HPIC, AgPIC (1), HNIC, and AgNIC (2). The silver(I) picolinate and nicotinate
IR spectra are similar. Therefore, common disscussion is offered. Comparing IR spectra of
the picolinic (nicotinic) acid and their silver(I) complexes (figures 1 and 2; table 1), signifi-
cant changes were observed, mainly under wavenumber 1750 cm−1 that indicate interactions
between Ag(I) and pyridinecarboxylates. Very strong absorption at 1611 (1594) cm−1 was
assigned to asymmetric stretch, νas(COO−). Strong signals at 1585, 1565, and 1550 cm−1
belong to ν(C=C)ar. Carboxylate symmetric stretch νs(COO−) are at 1393 (1385) cm−1.
Both deformation vibrations were observed, the in-plane bending modes δ(CCH) from
1200 to 1040 cm−1 and out-of-plane bending modes γ(CCH) from 740 to 690 cm−1.
Kalinowska et al. [21] presented similar wavenumbers, intensities, and assignments for
picolinic acid and AgPIC complex.
To recognize PIC and NIC in silver(I) complexes from IR spectra, comparison was done
from 1450 to 950 cm−1 [figure 7(a)]. The differences between 2- and 3-substituted pyridine
derivatives can be identified by C–H in-plane bending vibrations of the pyridine ring. These
vibrations are at 980–1300 cm−1. The ring modes 1, 12, 18b, 9a, 15, 3 [figure 7(b)] and
their absorption band positions in IR spectra are important makers which distinguish the
picolinate and nicotinate molecules in their silver complexes. Park et al. [32] investigated
adsorption of picolinic and nicotinic acids on silver sol surface at various pH values corre-
sponding to cationic, zwitterion (N-protonated carboxylate structure), and anionic forms
with simultaneous measurement of Raman spectra. Published results for anionic forms
(NIC−, PIC−) were used for correlation of the silver(I) complexes in this study. The ring
vibrations at 1022(1), 1036(12), 1150(9a), 1196(15), and 1234(3) cm−1 appeared in AgNIC
spectra of our complex [figure 7(a) solid line]. Values correlate very well with reported val-
ues 1031(1), 1041(12), 1154(9a), 1196(15), and 1236(3) cm−1 for NIC− [31]. The ring C–H
vibrations at 995(1), 1045(12), 1085(18b), 1144(18b), 1254(15), and 1284(3) cm−1 for Ag-
PIC [figure 7(a) dashed line] correlate with 1002(1), 1048(12), 1093(18b), 1150(18b), 1256
(15), and 1292(3) cm−1 values noted for PIC− [31], respectively. However, ring mode 9a
was not observed for PIC− [32], but new ring mode 18b occurred. Based on the above com-
parison, the presence of picolinate and nicotinate molecules in silver complexes can be dis-
tinguished.
From Δ (Δ = (νas(COO−) − νs(COO−))) [33, 34], the carboxylate coordination can be
indicated. The Δ values 218 (209) cm−1 indicate monodentate carboxylate in AgPIC
(AgNIC). To explain the observation, NaPIC (NaNIC) IR spectral data were also recorded
(NaPIC: νas(COO−) = 1606, νs(COO−) = 1412, Δ = 194 cm−1; NaNIC: νas(COO−) = 1613,
νs(COO−) = 1408, Δ = 205 cm−1). Comparing ours and published data (Δ = 217 cm−1 for
AgPIC, Δ = 223 cm−1 for NaPIC [21], Δ = 196 cm−1 for NaPIC, Δ = 206 cm−1 for NaNIC
[35]), ionic coordination of silver is preferred with particular monodentate carboxylate bind-
ing [scheme 3(a) and (b)], in agreement with thermal analysis (see below). Silver is chelated
1
through pyridine nitrogen and oxygen carboxylate in AgPIC [scheme 3(a)] as the H NMR
study also indicates (figure 4, Δδ(Hd) is 0.11 ppm, Δδ(Hd) = δ(Hd) free ligand – δ(Hd) com-
plex, Hd is influenced by deprotonation of pyridine nitrogen and its coordination [36]). Sim-
ilar 6-methylpicolinate (6-MePIC) coordination was observed in [Ag(6-MePIC)

Silver(I) pyridinecarboxylate
1011
(6-MeHPIC)] [37]. However, similar ethyl nicotinate (NICEt) provides N-pyridine coordina-
tion to silver(I) in [Ag(NICEt)]NO3 [38].
Comparing Δ values with similar zinc(II) complexes (Δ {for [Zn(NIC)2(H2O)4]} = 180
and {for [Zn(PIC)2(H2O)2]⋅2H2O} = 135 cm−1 [26], they are higher. These higher values
indicate particular covalent character of carboxylate in silver(I) picolinate and nicotinate
complexes, in agreement with Abarca’s observation [22]. The chemical shift change of
picolinic Ha (figure 4, Δδ(Ha) = 0.09 ppm) also confirms particular oxygen carboxylate
interaction with silver. Similar differences were observed in picolinate connection to zinc
[36]. Unfortunately, similar chemical shift differences were not observed in the silver(I)
Figure 4. 1H NMR spectra comparison of free HPIC and AgPIC.

1012
Z. Vargová et al.
nicotinate complex (figure 5) and zinc complexes [36]. The reduced Δ (from IR data) for
[Zn(NIC)2(H2O)4] is explained by carboxylate hydrogen bonds [26]; the low Δ value for
[Zn(PIC)2(H2O)2]⋅2H2O is explained by chelate coordination through pyridine nitrogen and
carboxylate oxygen and strong hydrogen network presence [26].
3.1.3. H2DIPIC, [Ag(HDIPIC)]⋅0.75H2O (3). Contrary to 1 and 2, IR spectra for 3
(figure 3) are different. The medium broad signal (3000–2000 cm−1) indicates the presence
of the carboxylic O–H with strong hydrogen bonds. Simultaneously, the signal at
1718 cm−1 affirms the carbonyl presence in 3. The in-plane bending modes δ(CCH) in
wavenumber ranging from 1200 to 1040 cm−1 are more intense.
Figure 5. 1H NMR spectra comparison of free HNIC and AgNIC.

Silver(I) pyridinecarboxylate
1013
Comparing the position of free ligand (figure 3; table 1) absorptions, significant changes
were observed in free ligand and [Ag(HDIPIC)]⋅0.75H2O spectra. The asymmetric and
symmetric stretches at 1563 and 1375 cm−1, respectively, confirm carboxylate coordination
1
to silver(I). Comparison of H NMR spectra (figure 6 of free dipicolinic acid and its silver
(I) complex) indicates significant change in signals. These differences support silver(I) dipi-
colinate complex formation similar to zinc(II) dipicolinate [36]. The Δ comparison between
sodium dipicolinate (Na2DIPIC: νas(COO−) = 1579, νs(COO−) = 1387, Δ = 192 cm−1) and 3
(Δ = 188 cm−1) suggests combination of chelate and bridging coordination [scheme 3(c)].
Figure 6. 1H NMR spectra comparison of free H2DIPIC and [Ag(HDIPIC)]⋅0.75H2O.

1014
Z. Vargová et al.
Dimethyl dipicolinate (DIPICMe) and dipicolinate N-oxide (DIPICN-O) coordinate silver(I)
by similar chelate coordination in catena-[Ag(DIPICMe)NO3] [39] and catena-[Ag2(DI-
PICN-O)] [40]. Distorted tetrahedral geometry around silver(I) is by two oxygens of nitrates
(catena-[Ag(DIPICMe)NO3]) and two kinds of Ag(I) exist in catena-[Ag2(DIPICN-O)]
[40].
Similar [Zn(HDIPIC)2]⋅3H2O provides low Δ (140 cm−1) in IR spectra [26]. Analogous
to [Zn(PIC)2(H2O)2]⋅2H2O, chelate coordination (through pyridine nitrogen and carboxylate
oxygen) and strong hydrogen bonds significantly influence Δ values [26].
3.2. Thermal study
AgPIC (1) thermoanalytical curves (TG/DTG-DTA) are shown in figure 8(a). Complex 1 is
thermophylic up to 245 °C. The first mass loss is observed from 250 to 300 °C with both
enthalpic effects, slightly endothermic (maximum at 250 °C) and slightly exothermic (maxi-
mum at 256 °C). This mass loss corresponds to pyridine release (34.7/34.0%, theor./obsd).
Carbon dioxide is released in the following decomposition at 350–500 °C. An exothermic
effect accompanies carbon dioxide release with maximum being at 440 °C. The experimen-
tal mass loss (19.1%) corresponds with calculated (18.1%). The solid residue after thermal
decomposition is silver (47.4/46.9%, theor./obsd).
Figure 7. (a) FT-IR spectra of AgPIC (dashed line) and AgNIC (solid line) from 1450 to 950 cm−1. (b)
Scheme of C–H in-plane vibration ring modes 1, 12, 18b, 9a, 13 and 15.

Silver(I) pyridinecarboxylate
1015
Figure 8. Thermoanalytical curves (TG/DTG-DTA) of (a) AgPIC, (b) AgNIC, and (c) [Ag(HDIPIC)]·0.75H2O
measured in air.

1016
Z. Vargová et al.
AgNIC (2) TG/DTG-DTA curves are shown in figure 8(b). Similar to 1, 2 thermal
decomposition is a one-step process. However, 2 is more thermophylic (270 °C) than 1
(245 °C). Nicotinate is released from the sample above this temperature. The experimental
mass loss (51.0%) is in agreement with calculated (53.0%). The organic part of thermal
pyrolysis is accompanied by an exothermic effect (250–400 °C, DTA curve maximum
330 °C) on the DTA curve. The solid residue is again silver (47.4/47.0%, theor./obsd).
[Ag(HDIPIC)]⋅0.75H2O (3) TG/DTG-DTA curves are shown in figure 8(c). The hydrated
3 is the least thermophylic (110 °C). A complex dehydration occurs from 110 to 160 °C
with DTA curve maximum at 153 °C and 0.75 water molecules released (mass loss 4.7/
4.5%, theor./obsd). The organic pyrolysis at 220–520 °C is slightly endothermic (DTA
curve maximum at 260 °C) and more significantly exothermic (DTA curve maximum 330,
440 °C). The mass loss indicates dipicolinate release (57.8/57.8%, theor./obsd). Similar to
previous cases, the solid residue is metal silver (37.5/38.4%, theor./obsd).
We compared the anhydrous zinc(II) and silver(I) pyridinecarboxylates’ thermal stability,
and the order is similar:
AgðHDIPICÞð225 ꢀCÞ\AgðPICÞð245 ꢀCÞ\AgðNICÞð270 ꢀCÞ
ZnðHDIPICÞ2ð200 ꢀCÞ\ZnðPICÞ2ð300 ꢀCÞ\ZnðNICÞ2ð390 ꢀCÞ
Zinc(II) complexes are more stable than silver(I) from carboxylate oxygen connection to
zinc(II) forming polymeric (in the Zn(NIC)2) and chelate picolinate coordination to zinc(II)
(in the Zn(PIC)2) [26]. The lowest thermal stabilities of Zn(HDIPIC)2 and Ag(HDIPIC) are
caused by C–C bonds splitting in the hydrogenpicolinate anion [26]. The prevalent ionic
coordination mode in anhydrous silver(I) picolinate and nicotinate complexes causes their
lower thermal stability than in similar zinc(II) complexes.
3.3. Antimicrobial activity
3.3.1. Zn complexes. Antimicrobial activity of free ligands and their Zn2+ complexes
(figure 9) characterized by IC50 and MIC values is summarized in table 2.
HPIC, HNIC, and H2DIPIC were antimicrobially inactive against bacteria G+ S. aureus,
G− E. coli, yeasts C. parapsilosis, and filamentous fungi R. oryzae, A. alternata,
M. gypseum. Their IC50 and MIC values are higher than 2 mM dm−3, except H2DIPIC
against yeasts C. parapsilosis – IC50 = 1.1 and MIC–2 mM dm−3.
The presence of zinc(II) in picolinate and nicotinate complexes led to increase of antibac-
terial activity. Comparing IC50 and MIC values, the zinc(II) nicotinate complex has the
highest antibacterial activity towards both bacteria: IC50 = 0.2 (S. aureus), 0.5 (E. coli) mM
dm−3, and MIC = 2 mM dm−3, with bacteriostatical effect on bacterial cells.
Similar to bacteria, zinc(II) nicotinate complex affords the highest activity against patho-
genic yeasts C. parapsilosis – IC50 = 0.23 and MIC = 0.5 mM dm−3 with fungistatic effect
on yeasts cells.
Zinc(II) nicotinate (A. alternata – IC50 = 1.3 and MIC > 2 mM dm−3) ligands nor their
zinc(II) complexes do not repress growth of filamentous fungi R. oryzae, A. alternata, M.
gypseum (IC50 and MIC > 2 mM dm−3). Comparing IC50 and MIC values, inhibition activity
of the Zn(II) complexes decreases in the order: [Zn(NIC)2(H2O)4] > [Zn(PIC)2(H2O)2]
⋅2H2O > [Zn(HDIPIC)2]⋅3H2O. Comparing Zn(II) picolinate ([(Zn(PIC)2(H2O)2]⋅2H2O) and

Silver(I) pyridinecarboxylate
1017
Figure 9. Antimicrobial activity of zinc(II) and silver(I) complexes characterized by IC50 and MIC values.
salicylate ([Zn(SALIC)2]⋅2H2O) antimicrobial activity, Zn(II) picolinate affords comparable
activity like Zn(II) salicylate [41].
3.3.2. Ag complexes. The IC50 and MIC values are noted in table 2 for free ligands and
their Ag(I) complexes (figure 9).
Growth of S. aureus and E. coli is significantly suppressed by silver(I) complexes present in
growth medium (see table 2); 50% growth inhibition of both bacteria by AgPIC, AgNIC, and
[Ag(HDIPIC)]·0.75H2O is similar, with IC50 ranging from 0.005 to 0.007 mM dm−3. Total
(100%) growth inhibition of S. aureus was observed at 0.05 mM dm−3 for all silver(I)
complexes but with bactericide effect for AgPIC and AgNIC and bacteristatic effect for
[Ag(HDIPIC)]⋅0.75H2O. Hundred percent growth inhibition of E. coli was observed for all sil-
ver(I) complexes (even at five times lower concentration of 0.01 mM dm−3) with bacteristatic
effect.
Silver(I) complexes significantly influence the growth of C. parapsilosis yeast (see table
2). Similar to bacteria, anti-yeast activity of AgPIC, AgNIC, and [Ag(HDIPIC)]⋅0.75H2O is
approximately the same, IC50 of 0.9–1.0 μM dm−3. The total growth inhibition (MIC =
0.005 mM dm−3) with fungistatic effect toward the yeast cells was noted. Comparing IC50
and MIC values, anti-yeast activity is higher than antibacterial. Similar to previous cases,
silver presence increases antifungal activity.

1018
Z. Vargová et al.

Silver(I) pyridinecarboxylate
1019
Fungi growth inhibition decreased in the order: R. oryzae > A. alternata > M. gypseum.
Antifungal activity of AgPIC, AgNIC, and [Ag(HDIPIC)]⋅0.75H2O is approximately the
same with IC50 of 0.06–0.07, MIC = 0.1 mM dm−3 (R. oryzae); IC50 of 0.07–0.09, MIC =
0.5 mM dm−3 (A. alternata) and IC50 of 0.21–0.34, MIC = 0.5–1.0 mM dm−3 (M. gypseus).
Hundred percent growth inhibition with lethal effect on R. oryzae spores was observed at
0.1 mM dm−3 complex concentration. Total growth inhibition of A. alternata by all Ag(I)
complexes with fungistatic effect on spores was recorded at 0.5 mM dm−3. The highest
growth inhibition of dermatophytic M. gypseus was observed by AgNIC.
By comparing IC50 and MIC values, we conclude that Ag(I) complexes inhibition activ-
ity against filamentous fungi decreases AgNIC > AgPIC > [Ag(HDIPIC)]·0.75H2O.
Rowan et al. [42] with similar inactive N or O-donors (imidazole, salicylic acid, 2-
methyl-5-nitroimidazole, 1-(3-aminopropyl)imidazole) tested against the pathogenic bacteria
S. aureus, E. coli, and fungal pathogen C. albicans. Their MIC values are higher than 0.05
mM dm−3. Their silver(I) complexes exhibited significantly greater antifungal
(MIC100 values from 0.1 to 4.8 μM dm−3) than antibacterial activity (MIC50 values from
0.0105 to 0.05 mM dm−3). Similar trend is observed for our silver(I) complexes
(MIC = 0.005 mM dm−3 for fungal pathogen C. parapsilosis, 0.01 and 0.05 mM dm−3 for
pathogenic bacteria E. coli and S. aureus, respectively, see table 2).
Silver(I) complexes with 2-aminopyridine and 3-aminopyridine were tested against the Gram
positive and negative bacteria and fungal pathogen [43]. Our silver(I) pyridinecarboxylate
analogs (AgPIC (1) and AgNIC (2)) are more active against E. coli (MIC = 0.01 mM dm−3)
and S. aureus (MIC = 0.05 mM dm−3) than their amino analogs (MIC = 0.054 mM dm−3
(E. coli)/0.433 mM dm−3 (S. aureus)), complex with 2-aminopyridine; MIC = 0.03 mM dm−3
(E. coli)/0.121 mM dm−3 (S. aureus), complex with 3-aminopyridine) [36].
Abarca et al. [22] tested AgNIC (composition stoichiometry Ag(NIC)2) and AgPIC (Ag
(PIC)2⋅H2O) against E. coli and S. agalactiae bacteria. Similarly, their complexes show
lower antibacterial activity (IC50 = 0.044 mM dm−3 E. coli, IC50 = 0.067 mM dm−3
S. agalactiae, AgPIC; IC50 = 0.042 mM dm−3 E. coli, IC50 = 0.042 mM dm−3, S. agalactiae,
AgNIC) than our complexes (table 2). The differences are probably caused by lower silver
(I) ion composition (29.1% Ag in Ag(PIC)2⋅H2O, 30.5% Ag in Ag(NIC)2 [22], 46.7% Ag
in AgPIC/AgNIC).
The Ag(I) pyridinecarboxylate antimicrobial activities (IC50 and MIC values) (figure 9)
comparison leads to the following order: AgNIC > AgPIC > [Ag(HDIPIC)]⋅0.75H2O, in
agreement with increasing antimicrobial activity of silver(I) complexes influenced by ligand
[22]. The AgPIC and AgNIC complexes, predominantly with ionic interaction, provide the
most efficient antimicrobial effect (alternatively, the ligand exchange reaction, between pyri-
dinecarboxylate and biological ligand, is easy), similar to Abarca’s conclusion [22]. On the
other hand, [Ag(HDIPIC)]·0.75H2O (with chelate and bridging coordination mode, see
above section 3.1.3) has the lowest antimicrobial effect.
Comparing Zn(II) and Ag(I) pyridinecarboxylate antimicrobial properties, the tested Zn
(II) pyridinecarboxylates have lower antimicrobial effect than analogous silver(I) pyridine-
carboxylates. However, the inhibition activity order is similar:
½Zn(NIC)2ðH2OÞ4ꢁ [ ½Zn(PIC)2ðH2OÞꢁ ꢂ 2H2O [ ½ZnðHDIPICÞ2ꢁ ꢂ 3H2O
Their decreased antimicrobial activity is probably caused by more stable complexes,
lower antimicrobial metal composition, or different ligand coordination.

1020
Z. Vargová et al.
4. Summary
Three silver(I) pyridinecarboxylates (AgPIC (1), AgNIC (2), [Ag(HDIPIC)]⋅0,75H2O (3))
were prepared. Spectral, elemental, and thermal analyses were used for composition confir-
mation. Moreover, IR spectra data analysis provides the coordination mode. It confirms pre-
valent ionic interaction between silver(I) and picolinate and nicotinate with particular
covalent character of interaction in the case of 2 and chelate character in 1. The combina-
tion of chelate (through pyridine nitrogen and carboxylate oxygen) and bridging coordina-
tion mode (between the two central atoms) in hydrated 3 was observed. Pyridinecarboxylate
coordination was compared to other silver(I) pyridinecarboxylate analogs (methyl and ethyl
derivatives). Similar chelate coordination behavior was observed for picolinate and dipicoli-
nate and different N-pyridine coordination in nicotinate. Thermal and structural property
correlation among zinc(II) and silver(I) complexes were offered. The anhydrous zinc(II)
pyridinecarboxylates form more stable complexes than silver(I). The silver(I) pyridinecarb-
oxylates have significantly higher growth inhibition of model bacteria, yeasts, and filamen-
tous fungi. Binding modes, antimicrobial metal, and complex stability can influence their
antimicrobial activity.
Acknowledgements
Financial support was provided by grants of the Ministry of the Education of the Slovak
Republic (VEGA 1/0366/14). The authors are very grateful to Miroslav Psotka, Mária Vilková,
and Ján Imrich from P.J. Šafárik University in Košice for the NMR spectra measurement.
References
[1] G.D. Wright. Curr. Opin. Microbiol., 13, 589 (2010).
[2] U. Schatzschneider, N. Metzler-Nolte. Angew. Chem. Int. Ed., 45, 1504 (2006).
[3] J. Lv, T. Liu, S. Cai, X. Wang, L. Liu, Y. Wang. J. Inorg. Biochem., 100, 1888 (2006).
[4] G. Jaouen, P.J. Dyson. In Comprehensive Organometallic Chemistry III, Medicinal Organometallic Chemis-
try, D. O’Hare (Ed.), pp. 445–464, Elsevier, Amsterdam (2007).
[5] I. Bertini, H.G. Gray, E.I. Stiefel, J.S. Valentine. Biological Inorganic Chemistry (Structure and Reactivity),
University Science Books, Sausalito, CA (2007).
[6] S. Sayen, A. Carlier, M. Tarpin, E. Guillon. J. Inorg. Biochem., 120, 39 (2013).
[7] H.A. Krebs, D. Wiggins, M. Stubbs, A. Sols, F. Bedoya. Biochem. J., 214, 657 (1983).
[8] P.A. Mackowiak. Clin. Infect. Dis., 31, 154 (2000).
[9] P.J. Aggett, P.K. Fenwick, H. Kirk. J. Nutr., 119, 1432 (1989).
[10] C. Dazzi, G. Candiano, S. Massazza, A. Ponzetto, L. Varesio. J. Chromatogr. B, 751, 61 (2001).
[11] T. Brody. Nutritional Biochemistry, 2nd Edn, Academic Press, San Diego, CA (1999).
[12] D. Cervantes-Laurean, N.G. McElvaney, J. Moss. In Modern Nutrition in Health and Disease, M. Shils,
J.A. Olson, M. Shike, A.C. Ross (Eds), 9th Edn, pp. 442–451, Williams & Wilkins, Baltimore, MD (1999).
[13] R. Jacob, M. Swenseid. In Present Knowledge in Nutrition, E.E. Ziegler, L.J. Filer (Eds), 7th Edn, pp. 185–
190, ILSI Press, Washington, DC (1996).
[14] M.K. Jacobson, E.L. Jacobson. Trends Biochem. Sci., 24, 415 (1999).
[15] T.A. Sliemandagger, W.L. Nicholson. Appl. Environ. Microbiol., 67, 1274 (2001).
[16] M.L. Cable, J.P. Kirby, K. Sorasaenee, H.B. Gray, A. Ponce. J. Am. Chem. Soc., 129, 1474 (2007).
[17] J.P. Deloume, R. Faure, H. Loiseleur. Acta Crystallogr., Sect. B, 33, 2709 (1977).
[18] P.O. Käll, J. Grins, M. Fahlman, F. Söderlind. Polyhedron, 20, 2747 (2001).
[19] G. Smith, A.N. Reddy, K.A. Byriel, C.H.L. Kennard. Polyhedron, 13, 2425 (1994).
[20] M.G.B. Drew, R.W. Matthews, R.A. Walton. J. Chem. Soc. A, 1405 (1970).
[21] M. Kalinowska, M. Borawska, R. Świsłocka, J. Piekut, W. Lewandowski. J. Mol. Struct., 834–836, 419
(2007).

Silver(I) pyridinecarboxylate
1021
[22] R. Abarca, G. Gomez, C. Velasquez, M.A. Paez, M. Gulppi, A. Arrieta, M.I. Azocar. Chin. J. Chem., 30,
1631 (2012).
[23] C.L. Fox, S.M. Modak. Antimicrob. Agents Chemother., 5, 582 (1974).
[24] Z. Guo, P.J. Sadler. Angew. Chem. Int. Ed., 38, 1512 (1999).
[25] S. Ahmad, A.A. Isab, S. Ali, A.R. Al-Arfaj. Polyhedron, 25, 1633 (2006).
[26] Z. Vargová, V. Zeleòák, I. Cısaøová, K. Györyová. Thermochim. Acta, 423, 149 (2004).
́
[27] S. Jantová, D. Hudecová, Š. Stankovský, K. Špirková, Ľ. Ružeková. Folia Microbiol., 40, 611 (1995).
[28] V. Betina, D. Mičeková. Z. Allg. Mikrobiol., 5, 55 (1972).
[29] D. Hudecová, S. Jantová, M. Melník, M. Uher. Folia Microbiol., 40, 473 (1996).
[30] B. Dudová, D. Hudecová, R. Pokorný, M. Mičková, M. Palicová, P. Segl’a, M. Melník. Folia Microbiol., 47,
225 (2002).
[31] Free access http://sdbs.riodb.aist.go.jp/sdbs/cgi-bin/direct_frame_top.cgi.
[32] S.M. Park, K. Kim, M.S. Kim. J. Mol. Struct., 344, 195 (1995).
[33] G.B. Deacon, R.J. Phillips. Coord. Chem. Rev., 33, 227 (1980).
[34] Z. Vargová, M. Almáši, L. Arabuli, K. Györyová, V. Zeleňák, J. Kuchár. Spectrochim. Acta Part A, 78, 788
(2011).
[35] A. Szorcsik, L. Nagy, J. Sletten, G. Szalontai, E. Kamu, T. Fiore, L. Pellerito, E. Kálmán. J. Organomet.
Chem., 689, 1145 (2004).
[36] Z. Vargová, J. Kotek, J. Rudovský, J. Plutnar, R. Gyepes, P. Hermann, K. Györyová, I. Lukeš. Eur. J. Inorg.
Chem., 25, 3974 (2007).
[37] A. Leiva, W. Clegg, L. Cucurull-Sánchez, P. González-Duarte, J. Pons. J. Chem. Crystallogr., 29, 1097
(1999).
[38] M.A.M. Abu-Youssef, R. Dey, Y. Gohar, A.A. Massoud, L. Öhrström, V. Langer. Inorg. Chem., 46, 5893
(2007).
[39] M. Hakimi, K. Moeini, Z. Mardani, E. Schuh, F. Mohr. J. Coord. Chem., 66, 1129 (2013).
[40] W.P. Wu, Y.Y. Wang, C.J. Wang, Y.P. Wu, P. Liu, Q.Z. Shi. Inorg. Chem. Commun., 9, 645 (2006).
[41] Z. Bujdošová, K. Gyoryová, J. Kovarová, D. Hudecová, L. Halás. J. Therm. Anal. Calorim., 98, 151 (2009).
[42] R. Rowan, T. Tallon, A.M. Sheahan, R. Curran, M. McCann, K. Kavanagh, M. Devereux, V. McKee.
Polyhedron, 25, 1771 (2006).
[43] M.A.M. Abu-Youssef, V. Langer, L. Ohrström. Dalton Trans., 2542 (2006).