Bis{phenyl[di(methoxyethyloxy)phosphoryl]methyl}amine as a new ligand for metal ions and cationic organic molecules

Article abstract of DOI:10.1016/j.molstruc.2011.01.016

The bis(phenylphosphorylmethyl)amine containing binding units based on "crown-ether like" ester moiety was tested as a supramolecular host molecule. The complexation properties towards metal ions (Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺, Mg²⁺, Ca²⁺, Ba²⁺) and hydrochlorides of amino acids (Lys, Arg), diethylenetriamine (2EN3A) and pentaethylenehexaamine (5EN6A) were studied. In order to assess the binding affinities of the receptor to selected guest molecules in various solvents, the ESI-MS and NMR techniques were applied. The results were also supported by theoretical studies. The ESI-MS studies revealed the selective binding of Cs⁺ and 5EN6 by the phosphonate molecule, whereas NMR investigation in solution indicated tighter association of the host-guest system obtained for Mg²⁺ and Arg. The discrepancies between the results originating from both used methods are most likely caused by influence of the solvent on intermolecular interactions.

Full text of DOI:10.1016/j.molstruc.2011.01.016

Journal of Molecular Structure 991 (2011) 18–23
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Bis{phenyl[di(methoxyethyloxy)phosphoryl]methyl}amine as a new ligand for
metal ions and cationic organic molecules
a
a
b
a
Piotr Młynarz a, , Tomasz Ptak , Anna Czernicka , Radosław Pankiewicz , Karolina Gluza ,
⇑
c
´
Dorota Zarzeczanska
a
_
´
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wrocław, Poland
b Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland
c Department of Chemistry, Sobieskiego 18/19, University of Gdansk, 80-952 Gdansk, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 May 2010
Received in revised form 14 September 2010
Accepted 12 January 2011
Available online 24 January 2011
The bis(phenylphosphorylmethyl)amine containing binding units based on ‘‘crown-ether like’’ ester moi-
ety was tested as a supramolecular host molecule. The complexation properties towards metal ions (Li+,
Na+, K+, Rb+, Cs+, Mg2+, Ca2+, Ba2+) and hydrochlorides of amino acids (Lys, Arg), diethylenetriamine
(2EN3A) and pentaethylenehexaamine (5EN6A) were studied. In order to assess the binding affinities
of the receptor to selected guest molecules in various solvents, the ESI-MS and NMR techniques were
applied. The results were also supported by theoretical studies. The ESI–MS studies revealed the selective
binding of Cs+ and 5EN6 by the phosphonate molecule, whereas NMR investigation in solution indicated
tighter association of the host–guest system obtained for Mg2+ and Arg. The discrepancies between the
results originating from both used methods are most likely caused by influence of the solvent on inter-
molecular interactions.
Keywords:
Aminophosphonate
Ionophore
NMR
ESI-MS
Ó 2011 Elsevier B.V. All rights reserved.
Diffusion coefficient
Association constants
1. Introduction
In this work we report the ‘‘second generation’’ of the host mol-
ecule having tetra-2-methoxyethyl aminophosphonate binding
Crown ethers and polyglycol podands play an important role in
supramolecular chemistry as molecular hosts for metal ions and
organic cations. These compounds are also believed to perfectly
mimic the behavior of natural ionophores [1]. Moreover, the note-
worthy features are attributed to polyoxaalkyl arms which are well
recognized binding motifs [2,3]. Their anchoring centers possess-
ing various heteroatoms may serve as a suitable polyvalent system
for metal ions chelation [4,5]. Nevertheless, there is still a strong
demand for the development of novel specific and selective hosts
for many purposes. In this light new organophosphorus com-
pounds appear to be interesting and scarcely developed class of
receptors [4].
unit. The investigations involve synthesis of the receptor, evalua-
tion of its binding properties and theoretical studies by computa-
tional methods. Application of ESI-MS spectrometry and NMR
spectroscopy enabled to determine binding properties towards se-
lected inorganic and organic cations with detailed description of
host–guest interactions.
2. Experimental
2.1. Synthesis of bis{phenyl[di(methoxyethyloxy)phosphoryl]methyl}-
amine (receptor) 1 (Scheme 1)
Recently, we have described the hybrid phosphonate host mol-
ecule suitable for metal ions binding [5]. Combining polyoxaalkyl
chains and phosphonic acid unit in one molecule allowed to obtain
a selective receptor for mono- and divalent metal ions from the
first and the second group of periodic table. Although, organic mol-
ecules possessing ammonium cation were found to not interact
with this molecule.
The chemical synthesis of the receptor 1 was carried out basing
on the literature data [6,7]. The excess of NH4OH was added to the
freshly distilled benzaldehyde (10 ml, 0.095 mole) and the mixture
was stirred under reflux for 30 min. Afterwards, the solution was
cooled, which resulted in precipitation of white solid. The obtained
product was filtered off, washed with water and dried to give inter-
mediate hydrobenzamide in a yield of 85%.
In the next step, 6 g (0.02 mole) of hydrobenzamide was dis-
solved in toluene and then 3.85 ml (0.02 mole) of the diphenyl
phosphite was added. The mixture was refluxed for 5 h and the
solvent was evaporated in vaccuo. The resulted yellow oil was
⇑
Corresponding author.
E-mail address: piotr.mlynarz@pwr.wroc.pl (P. Młynarz).
0022-2860/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2011.01.016

P. Młynarz et al. / Journal of Molecular Structure 991 (2011) 18–23
19
dissolved in acetone and cooled to 4–6 °C giving a white precipi-
tate (yield 80%). Then, the obtained product was reacted with di-
phenyl phosphite (0.02 mole) and the sequence of reaction steps
was repeated.
method (MM2). In all cases full geometry optimization was carried
out without any symmetry constraints.
The ligand–organic guest supramolecule geometries were opti-
mized by using density functional theory (DFT), with B3LYP hybrid
functional [11,12]. Quantum chemical calculations were done
using 6-31++G(d,p) basis set considering the polarization and dif-
fuse functions on all atoms. Moreover, the frequency analyses were
carried out for all the molecules to confirm that they were in the
local minima. All the calculations were performed in Gaussian 03
[13], using CPCM [14] continuum solvent models, with water as
a solvent. Atomic charges were received from natural bond orbital
analysis (NBO) [15].
Additionally, conformational analysis of the complexes formed
between aminobisphosphonate receptor and amino acids was per-
formed using simulated annealing method. The analyzed systems
were preheated to 1000 K and cooled down to 300 K. Each of the
generated structure was optimized to energy minimum using Dis-
cover module implemented in molecular modeling environment
package Insight II.
One gram of the obtained compound was transesterified with
excess of 2-methoxyethanol, which was added together with the
catalytic amount of KF and 18-crown-6 ether. The mixture was re-
fluxed for 30 min. and left at room temperature for 8 h. The volatile
components were evaporated under reduced pressure and the
resulting yellow oil was purified by HPLC. The product was ob-
tained as a mixture of diastereoisomers in the 2:1 molar ratio. They
are denoted as iii (major) and ii (minor) stereoisomer assigned
from NMR spectra.
1H NMR (MeOD): d (ppm): iii 3.26 (s, ACH3); ii 3.28 (s, ACH3); ii
3.33 (s, ACH3); iii 3.35 (s, ACH3); iii 3.42 (m, ACH2A); ii 3.46 (m,
ACH2A); iii and ii 3.57 (t, ACH2A, J = 4.5 Hz); iii 3.91 (d, JH–P
21.8 Hz, -CHP); iii 3.90 (m, ACH2A); ii 3.97 (m, ACH2A); iii 4.04
(m, ACH2A); ii and iii 4.08–4.24 (m, ACH2A); ii 4.38 (d, JH–P
17.6 Hz, -CHP); iii and ii 7.40–7.26 (m, Ar).
13C NMR (MeOD): d (ppm) iii 58.72 (dd,
=
a
=
a
a
-CHP, JC–P = 158.3 Hz,
JC–P = 17.5 Hz): iii 59.00 (s, ACH3); ii 59.09 (s, ACH3); ii 59.94 (dd,
-CHP, J = 156.8, J = 11.1 Hz); 67.08–67.41 m (ACH2A); 67.51 (bs,
3. Results and discussion
a
ACH2A) 72.43 (bs, ACH2A), 72.6 (bs, ACH2A); 129.31 (s, Ar);
129.58 (d, Ar, J = 13.7 Hz); 129.78 (bs, Ar); 129.97 (d, J = 6.0 Hz);
130.40 (s, Ar), iii 135.15 (s, Ar); ii 130.38 (s, Ar).
3.1. ESI-MS, NMR and theoretical calculation studies for the receptor
The ESI-MS studies of the free receptor revealed three signals: a
molecular signal at (+) 591[L + H]+ m/z and two other originating
from fragmentation of the molecule at (+) 393 [L-PO(R)2]+ and
(ꢁ) 531 [L-(R)]ꢁ m/z. This fragmentation pattern seems to be char-
acteristic for this compound.
31P NMR (MeOD): d (ppm): iii 24.04; ii 24.40.
2.2. ESI-MS studies
The 31P NMR investigation of the receptor showed the presence
of two diastereoisomers (see experimental section) in 2:1 molar
ratio. Theoretical calculation of the metal free receptor revealed
that the RR isomer (HOF ꢁ2056,29 kJ/mol) is more stable than RS
form (HOF ꢁ2032.76 kJ/mol).
The ESI (electrospray ionization) mass spectra were recorded on
a Waters/Micromass (Manchester, UK) ZQ mass spectrometer
equipped with a Harvard Apparatus syringe pump. The measure-
ments were performed in methanol and acetonitrile solutions for
the receptor concentration (1–5) ꢀ 10ꢁ4 mol dmꢁ1 and metal to li-
gand ratio 1:1 and 1:2. The samples were infused into the ESI
Intriguingly, the 1H- and 31P NMR titration exhibited acidic
character of the amino group (pKa > 1). There can be two explana-
tions for the low pK value of this group: (i) the attached polyglycol-
ic fragment may prompt hydrolysis of apparently bound water
molecule; (ii) the presence of 2-metoxyethyl and phenyl groups
causes strong electron withdrawing effect from central amine
group. To elucidate this issue the ‘‘one-arm’’ analog of studied
receptor was synthesized and the NMR titration was performed
(Figs. 1 and 2).
source using a Harvard pump at a rate 20 l
dm3 minꢁ1. The ESI
source potentials were: capillary 3 kV, lens 0.5 kV, extractor 4 kV,
and the cone voltage 30 V. The source temperature was 120 °C
and the desolvation temperature was 300 °C. Nitrogen was used
as a nebulizing and desolvation gas at a flow rate of 100 and
300 dm3 hꢁ1, respectively.
2.3. NMR measurements
The comparison of the titration curves support hypothesis of a
strongly withdrawing electron effect of polyglycolic arms from
amine group, because in the case of compound 1 the great change
in the chemical shift is observed, while for its acylated analog 2 not.
NMR measurements were performed on BRUKER 600 MHz
Avance II spectrometer equipped with TBO 5 mm probe with
z-gradient and temperature control unit (T = 298 0.1 K) in D2O,
MeOD CD3CN. The 1D and 2D (HMQC, COSY, TOCSY, T1-pseudo
2D) NMR techniques were applied using receptor concentration
(2–7) ꢀ 10ꢁ3 mol dmꢁ1 and metal to ligand ratio 1:1. Titration
experiment were performed in the metal to ligand ratio from 0:1
to 4:1. The diffusion coefficient determination were performed
using stimulated echo and LED pulse sequence with two spoil gra-
dients (ledgp2s) [8]. All samples were temperature equilibrated in
the spectrometer during 0.5 h. Individual calibration of the diffu-
3.2. Complexation properties of bis{phenyl[di(methoxyethyloxy)-
phosphoryl]methyl}amine
3.2.1. Towards metal ions
The presence of polyglycol units strongly assures the occur-
rence of interaction with hard sphere metal ions [3,16,17]. ESI
sion time
D and gradient pulse d values for each investigated sys-
O
tems were carried out. Chemical shifts are given in relation to TMS,
TSP, 85% phosphoric acid and D2O containing appropriate metal
perchlorate salt as external standards.
O
O
O
P
O O
2.4. Computational methods
N
O
H
The metal–ligand complexes were studied (Semiempirical PM6
method) [9] by using the MO-G for SCIGRESS program [10]. All
initial structures were optimized first by molecular mechanics
Fig. 1. The structure of one arm analog 2.

20
P. Młynarz et al. / Journal of Molecular Structure 991 (2011) 18–23
ester protons may be classified as a characteristic feature for the
25,5
25,0
24,5
24,0
23,5
23,0
22,5
22,0
first and for the second group of elements of periodic table.
In general, CIS values of CH3 groups are apparently visible for all
the investigated metal ions as one type of ‘‘binding shoulder’’
(Scheme 2) for molecule 1 (in order: Na+ > Li+ > K > Rb+ > Cs+;
Mg2+ > Ca2+ > Ba2+), while for the second type of esters group the
CIS alterations are a little for (Li+, Na+, K+, Rb+) and much bigger
for (Mg2+, Ca2+, Ba2+). The cesium ions force the change of CH3
group shift similar to the divalent ions. The most probably this
phenomenon was observable due to its great ion radius. For diva-
lent metal ions the significant CIS changes are also detected for CH2
groups in the following order: Mg2+ > Ca2+ > Ba2+ reflecting the size
of the metal ions and the ‘‘deepness’’ of interaction with ester
groups. While for the first group of elements the effect was seen
only for Li+ ions.
0
2
4
6
8
10
12
14
The chemical shift changes in 31P NMR spectra reflected the or-
der described for CH3 and CH2 groups with only exception ob-
served for Li+ ions, where phosphorus signals are much more
shifted in comparison to the rest of first group metal ions.
All these findings may suggest that alkali metal ions effectively
interact with receptor via two methoxyglycol chains located on dif-
ferent phosphorus atoms, which is accompanied by weak binding
by the second chains. Moreover, the lithium ions, as 31P NMR spec-
tra have proved, are bound in the closer proxymity to the phospho-
rus atoms (which might suggests involvement of central nitrogen
donor). The alkaline earth metal ions formed metal to ligand com-
plexes of 1:2 ratio and this is reflected by other type of binding pat-
tern. They are bound ‘‘deeper’’ by two chains indicated by arrows
in Scheme 2, but in this case the second type of arms also seem
to participate in the metal–receptor interactions. It clearly indi-
cates that ions of smaller radius are bound stronger. Additionally,
the charge of the metal ion plays important role in the ligand–
metal binding and thus divalent metal ions are bound better than
monovalent ones. This effect is, most likely, also associated with
counter ion.
In order to determine association constant two experimental
facts have to be considered. The previously performed investiga-
tions showed the lack of significant influence of 1:1 complex con-
centration (in the range 2–7 mM) on chemical shifts of protons. In
addition, 31P NMR studies appeared to be only roughly indicative,
due to the use of the mixture of diastereoisomers (Table 3). There-
fore, during the calculation of the association constants few
assumptions were done: (i) the concentration of each diastereoiso-
mer was calculated as a molar fraction taken form phosphorus
signal integration of metal free host: (ii) the assumption of forma-
tion 1:1 and 1:2 complexes was assumed on basis of the ESI-MS
studies, however, the formation of more complexes such as multi-
ple assembled polymeric structures can not be excluded (vide
supra).
pH
Fig. 2. The 31P NMR titrations of compound 1 (j and d) and 2 (
D).
studies revealed the chelation abilities of this receptor towards Li+,
Na+, K+, Rb+, Cs+, Mg2+, Ca2+ and Ba2+ ions with formation of molec-
ular complexes in 1:1 ratio (metal to ligand) for the first and 1:2 for
the second group (Table 1). Monovalent metal ions are complexed
as free ions, whereas divalent cations are bound together with
their perchlorate counterions and formed in 1:1 metal to ligand ra-
tio. This phenomenon is consisted with the results obtained for the
systems published recently [5].
The fragmentation pattern of the formed complexes could re-
flect the strength of metal binding to the receptor (Table 1). The
studied phosphonate host appears to bind most effectively Cs+
ion in ESI-MS gas-phase conditions. This is the most probably
due to best fitting of ion radius of Cs+ to the binding cavity formed
by the ligand. This also seems to support the rule, that the host,
which possesses stronger chelating abilities, preserves the molecu-
lar complex against defragmentation processes.
To prove this statement additional 1H and 31P NMR measure-
ments in solution were conducted. As an indicative factor of
host–guest (metal ions) interaction the complexation induced
chemical shift CIS (Dd) was assumed [18]. Initially, D2O was used
as a solvent. Unfortunately, in aqueous solution only very small
CISs were observed in 31P NMR spectra (up to 0.008 ppm), which
did not exceed the half-width of the phosphorus signal. This
prompted us to employ CD3OD. Admittedly, changing solvent to
methanol
Dd grew up to 0.07 ppm but during host–guest titration
the lack of curve saturation was observed. Therefore, the further
studies were performed in CD3CN. At the beginning, the heteronu-
clear NMR measurements were performed to affirm the influence
of ligand on metal binding (Table 2). All the investigated metal ions
revealed the significant changes.
All the observed changes are reflected with the approximate
log K values (Table 3), which are the highest for alkaline earth me-
tal ions. Moreover the metal–ligand interactions patterns obtained
The receptor binding abilities were also reflected in 1H NMR and
31P NMR spectra. The observed changes in CIS values observed for
Table 1
Table 2
The main peaks (m/z) and their defragmentation pattern in the ESI-MS spectra at 30 V
cone voltage upon formation of the molecular complexes with metal ions.
The heteronuclear chemical shifts observed for investigated metal
ions recorded in CD3CN*.
Cation
Main peaks (m/z)
Metal ions
Dd (ppm)
Li+
597 [L + Li]+, 393 [L-PO(OR)2]+
Li+
ꢁ0.41
Na+
K+
613 [L + Na]+, 393 [L-PO(OR)2]+
629 [L + K]+, 393 [L-PO(OR)2]+
Na+
K+
ꢁ0.46
Rb+
Cs+
675 [L + Rb]+, 393 [L-PO(OR)2]+
723 [L + Cs]+
ꢁ1.09
Rb+
Cs+
significant broadening of the signal
Mg2+
Ca2+
Ba2+
602 [2L + Mg]2+, 714 [Mg + L + ClO4]+
610 [2L+Ca]2+, 730 [Ca+L+ClO4]+, 393 [L-PO(OR)2]+
659 [2L+Ba]2+, 827 [Ba+L+ClO4]+, 393 [L-PO(OR)2]+
ꢁ0.678
Mg2, Ca2+
detected.
,
Ba2+ broadening of the line or nucleus not
*

P. Młynarz et al. / Journal of Molecular Structure 991 (2011) 18–23
21
O
reflux 30 min
N
N
+
NH4OH
O
O
toulene/reflux 5h
N
+
N
N
H P
O
O
P
O
O
O
P
O
toulene/reflux 5h
O
+
N
O
P
H
H
N
O
O
O
O
P
P
O
O
O
O
O
O
O
O
P
H
O
O
P
O
OH
O
H
N
O
O
O
N
O
P
O
P
O
O
O
O
Receptor
Scheme 1.
The results are close to these obtained from NMR studies and the
trend in differentiation between first and the second group of ele-
ments is well visible. Moreover, the most stable supramolecule is
established for the system formed by ligand–magnesium ion; this
finding is in accord with the results obtained so far.
O
O
O
P
H
O
Furthermore, NMR self-diffusion studies were performed for
each system at 1:1 molar ratio (Table 5). The highest difference
O
O
N
O
P
O
O
O
in
D
D (Dfree ligand ꢁ Dligand metal complexes) values was found for the
Mg2+ ions. It confirms the finding that this metal has the highest
affinity to the investigated receptor. The calculated relaxation time
T1 for free ligands revealed the higher values, than obtained for
metal–ligand systems. This is in agreement with the assumption
that correlation time sC increases and tumbling of the molecule
is slower due to enlargement of the system. Because, the diffusion
coefficient strongly depends on the molecular mass of the complex
(constant mass of L and changing mass of metals ions) therefore
the D and T1 values can not be straightforwardly related to the
roughly indicative calculated log K.
Scheme 2. The solid type arrows indicate the ester groups, which provide bigger
CIS and type dashed indicate fragments of smaller CIS (this is contractual system).
by NMR measurements appear to be in line with the theoretical
calculations (Table 4, Fig. 3). The lithium ion is bound deeper in
the binding cavity hence having {O, N} donors from both type es-
ters group, while potassium ion is bound shallower by methoxy
oxygen’s. Calculated structures of 1:1 metal to ligand complexes
of second group of elements indicate that magnesium ion might
be bound similarly to lithium ion, however less symmetrically.
The most probably the formation of the system of higher stoichi-
ometry is preferred for that ion. However, barium ion possessing
greater ionic radius and divalent charge is surrounded symmetri-
cally by {O, N} donors. The detailed calculations were performed
for all ligand–metal ion complexes and are collected in Table 4.
The observed
DD and DT1 changes are in general higher for
alkaline earth than alkali metal ions (Table 5). This result seems
to be confirmed looking at the trend of log K and b values and
ESI-MS studies, where complexes containing greater mass were
found. However, these values revealed apparent discrepancy in
relation to
of elements. The determined
plexes, where formation of polymeric species can not be excluded.
D
D values of formed complexes among the same group
D
D is extremely high for Mg2+ com-

22
P. Młynarz et al. / Journal of Molecular Structure 991 (2011) 18–23
Table 3
Roughly calculated association constants for investigated guest–host systems basing on NMR studies.
ii-Stereoisomer
iii-Stereoisomer
Log k11
Log k12
Log b12
Log k11
Log k12
Log b12
Li+
3.05 0.09
1.76 0.06
1.45 0.12
2.05 0.63
3.54 0.31
2.80 0.81
3.63 0.14
–
–
–
–
–
–
–
–
–
–
–
–
7.06
2.75 0.17
1.6 0.40
–
–
3.91 0.79
–
3.16 0.06
–
–
–
–
–
–
–
–
Na+
K+
Rb+
Mg2+
Ca2+
Ba2+
2.5 0.90
–
–
6.41
5.98 0.30*
–
3.43 0.35
Some log K12 values were not calculated for that cases where the data do not fit to the assumed model, or overlapping of signal occurred. The log K11 value was not calculated
for Cs+ ions due to small CIS value for both stereoisomers.
*
Only the cumulative constants can be calculated.
Table 4
The heat of formation
investigated metal–ligand systems.
Table 5
T1(T1 ligand ꢁ T1 comp) determined by 1H NMR method.
D
HOF = HOF (complexed) ꢁ HOF (uncomplexed) calculated for
D
D (Dligand ꢁ Dcomp) and
D
Metal ion
D
D ꢀ 10ꢁ9 (m2 sꢁ1
)
D )
T1 (sꢁ1
Isomer of (1)
Complexed cation
DHOF (kJ/mol)
Li+
0.2
0.1
0.3
0.3
0.1
0.9
0.3
0.3
0.3
0.1
0.1
0.2
0.1
0.85
0.6
0.6
RS
RS
RS
RS
RS
RS
RS
RS
Li+
ꢁ334.05
ꢁ343.20
ꢁ212.68
ꢁ212.75
ꢁ174.98
ꢁ1258.37
ꢁ1138.39
ꢁ1047.13
ꢁ316.57
ꢁ318.61
ꢁ194.15
ꢁ166.42
ꢁ152.62
ꢁ1185.88
ꢁ1096.01
ꢁ1004.74
Na+
K+
Na+
K+
Rb+
Cs+
Rb+
Cs+
Mg2+
Ca2+
Ba2+
Mg2+
Ca2+
Ba2+
RR
RR
RR
RR
RR
RR
RR
RR
Li+
Na+
K+
3.2.2. Towards organic cations
The polyglycol aminophosphonate published already did not
disclose any supramolecular properties towards organic cations
[5]. The modification of this receptor resulting in more compact
structure of polyglycol pincers significantly enhanced its binding
features.
Rb+
Cs+
Mg2+
Ca2+
Ba2+
The ESI-MS studies revealed formation of molecular complexes
formed by studied aminophosphonate with dihydrochlorides of
Lys and Arg. Moreover polyamines 2EN3A (diethylenetriamine)
and 5EN6A (pentaethylenehexaamine) acidified with formic acids
in methanol-d4 were also tested as a guest molecules (Table 6).
All of these compounds exhibited good host–guest association
properties in the gas phase. The complex of appropriate polyamine
with aminophosphonate in methanol resulted in fragmentation
processes in all cases. The exception was the 5EN6A, which was
not fragmented, most probably due to the highest affinity to the
host molecule in ESI-MS conditions.
In order to confirm the MS results NMR spectroscopy was em-
ployed. At first, the titrations in MeOD and/or CD3CN were per-
formed. In these experimental conditions the highest changes in
the chemical shift were observed both for phosphorus and proton
signals originating from of aryl and ACH2ACH2AOACH3 groups.
However, due to very small change of all parameters (chemical
shift, T1 and
DD) the obtained results did not shed the light to
the binding properties in solution. The relatively small, but not
negligible, shift is characteristic for all investigated systems but
is not sufficient for determination of association constants. The
performed relaxation T1 1H NMR measurements showed very small
deviation (0.03 s, which is in the range of experimental error)
Table 6
The main peaks (m/z) of the molecular complexes with organic cations with their
defragmentation pattern in the ESI-MS spectra at 30 V cone voltage.
Fig. 3. The examples of the calculated structures of the complexes formed between
compound 1 and: (a) Li+; (b) K+; (c) Mg2+; (d) Ba2+
.
Cation
Main peaks (m/z)
Arg
Lys
2EN3A
5EN6A
765 [L+G+H2O]+; 591 [L]+; 393 [L-PO(OR)2]+
737 [L+G]+, 591 [L]+; 393 [L-PO(OR)2]+
694 [L+G]+, 591 [L]+; 392 [L-PO(OR)2]+
823 [L+G]+
The undertaken attempts of log K2 value calculations from the
obtained curves by the used algorithm for the firs group of ele-
ments did not bring any reasonable results.

P. Młynarz et al. / Journal of Molecular Structure 991 (2011) 18–23
23
were the smallest ones in each studied group, namely Li+ and
Mg2+ ions. Similarly to metal ions also ammonium cationic of or-
ganic molecules were strongly bound to the host in the gas phase
with preferences towards pentaetylenehexamine (5EN6A). Quite
surprisingly, only moderate interactions were found in solution.
Acknowledgements
The authors would like to thank following professors: Pawel
Kafarski, Grzegorz Schroeder and Tadeusz Ossowski for stimulating
discussions and valuable remarks. The theoretical calculation were
performed in Wroclaw Center for Supercomputing and Networking
(WCSS).
Fig. 4. The calculated structures of complexes of arginine with involvement of
ammonium and guanidinium cation and oxygens originating from (O)AP, RAOAR0
entities as calculated by molecular dynamics.
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4. Conclusions
The synthesis of aminophosphonate podant containing tetragly-
col moiety provided entry into new group of promising host mol-
ecules. This ligand exhibits a very low pK of amine group which
was assigned to strong electron withdrawing properties of 2-
methoxyethyl ester units. The designed receptor exhibited differ-
ent supramolecular properties in the gas phase (ESI-MS studies)
and in solution as revealed by NMR investigation. As demon-
strated, in the gas phase all metal ions were bound to the receptor,
what was revealed by signals originating from the formed com-
plexes and by the pattern of their fragmentations. The only excep-
tion was found for Cs+, an ion of the biggest radius amongst
monovalent cations where defragmentation of the host molecule
did not occur. This is the most probably due to close intramolecular
binding. In solution, the reversed binding affinities were found. In
that case the most suitable metal ions to form supramolecules
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