Novel ammonium phosphinates containing peptide moiety: Synthesis, structure, and in vitro antimicrobial activity

Article abstract of DOI:10.2478/s11696-012-0177-8

Five new ammonium phosphinates with formula [XC₆H ₄NHC(O)NHP(O)YO]^-[H₂Y]⁺ (Y = N(CH₃)(CH₂C₆H₅), X = H (IV), CH ₃ (V), NO₂ (VI); Y = NH

Full text of DOI:10.2478/s11696-012-0177-8

Chemical Papers 66 (8) 765–771 (2012)
DOI: 10.2478/s11696-012-0177-8
ORIGINAL PAPER
Novel ammonium phosphinates containing peptide moiety:
Synthesis, structure, and in vitro antimicrobial activity
b
aKhodayar Gholivand*, Niloufar Dorosti
aDepartment of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran
bRazi Herbal Medicines Research Center, Lorestan University of Medical Sciences, P.O. Box 68149-89468, Khorramabad, Iran
Received 6 December 2011; Revised 14 February 2012; Accepted 17 February 2012
Five new ammonium phosphinates with formula [XC6H4NHC(O)NHP(O)YO]−[H2Y]+ (Y
= N(CH3)(CH2C6H5), X = H (IV ), CH3 (V ), NO2 (VI ); Y = NH(CH2C6H5), X = H
(VII ), NO2 (VIII )) were synthesised by the reaction of N-arylureidophoshoryl dichlorides with
N-methylbenzylamine or benzylamine in the presence of an excess amount of the corresponding
amine. All new compounds were characterised by NMR and IR spectral data and elemental analy-
sis. Their antimicrobial activity was tested against some Gram-positive and Gram-negative bacteria
and fungi. Compounds IV and VIII exhibited moderate activity in vitro against Bacillus subtilis.
In addition, compound VIII moderately inhibited Pseudomonas aeruginosa. The crystal structure
of benzylmethylammonium(3-phenylureido)(benzylmethylamino)phosphinate (IV ) was also deter-
mined. This compound crystallises in the orthorhombic system.
c
ꢀ 2012 Institute of Chemistry, Slovak Academy of Sciences
Keywords: ammonium phosphinate, NMR, X-ray crystallography, antimicrobial
Introduction
date, the crystal structures of many phosphorami-
dates with general formula RC(O)NHP(O)(amine)2
(e.g., R = X-C6H4, X-C6H4NH; X = F, Cl, NO2,
CH3) have been studied and anti or gauche posi-
tions have been reported for the P(O) and C(O)
groups (Gholivand et al., 2005b, 2011, 2012). On
the other hand, ammonium salts play vital biolog-
ical roles as antimicrobial agents (Dmochowska et
al., 2011), fungicides (Lukáč et al., 2009), and pes-
ticides (Nagamune et al., 2000). The synthesis and
structure of ammonium dichlorophosphate (Gholi-
vand & Pourayoubi, 2004) and pyridinium dihydro-
gen phosphate (Gholivand et al., 2007) have also
been reported, whereas ammonium phosphates bear-
ing C(O)NHP(O) moiety are rare in the relevant stud-
ies (Gholivand et al., 2005a; Yazdanbakhsh & Sab-
baghi, 2007).
The chemistry of phosphoramidates has received
considerable attention from the perspective of syn-
thesis (Asseline et al., 2003; Wan & Modro, 1996;
Ouryupin et al., 1995), stereochemistry (Zalán et
al., 2003), coordination chemistry (Gubina et al.,
2000; Trush et al., 2005), X-ray crystallography (Gho-
livand et al., 2005a, 2005b, 2005c), and theoreti-
cal studies (Gholivand et al., 2011; Gholivand &
Ghaziani, 2011). Carbacylamidophosphates (A) and
N-phosphinylureas (B) (Fig. 1) from this class have
been prepared recently, due to their biological appli-
cations as anti-cancer drugs (Gholivand et al., 2011,
2012), antimicrobial agents (Gholivand & Dorosti,
2011), and inhibitors of acetylcholinesterase (Gholi-
vand et al., 2008, 2010a) and urease (Kolc et al.,
1985). The presence of C(O)NHP(O) functionality
in these compounds not only causes diverse bio-
logical activities, but also makes different confor-
mations of P(O) versus C(O) in this skeleton. To
In the present work, as a continuation of our
research on the synthesis of N-phosphinylureas (B,
Fig. 1), five new benzylammonium phosphinates (IV–
VIII ) were prepared, structurally characterised, and
*Corresponding author, e-mail: gholi kh@modares.ac.ir

766
K. Gholivand, N. Dorosti/Chemical Papers 66 (8) 765–771 (2012)
measured. Gentamicin and clotrimazole were used as
reference antibacterial and antifungal drugs, respec-
tively. DMSO was used as a solvent control.
The minimum inhibitory concentration (MIC) val-
ues defined as the lowest concentration of the com-
pound preventing the visible growth were determined
using the microdilution broth method (Vincent &
Vincent, 1944). The test compounds dissolved in
DMSO were first diluted to the highest concentration
(2000 µg mL−1) tested. Then, serial two-fold dilutions
were made in 10 mL sterile tubes. The concentration
of cells in prepared suspensions of the standard mi-
croorganisms was in accordance with the 0.5 McFar-
land standard. A prepared suspension of the standard
microorganisms was added to each dilution in the ra-
tio of 1 : 1. Growth of the microorganisms was de-
termined visually after incubation at 35◦C for 24 h.
Gentamicin and clotrimazole were used as reference
antibacterial and antifungal drugs, respectively. Con-
trol experiments using DMSO were performed. All mi-
crodilution experiments were performed in duplicates
and repeated three times.
Fig. 1. Structures of carbacylamidophosphates (A) and
N-phosphinylureas (B).
their antimicrobial activity tested. The crystal struc-
ture of IV was also determined.
Experimental
All chemicals and solvents were purchased from
Merck and used without further purification. 1H
(500 MHz), 13C (125.76 MHz), and 31P (202.46 MHz)
NMR spectra were recorded on a Bruker Avance DRS
1
500 MHz spectrometer using TMS (for H and 13C)
as the internal standard and 85 % H3PO4 (for 31P)
as the external standard. IR spectra (in KBr pel-
lets) were obtained on a Shimadzu IR-60 spectrom-
eter. Elemental analyses were performed using a Her-
aeus CHN-O-RAPID apparatus. Melting points were
determined using an Electrothermal apparatus. X-
C6H4NHC(O)NHP(O)Cl2 (I, X = H; II, X = CH3;
III, X = NO2) were prepared according to established
methods (Papanastassiou & Bardos, 1962). All reac-
tions were carried out in argon atmosphere.
Benzylmethylammonium (3-phenylureido)
(benzylmethylamino)phosphinate (IV), benzyl-
methylammonium (3-(4-methylphenyl)ureido)
(benzylmethylamino)phosphinate (V), benzyl-
methylammonium (3-(4-nitrophenyl)ureido)
(benzylmethylamino)phosphinate (VI), benzyl-
ammonium (3-phenylureido)(benzylamino)
phosphinate (VII), and benzylammonium (3-
(4-nitrophenyl)ureido)(benzylamino)
X-ray data were collected on a Bruker SMART
1000 CCD single crystal diffractometer with graphite-
˚
monochromated (Mo Kα = 0.71073 A) radiation. The
phosphinate (VIII)
structures were refined with SHELXTL (Sheldrick,
1998a) by full-matrix least-squares on F2. The po-
sitions of hydrogen atoms were obtained from the dif-
ference Fourier map. Routine Lorentz and polarisation
corrections were applied and an absorption correction
was performed for compounds using the SADABS pro-
gram (Sheldrick, 1998b).
Compounds IV–VIII were synthesised by a gen-
eral method as follows: a solution of the correspond-
ing amine (5.2 mmol) (methylbenzylamine for IV–VI;
benzylamine for VII and VIII ) in acetonitrile (30 mL)
was added dropwise to a solution of the corresponding
phosphoramidic dichloride (1.3 mmol) (I for IV; II for
V; III for VI )) in acetonitrile at 0◦C and the reaction
mixture was stirred for 4 h. The precipitated white
solid was filtered and the crude product (IV–VIII )
was washed with water and dried.
The cup-plate agar method (Barry, 1976) was used
to determine the antibacterial activity of compounds
IV–VIII against two Gram-positive bacteria (Bacil-
lus subtilis (ATCC 6633) and Staphylococcus aureus
(ATCC 6538P)) and two Gram-negative bacteria (Es-
cherichia coli (ATCC 35218) and Pseudomonas aerug-
inosa (ATCC 9027)) as well as two fungi (Aspergillus
niger (ATCC 16404) and Candida albicans (ATCC
10218)). Base plates were prepared by pouring an au-
toclaved Mueller–Hinton (MH) agar (for bacteria) and
Sabouraud dextrose agar (for fungi) into sterile Petri
dishes and allowing them to settle. The solutions (c =
2000 µg mL−1) of compounds in dimethyl sulphoxide
(DMSO) were used. Then, the solutions of the com-
pound tested were transferred onto wells filled with
the media inoculated with the microorganisms. The
plates were incubated at 35◦C for 24 h and the diam-
eters of growth-inhibition zones around the discs were
Results and discussion
The reaction of amines with phosphoramidic dichlo-
rides in the presence of the HCl scavenger is a method
for the formation of phosphoramidates. Some of these
compounds with P(O)[N(X)(CH2C6H5)]2 moiety (X
= H, CH3, CH2C6H5) were previously synthesised by
the reaction of phosphoramidic dichlorides with ben-
zylamine, methylbenzylamine, and dibenzylamine in
the presence of the HCl scavenger (Gholivand et al.,
2005b; Dehghanpour et al., 2010). Using similar re-
action conditions, ammonium phosphinates IV–VIII
were obtained in the present work, probably as a

K. Gholivand, N. Dorosti/Chemical Papers 66 (8) 765–771 (2012)
767
Fig. 2. Synthesis pathway for compounds IV–VIII. Reaction conditions: i) CH3CN, 0◦C, 4 h; for R and R1, see Table 1.
Table 1. Characterisation data of newly prepared compounds
wi(calc.)/mass %
wi(found)/mass %
Yield
M.p.
Compound
R
R1
Formula
Mr
C
H
N
%
50
80
80
40
50
◦C
IV
V
H
CH3
CH3
CH3
H
C23H29N4O3P
C24H31N4O3P
C23H28N5O5P
C21H25N4O3P
C21H24N5O5P
440.48
454.51
485.48
412.43
457.42
62.72
62.81
63.28
63.35
56.90
56.82
61.16
61.08
55.14
55.09
6.64
6.57
6.86
6.80
5.81
5.90
6.11
6.22
5.29
5.21
12.72
12.69
12.30
12.25
14.42
14.51
13.58
13.61
15.31
15.38
140–141
159–160
151–152
145–146
155–156
CH3
NO2
H
VI
VII
VIII
NO2
H
consequence of hydrolysis of starting phosphoramidic
dichlorides to intermediates I–III in the course of the
reaction (Fig. 2). Their characterisation and spectral
data are summarised in Tables 1 and 2.
1
The H NMR spectra of compounds IV–VIII dis-
3
play a doublet at δ 3.98–4.09 with J(P,NCH) cou-
pling constants in the range of 6.9–9.8 Hz which
is attributed to the methylene group in the benzy-
lamine moiety. In addition, two other different signals
are observed for CH3 groups in compounds IV–VI.
One of them exhibits coupling with phosphorus atom
(3J(P,NCH) approximately 9.8 Hz; this is higher than
3
the J(P,NCH) value for methylene groups). The low-
field signals of NH2+ (for IV–VI ) and NH+3 (for VII,
VIII ) protons are observed in the range of δ 8.28–
11.89. In the 13C NMR spectra, four signals are ob-
served for each of the methyl and methylene groups
in compounds IV–VI. Derivatives VII and VIII show
two distinct peaks of methylene carbon atoms.
Colourless crystals of IV suitable for X-ray diffrac-
tion analysis were obtained from chloroform/heptane.
The crystal data and details of the X-ray analysis are
given in Table 3, selected bond lengths and angles in
Table 4.
Fig. 3. Molecular structure of IV showing hydrogen bond in-
teractions.
molecular hydrogen bond (Fig. 3). The formation of
centre-symmetric dimers is observed in the crystalline
state. This cyclic eight-member pattern is formed
through N(2)—H(2N)· · ·O(3) hydrogen bonds by two
anions. Moreover, the anion is connected with two
cations via the intermolecular hydrogen bonds N(4)—
H(4NB)· · ·O(1) and N(4)—H(4NA)· · ·O(2). Thus, the
The crystal structure of compound IV consists of
a phosphoric diamide anion and a methylbenzylam-
monium cation linked via O(1)· · ·H(4)—N(4) inter-

768
K. Gholivand, N. Dorosti/Chemical Papers 66 (8) 765–771 (2012)
Table 2. Spectral data of newly prepared compounds
Compound Spectral data
+
IR, ν˜/cm−1: 3360 (NH), 3200 (NH2 ), 3035, 1686 (C O), 1597, 1540, 1491, 1451, 1307, 1212, 1175 (P O), 1050,
—
—
—
—
IV
909, 746, 689, 599, 506
3
3
1H NMR (DMSO-d6), δ: 2.32 (d, 3H, J(P,NCH) = 9.4 Hz, CH3), 2.49 (s, 3H, CH3), 3.98 (d, 2H, J(P,NCH)
=
2
3
6.9 Hz, CH2), 4.09 (s, 2H, CH2), 6.20 (d, 1H, J(P,NH) = 2.7 Hz, NHP), 6.86 (t, 1H, J(H,H) = 7.3 Hz), 7.21 (m,
7H), 7.32 (d, 2H, J(H,H) = 7.4 Hz), 7.37 (m, 3H), 7.40 (d, 2H, J(H,H) = 1.7 Hz), 8.28 (bs, 2H, NH+2 ), 10.89 (s,
3
3
1H, NHPh)
2
13C NMR (DMSO-d6), δ: 32.2, 33.9 (d, J(P,C) = 2.7 Hz), 51.4, 53.3, 117.8, 120.9, 126.3, 127.7, 127.9, 128.6 (d,
3J(P,C) = 5.4 Hz), 128.8, 129.7, 132.3, 140.5, 140.6, 154.9
3
2
31P NMR (DMSO-d6), δ: –1.69 (m, J(P,NCH) = 9.4 Hz and 6.9 Hz, J(P,NH) = 2.7 Hz)
+
IR, ν˜/cm−1: 3174 (NH), 3150 (NH2 ), 2849, 1671 (C O), 1602, 1553, 1513, 1454, 1402, 1327, 1252, 1191 (P O),
—
—
—
—
V
1048, 1001, 956, 911, 854, 819, 771, 727, 697, 575, 558, 520, 464
3
1H NMR (DMSO-d6), δ: 2.19 (s, 3H, CH3), 2.33 (d, 3H, J(P,NCH) = 10.0 Hz, CH3), 2.47 (s, 3H, CH3), 3.98 (d,
3
2
2H, J(P,NCH) = 7.1 Hz, CH2), 4.06 (s, 2H, CH2), 6.42 (d, 1H, J(P,NH) = 2.7 Hz and 2.8 Hz, NHP), 7.00 (d, 2H,
3J(H,H) = 8.3 Hz), 7.18 (t, 1H, J(H,H) = 7.0 Hz), 7.26 (m, 6H), 7.37 (m, 3H), 7.48 (m, 2H), 9.15 (bs, 2H, NH+2 ),
3
10.78 (s, 1H, NHPh)
2
2
13C NMR (DMSO-d6), δ: 20.3, 32.2, 33.9 (d, J(P,C) = 2.8 Hz), 51.4, 53.3 (d, J(P,C) = 2.3 Hz), 117.9, 126.3, 127.8,
3
127.9, 128.6, 128.8, 129.0, 129.6, 129.7, 132.6, 137.9, 140.6 (d, J(P,C) = 6.5 Hz), 154.9
3
2
31P NMR (DMSO-d6), δ: 0.15 (m, J(P,NCH) = 10.0 Hz and 6.9 Hz, J(P,NH) = 2.3 Hz and 2.8 Hz)
+
—
—
VI
IR, ν˜/cm−1: 3263 (NH), 3205 (NH2 ), 3064, 2907, 2805, 1698 (C O), 1595, 1554, 1495, 1302, 1226, 1225, 1191
—
—
(P O), 1112, 1057, 1017, 953, 903, 855, 814, 750, 726, 696, 651, 594, 540, 522, 474
1H NMR (DMSO-d6), δ: 2.34 (d, 3H, J(P,NCH) = 10.0 Hz, CH3), 2.48 (s, 3H, CH3), 4.00 (d, 2H, J(P,NCH)
7.2 Hz, CH2), 4.08 (s, 2H, CH2), 7.05 (d, 1H, J(P,NH) = 3.0 Hz, NHP), 7.17 (t, 1H, J(H,H) = 7.0 Hz), 7.27 (m,
4H), 7.38 (m, 3H), 7.49 (m, 2H), 7.60 (d, 2H, J(H,H) = 9.2 Hz), 8.11 (d, 2H, J(H,H) = 9.2 Hz), 9.17 (bs, 2H,
3
3
=
2
3
3
3
NH+2 ), 11.89 (s, 1H, NHPh)
2
2
13C NMR (DMSO-d6), δ: 32.1, 33.8 (d, J(P,C) = 3.0 Hz), 51.3, 53.2 (d, J(P,C) = 2.5 Hz), 117.1, 125.2, 126.4,
127.7, 127.9, 128.6, 128.8, 129.8, 132.2, 140.4, 147.1, 154.6
3
2
31P NMR (DMSO-d6), δ: –0.14 (m, J(P,NCH) = 10.0 Hz and 7.2 Hz, J(P,NH) = 3.0 Hz)
+
IR, ν˜/cm−1: 3360 (NH), 3200 (NH3 ), 3035, 1686 (C O), 1597, 1540, 1491, 1451, 1307, 1212, 1175 (P O), 1050,
—
—
—
—
VII
909, 746, 689, 599, 506
3
2
1H NMR (DMSO-d6), δ: 2.33 (d, 2H, J(P,NCH) = 9.6 Hz, CH2), 3.98 (d, 2H, J(P,NH) = 6.2 Hz, NH), 4.08 (s, 2H,
3
3
CH2), 6.43 (s, 1H, NHP), 6.86 (t, 1H, J(H,H) = 6.9 Hz), 7.19 (t, 3H, J(H,H) = 7.4 Hz), 7.26 (m, 4H), 7.37 (d, 5H,
3J(H,H) = 9.4 Hz), 7.48 (s, 2H), 9.13 (bs, 3H, NH+3 ), 10.94 (s, 1H, NHPh)
13C NMR (DMSO-d6), δ: 51.4, 53.3, 117.8, 120.9, 126.3, 127.7, 127.9, 128.6 (d, J(P,C) = 5.4 Hz), 128.8, 129.7,
3
3
132.3, 140.5 (d, J(P,C) = 9.5 Hz), 154.9
3
31P NMR (DMSO-d6), δ: –1.36 (d, J(P,NCH) = 9.6 Hz)
+
—
—
VIII
IR, ν˜/cm−1: 3396 (NH), 3287 (NH3 ), 2911, 1692 (C O), 1604, 1537, 1503, 1473, 1408, 1340, 1305, 1264, 1210,
—
—
1177 (P O), 1112, 1041, 911, 856, 745, 697, 653, 525, 501
1H NMR (DMSO-d6), δ: 3.90 (bs, 1H, NH), 3.92 (d, 2H, J(P,NCH) = 9.8 Hz, CH2), 3.98 (s, 2H, CH2), 6.97 (bs,
1H, NHP), 7.14 (t, 2H, J(H,H) = 7.2 Hz), 7.17 (t, 2H, J(H,H) = 7.7 Hz), 7.33 (m, 4H), 7.62 (d, 2H, J(H,H)
3
3
3
3
=
9.3 Hz), 8.07 (d, 2H, J(H,H) = 9.4 Hz), 8.15 (d, 2H, J(H,H) = 9.3 Hz), 8.48 (s, 1H, NHPh), 11.73 (bs, 3H, NH3+
)
3
3
13C NMR (DMSO-d6), δ: 42.3, 45.4, 117.1, 125.1, 126.0, 127.1, 127.8, 128.3, 128.6, 128.8, 134.4, 140.3, 142.5 (d,
3J(P,C) = 7.0 Hz), 147.1, 154.4
3
31P NMR (DMSO-d6), δ: –1.69 (d, J(P,NCH) = 9.8 Hz)
˚
—
A (for P(1) O(2)) that are higher than the normal
—
whole packing structure results in the two-dimensional
polymeric chain shown in Fig. 3. There is also the
˚
O bond length (1.450 A) (Corbridge, 1995). The
—
P
—
—
intra-molecular P O· · ·H—NPh hydrogen bond in
nitrogen atoms are also distorted from planarity. The
sums of the angles around these atoms are 354.65◦,
351.86◦, and 359.36◦ for N(1), N(2), and N(3) atoms,
respectively. In addition, the nitrogen atom in the
methylbenzylammonium cation has a slightly dis-
torted tetrahedral configuration with the bond angles
in the range of 97.3–118.5◦.
—
phosphoric diamide ion which does not cause a change
in the network of the crystal. The crystal structure
of compound IV shows two different dihedral an-
gles for O—P—C—O bonds. The torsion angles of
O(1)P(1)C(1)O(3) and O(2)P(1)C(1)O(3) are approx-
imately –74.65◦ and 166.59◦, respectively.
The phosphorus atom has a slightly distorted
tetrahedral configuration with the bond angles in
the range from 104.06(11)◦ [N(1)—P(1)—N(2)] to
The assay of the bacteria inhibition measurement
showed that compounds IV–VIII were completely in-
active against E. coli, S. aureus, A. niger, and C.
albicans, whereas their moderate activity against B.
subtilis and P. aeruginosa was observed (Table 5).
118.13(11)◦ [O(1)—P(1)—O(2)]. The P O bond
—
—
˚
—
—
lengths are 1.488(18) A (for P(1) O(1)) and 1.497(18)

K. Gholivand, N. Dorosti/Chemical Papers 66 (8) 765–771 (2012)
Table 3. Crystallographic data and structure refinement for compound IVa
769
Empirical formula
C23H29N4O3P
Formula mass
440.47
Temperature, T/K
120(2)
˚
Wavelength, λ/A
0.71073
Crystal system, space group
˚
a/A
Orthorhombic, Pbca
19.326(6)
˚
b/A
8.314(3)
˚
c/A
Unit-cell volume, V/A
Formula per unit cell, Z
28.625(12)
4654(3)
8
1.257
0.149
1872
3
˚
Density, Dcalc/(g cm−3
Absorption coefficient, µ/mm−1
F(000)
)
Crystal size/mm
0.21 × 0.18 × 0.15
θ range for data collection/◦
Index ranges
1.77–28.37
–25 ≤ h ≤ 25
–11 ≤ k ≤ 11
–38 ≤ l ≤ 38
45872
Reflections collected
Independent reflections (Rint
Completeness to θ/%
)
5810 (0.0893)
99.6
Maximum and minimum transmission
Refinement method
Data/restraints/parameters
Goodness-of-fit on F 2
0.8621 and 0.7488
Full-matrix least-squares on F 2
5810/0/282
1.011
R indices [I > 2σ(I)]
R indices (all data)
Largest difference peak and hole/(e A
R1 = 0.0508, wR2 = 0.1126
R1 = 0.1101, wR2 = 0.1508
0.422 and –0.612
−3
˚
)
a) Standard deviations in parentheses.
◦
a
˚
Table 4. Selected bond lengths (A) and angles ( ) for compound IV
Bond length
Bond angle
Bond angle
Bond angle
Bond
Bond
Bond
Bond
◦
◦
◦
˚
A
P(1)—N(1) 1.635(2) O(1)—P(1)—O(2) 118.13(11)
P(1)—N(2) 1.701(2) O(1)—P(1)—N(1) 108.62(11)
P(1)—O(1) 1.4885(18) O(2)—P(1)—N(1) 110.96(11) C(17)—N(4)—C(16) 111.84(19) C(16)—N(4)—H(4NB)
O(2)—P(1)—N(2)
N(1)—P(1)—N(2)
105.41(10) C(16)—N(4)—H(4NA)
104.06(11) C(17)—N(4)—H(4NB)
97.3
109.6
105.8
112.6
P(1)—O(2) 1.4966(18) O(1)—P(1)—N(2) 108.68(10) C(17)—N(4)—H(4NA)
118.5
H(4NA)—N(4)—H(4NB)
a) Standard deviations in parentheses.
Table 5. Antibacterial activity (GIZ and MIC)a of compounds IV–VIII
Bacillus subtilis
Pseudomonas aeruginosa
GIZ/mm )
MIC/(µg mL−1
Compound
GIZ/mm
MIC/(µg mL−1
)
IV
V
VI
VII
VIII
11
11
13
11
11
23
860
>1000
>1000
>1000
865
12
11
11
11
12
20
>1000
>1000
>1000
>1000
670
Gentamicin
6.25
1.5
a) The values indicate the diameters in mm of the zone of growth inhibition (GIZ) and minimum inhibitory concentration (MIC)
observed after 24 h of incubation at 35◦C. Error values are within
1 mm.
Compounds IV and VIII exhibited an effective an-
timicrobial activity against B. subtilis, but only VIII
was active against P. aeruginosa. The activity of IV–
VIII was lower than that of gentamicin. The present
findings indicate that the in vitro activity of these
compounds against both Gram-positive and Gram-

770
K. Gholivand, N. Dorosti/Chemical Papers 66 (8) 765–771 (2012)
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Fig. 4. A two-dimensional polymer chain produced by hydro-
gen bonds in the crystalline lattice of IV.
negative bacteria varied unpredictably. This is prob-
ably due to the differing abilities of these compounds
to cross the cell wall of Gram-positive and Gram-
negative bacteria.
Conclusions
Five new benzylammonium phosphinates were syn-
thesised. Their NMR spectra exhibited the presence
of an ion pair, as confirmed by X-ray crystallography
of compound IV. Evaluation of the biological activ-
ity revealed that only two compounds (IV and VIII )
were moderately active against Bacillus subtilis and
only IV was moderately active against Pseudomonas
aeruginosa. Compounds IV–VIII are completely inac-
tive against E. coli, S. aureus, A. niger, and C. albi-
cans.
Acknowledgements. The financial support of this work pro-
vided by the Research Council of Tarbiat Modares University
and the Razi Herbal Medicines Research Centre of Lorestan
University of Medical Sciences are gratefully acknowledged.
The authors wish to thank Dr. Bahram Rasoulian in the Razi
Herbal Medicines Research Centre of Lorestan for his assis-
tance.
Gholivand, K.,
& Ghaziani, F. (2011). Synthesis, spectro-
scopic and configurational study, and ab initio calculations of
new diazaphospholanes. Chemical Papers, 65, 691–699. DOI:
10.2478/s11696-011-0047-9.
Gholivand, K., Hosseini, Z., Farshadian, S., & Naderi-Manesh,
H. (2010a). Synthesis, characterization, oxidative degrada-
tion, antibacterial activity and acetylcholinesterase/butyryl
cholinesterase inhibitory effects of some new phosphorus(V)
hydrazides. European Journal of Medicinal Chemistry, 45,
5130–5139. DOI: 10.1016/j.ejmech.2010.08.025.
Supplementary data
Crystallographic data for structure IV have been de-
posited with the Cambridge Crystallographic Data Cen-
tre as supplementary publication Nos. CCDC 786394
(C23H29N4O3P). Copies of the data may be obtained free
of charge upon request from CCDC, 12 Union Road, Cam-
bridge CB2 1EZ, UK, (fax: +44 1223 336033; E-mail:
deposit@ccdc.cam.ac.uk or www: http://www.ccdc.cam.ac.
uk).
Gholivand, K., Mostaanzadeh, H., Koval, T., Dusek, M., Erben,
M. F., Stoeckli-Evans, H., & Della Védova, C. O. (2010b).
Syntheses, spectroscopic study and X-ray crystallography of
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