Molecular structure, vibrational spectra and quantum mechanical force fields of modified oligonucleotide linkages: 1. Methyl methoxymethanphosphonate

Article abstract of DOI:10.1016/S0022-2860(97)00079-3

Methyl methoxymethanphosphonate (CH₃OCH₂P(O₂)OCH₃/^-) (MMP) was studied by vibrational spectroscopy and by ab initio calculations. IR and Raman spectra were measured from 1 M aqueous solutions and crystalline samples of sodium and potassium salts of MMP. In these spectra, a superimposition of the counter-ion and conformational effects was observed. The observed spectra were interpreted by Using the Hartree-Fock (HF) and double harmonic approximations and the 6-31G* set of atomic orbitals. The full gradient optimization and vibrational analysis of the g^-gg and g^-gt conformations of MMP in the anionic forms and also completed with the Na⁺ and K⁺ ions were carried out. The harmonic frequencies and IR and Raman intensities were predicted by using the scale factors for the HF/6-31G* force field that were transferred from the dimethyl phosphate union (DMP) and its sodium salt. The good agreement between the experimental and calculated spectra in the 2001800 cm^-1 frequency region evidenced the transferability of scale factors between DMPT and MMP and also between compounds completed with different metal ions.

Full text of DOI:10.1016/S0022-2860(97)00079-3

MOLSTR 9830
Journal of Molecular Structure 415 (1997) 161–177
Molecular structure, vibrational spectra and quantum mechanical
force fields of modified oligonucleotide linkages:
1. methyl methoxymethanphosphonate
a
a
a,b
ˇ
Marek Strajbl , Vladimı´r Baumruk , Jan Floria´n ,
c
c
a
ˇ
Lucie Bedna´rˇova´ , Ivan Rosenberg , Josef Steˇpa´nek
aInstitute of Physics, Charles University, Ke Karlovu 5, 12116 Prague 2, Czech Republic
bDepartment of Chemistry, University of Southern California, Los Angeles, CA 90089-1062, USA
cInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo na´m. 2, CZ-16610 Prague 6,
Czech Republic
Received 7 October 1996; accepted 15 February 1997
Abstract
Methyl methoxymethanphosphonate (CH3OCH2P(O2)OCH−3) (MMP) was studied by vibrational spectroscopy and by
ab initio calculations. IR and Raman spectra were measured from 1 M aqueous solutions and crystalline samples of sodium
and potassium salts of MMP. In these spectra, a superimposition of the counter-ion and conformational effects was observed.
The observed spectra were interpreted by using the Hartree–Fock (HF) and double harmonic approximations and the 6-31G*
set of atomic orbitals. The full gradient optimization and vibrational analysis of the g−gg and g−gt conformations of MMP in the
anionic forms and also completed with the Na+ and K+ ions were carried out. The harmonic frequencies and IR and Raman
intensities were predicted by using the scale factors for the HF/6-31G* force field that were transferred from the dimethyl
phosphate anion (DMP) and its sodium salt. The good agreement between the experimental and calculated spectra in the 200–
1800 cm−1 frequency region evidenced the transferability of scale factors between DMPT and MMP and also between
compounds completed with different metal ions. ᭧ 1997 Elsevier Science B.V.
Keywords: Vibrational spectroscopy; Ab initio calculations; Force field; Conformational isomerism; Methyl methoxymethan-
phosphate
1. Introduction
the phosphodiester bond [1,2]. Such properties are
of general importance for the development of anti-
sense drugs [3–5]. Typically, anti-sense drugs are
designed as modified oligonucleotides that enter
infected cells and bind to target sequences of
mRNA that code hostile enzymes. Here, the modi-
fications can range from methyl phosphonates,
phosphoroamidates and phosphorothiothates to entire
The methyl methoxymethanphosphonate (MMP)
molecule (Fig. 1) serves as the smallest realistic
model of the phosphodiester internucleotide junction
modified by inserting the –CH2– group. This modi-
fication was shown to be capable of enhancing
stability toward enzymes catalysing hydrolysis of
0022-2860/97/$17.00 Copyright ᭧ 1997 Elsevier Science B.V. All rights reserved
PII S0022-2860(97)00079-3

ˇ
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
162
Fig. 1. Top: numbering of methyl methoxymethanphosphonate (MMP). In the text, the O1 and O2 atoms are also denoted as O* and O3 and O4
atoms as O. Middle and Bottom: stereo views of the g−gg and g−gt conformers of KMMP, respectively.
replacement of the deoxyribose–phosphate linkage
[6–9]. In a different but equally promising theme,
phosphonate esters are being used as templates in
the design of novel enzymes from monoclonal
antibodies [10]. In this approach, the similarity of
phosphonate esters to transition-state structures of
several biologically important chemical reactions is
utilized [11].
Vibrational spectra of anionic phosphonate esters
have been little studied. For neutral organophosphorus
compounds that contain PC bonds, IR spectra have
been reported for solid state and solutions [12] and
also for gaseous molecules [13]. For salts of phos-
phorus ions, including salts of phosphonate alkyl
esters, compilation of IR data was published by
Thomas and Chittenden [14]. However, no IR spectra
from aqueous solutions or Raman spectra from
phosphonate esters have been reported.
incorporated into standard B- and A-forms of DNA
and RNA double helices without perturbing their
secondary structures. In this paper, we present IR
and Raman spectra of the Na+ and K+ salts of MMP,
measured from aqueous solutions and solids. In order
to find out whether the oligonucleotides modified by
the insertion of the methylene group could be spectro-
scopically distinguished from the native oligonucleo-
tides we compared the spectra of MMP with the
spectra of dimethyl phosphate published previously
[16–18]. Measured data were interpreted by using the
Scaled Quantum Mechanical [19] (SQM) HF/6-31G*
force field calculated for two distinct conformers of
MMP. The scale factors for this force field were trans-
ferred from the sodium salt of dimethyl phosphate [18].
In other words, our computational methodology does
not make use of any experimental data from MMP.
Consequently, the agreement between the calculated
and experimental spectra can serve as a test of the
universal applicability of our set of scale factors to the
family of organophosphorus compounds.
In the previous ab initio study [15] we examined
the gas-phase conformational flexibility of the
MMP anion. Also, we showed that MMP can be

ˇ
163
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
Fig. 2. Preparation of samples of MMP.
2. Experimental
twice with methanol–ether and finally with ether.
Drying in vacuo (13 Pa) over phosphorus pentoxide
afforded compound 4 as an amorphous white solid
(6.4 g).For C3H8O4P.6/5Na (139.06) calculated:
21.62% C, 4.84% H, 18.59% P; found: 21.63% C,
4.89% H, 18.88%P.1H NMR spectrum (200 MHz) in
deuterium oxide: 3.43 d, 3 H, J(CH3OCP) = 0.9; 3.60
d, 3 H, J(CH3OP) = 10; 3.64 d, 2 H, J(CH2P) = 8.5.
2.1. Preparation of samples (Fig. 2)
2.1.1. Dimethyl methoxymethanphosphonate (3)
Chloromethyl methyl ether (2) (8 mL, 105 mmol)
was added drop-wise, at 80ЊC, to vigorously stirred
trimethyl phosphite (1) (11.8 mL, 100 mmol) for 1 h
with exclusion of moisture. The resulting mixture was
heated at 100ЊC for 6 h and then distilled in vacuo to
afford dimethylmethoxymethanphosphonate (3)
(11 g, 71%, b.p. 70ЊC/2 kPa). For C4H11O4P (154.1)
calculated: 31.18% C, 7.19% H, 20.10% P; found:
31.13% C, 7.14% H, 19.95% P. Mass spectrum
(FAB): 155.5 (M+ + H).
2.2. Raman spectroscopy
Raman spectra were excited with the 488 nm line of
an argon laser using approximately 200 mW of
radiant power at the sample. Spectra of the poly-
crystalline sodium and potassium salts of MMP in
the 150–3100 cm−1 spectral region were collected
on a single channel spectrometer at 1 cm−1 intervals
with an integration time of 6 s, using a spectral slit
width of 3 cm−1. Spectra of 1.0 M solutions of both
MMP salts were recorded on a multichannel Raman
spectrometer with a CCD detection system having
1024 pixels along the dispersion axis, and collected
in the 350–1750 cm−1 and 2200–3500 cm−1 intervals
with a 6 cm−1 spectral slit-width and an accumulation
time of 200 s. The spectral frequencies were cali-
brated with argon-ion laser plasma lines and are
believed to be accurate to Ϯ 1 cm−1. For collection
of the parallel and perpendicular components of the
polarized Raman spectra of solution samples, a plane
of polarization of the incident beam was rotated and
the orientation of a polarizing analyzer located
between the sample and the entrance slit of the
spectrograph was kept fixed. The solvent spectrum
in the O–H stretching region was carefully subtracted.
Peak positions were determined by a curvefit
procedure using a SpectraCalc software.
2.1.2. Methyl methoxymethanphosphonate, sodium
salt (4)
A solution of dimethylmethoxymethanphosphonate
(3) (7 g, 45.4 mmol) in pyridine–water (3:2, 50 mL)
was heated for 10 h at 70ЊC. Thin-layer chromato-
graphy on silica gel plates with chloroform–ethanol
(9:1) as mobile phase, followed by detection with
4-(4-nitrobenzyl)pyridine solution [20], revealed
quantitative disappearance of the starting material 3
during this time. The solution was passed through the
column of Dowex 50 in the pyridinium form (100 mL)
to remove the N-methylpyridinium cation. The
column was washed with two volumes of pyridine–
water (3:2), and the combined eluate was evaporated
with triethylamine (3 mL) under reduced pressure. An
oily residue was co-evaporated several times with
ethanol (50 mL) to remove of traces of pyridine,
dissolved in water (50 mL), and converted to the
sodium salt through the Dowex 50 resin (Na+ form)
(100 mL). The compound was eluted with water (two
column-volumes) and the combined eluate was
evaporated under reduced pressure. The residue was
co-evaporated twice with ethanol, suspended in
methanol–ether (7:3, 100 mL) and sonicated for
20 min. The white solid was filtered off, washed
2.3. Infrared spectroscopy
Infrared spectra of solid sodium and potassium
MMP salt in KBr pellets were recorded with a Nicolet

ˇ
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
164
Table 1
Definition of the internal coordinates of MMP
Coordinatea
Description
Definitionb
nPO1
nPO3
nPC
PO* stretching
PO stretching
PC stretching
DrP,O1
DrP,O3
DrP,C
nPNa
PNa stretching
DrP,Na
nCO4
nOC3
nCHs
nCHa
nC3Hs
nC3Ha1
nC3Ha2
dCOP
dPNa1
dPNa2
dPOr
dPOw
dPOt
dCHs
dCHr
dCHw
dCHt
dOCP
dC3Hs
CO4 stretching
DrC,O4
DrO3,C3
DrC,H1 + DrC,H2
DrC,H1 − DrC,H2
DrC3,H31 + DrC,H32 + DrC3,H33
2DrC3,H31 − DrC3,H32 − DrC3,H33
DrC3,H32 − DrC3,H33
DaC3,O3,P
DaNa,P,O1 − DaNa,P,O2
O3C3 stretching
CH sym. stretching
CH asym stretching
CH3 sym. stretching
CH3 asym. stretching
C3O3P bending
O*PNa bending
OPNa bending
PO2* rocking
PO2* wagging
PO2* twisting
CH2 sym. bending
CH2 rocking
DaNa,P,O3 − DaNa,P,C
DaO1,P,C − DaO2,P,C + DaO1,P,O3 − DaO2,P,O3
DaO1,P,C + DaO2,P,C − DaO1,O,O3 − DaO2,P,O3
DaO1,P,C − DaO2,P,C − DaO1,P,O3 + DaO2,P,O3
DaH1,C,H2
DaH1,C,P − DaH2,C,P + DaH1,C,O4 − DaH2,C,O4
DaH1,C,P + DaH2,C,P − DaH1,C,O4 − DaH2,C,O4
DaH1,C,P − DaH2,C,P − DaH1,C,O4 + DaH2,C,O4
DaO4,C,P
CH2 wagging
CH2 twisting
OCP bending
CH3 sym. bending
DaH31,C3,H32 + DaH32,C3,H33 + DaH33,C3,H31
DaO3,C3,H31 − DaO3,C3,H32 − DaO3,C3,H33
−
dC3Ha1
dC3Ha2
dC3Hr1
dC3Hr2
tC3O3
tC4O4
tPO3
CH3 asym. bending
CH3 rocking
2DaH31,C3,H32 − DaH32,C3,H33 − DaH33,C3,H31
DaH32,C3,H33 − DaH33,C3,H31
2aO3,C3,H31 − DaO3,C3,H32 − DaO3,C3,H33
DaO3,C3,H32 − DaO3,C3,H33
C3O3 torsion
C4O4 torsion
PO3 torsion
PC torsion
13(DtH31,C3,O3,P + DtH32,C3,O3,P + DtH33,C3,O3,P
)
13(DtH41,C4,O4,C + DtH42,C4,O4,C + DtH43,C4,O4,C
)
13(DtC,P,O3,C3 + DtO1,P,O3,C3 + DtO2,P,O3,C3
13(DtO1,P,C,O4 + DtO2,P,C,O4 + DtO3,P,C,O4
13(DtH1,C,O4,C4 + DtH2,C,O4,C4 + DtP,C,O4,C4
)
)
tPC
tCO4
)
CO4 torsion
aCoordinates observing local symmetry. Only coordinates for the structurally unique part of the molecule are given. The definition of internal
for other parts of the molecule was done analogously.
bThe symbols r, a and t denote bond length, bond angle, and torsional angle, respectively. For atom numbering see Fig. 1.
Impact 400 FTIR spectrometer. Spectra in the region
from 400 cm−1 to 4000 cm−1 were collected with a
standard source, a KBr beam splitter and a DTGS
detector. Spectra of 1.0 M solutions of both MMP
salts in H2O were measured in a demountable cell
(Graseby Specac) consisting of a pair of CaF2
windows separated by a 6 mm Mylar spacer. The
solvent spectrum was carefully subtracted. Generally,
512 scans were collected with a spectral resolution of
2 cm−1 and Happ–Genzel apodization function.
Mylar beam-splitter and a DTGS detector. Generally,
512 scans were collected with a spectral resolution of
2 cm−1 and Blackmann–Harris 3-term apodization
function.
No baseline corrections were made. Absorption
peak positions were determined by a curvefit
procedure using a SpectraCalc software.
2.4. Computational methods
Spectra in the far IR region from 80 cm−1 to
550 cm−1 were measured in CsI pellets on a Bruker
IFS-88 spectrometer with a standard source, a 6 mm
The geometry of MMP was calculated by using the
Hartree–Fock (HF) approximation. The Wachter’s
Gaussian basis set of the DZP quality [21] was used

ˇ
165
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
for potassium, whereas the standard 6-31G* polarized
split-valence basis set was used for other atoms. To
assess the influence of the polar environment on the
relative stability of different conformers we carried
out PCM calculations [22,23]. In these calculations
a molecule is put into a cavity in an infinite polariz-
able continuum. The cavity is shaped as the inter-
section of Van der Waals spheres of individual
atoms that form the molecule. We used Bondi’s set
of Van der Waals radii [24] for C, H, O, P and Na+.
For K+, the Van der Waals radius of 1.98 was used.
These radii were scaled by a factor of 1.2. Calcula-
tions were carried out using the gaussian 92 [25] and
gaussian 94 [26] programs.
The normal modes, vibrational frequencies, IR
intensities, and Raman-scattering activities were
calculated from HF/6-31G* force-constants matrices
and atomic polar tensors and Cartesian polarizability
derivatives using harmonic approximation [27,28].
For spectral interpretation the Cartesian force-
constant matrix was transformed into standard
internal coordinates observing local symmetry
(Table 1) and scaled by scale-factors transferred
from dimethyl phosphate and sodium dimethyl
phosphate. MMP diagonal force constants were scaled
by seven independent scale factors developed for HF/
6-31G* harmonic force field of DMP, diagonal force
constants of NaMMP and KMMP were scaled by 11
independent scale factors developed for HF/6-31G*
harmonic force field of NaDMP [18]. The scale
factors for interaction force constants were calculated
with respect to the jth normal coordinate [31,32]. In
this paper, Raman differential cross-sections were
evaluated for the temperature 300 K and the excita-
tion wavelength 488 nm. The calculated spectra were
plotted as a sum of Gaussian curves with a half-width
of 10 cm−1
3. Results and discussion
3.1. Geometry of MMP and its sodium and potassium
salts
As revealed by our gas-phase ab initio study [15],
the potential energy surface of the MMP anion con-
tains seven minima that can be characterized by the
approximate values of the torsional angles z, a1 and
a2 (Fig. 1). According to the notation commonly used
in spectroscopy, we denote conformations with
torsional angle of ϳ60Њ as gauche+ (g+), those about
−60Њ as gauche− (g−), and those of ϳ180Њ as trans (t).
We found that the most stable conformer in the gas
phase adopts g−gg geometry [15]. However, computa-
tions that take into account solvent effects showed that
in a polar continuum, characterized by the dielectric
constant of water (␧ = 80), the conformational prefer-
ence is altered (Table 2). Now, the g−gt conformer is
the most stable, followed by the g−gg conformer. This
stabilization of g−gt originates partly from its larger
dipole moment. Complexation with sodium ion
further stabilizes the g−gt conformation. Therefore,
for the purpose of interpretation of vibrational spectra
of MMP we considered g−gg and g−gt conformers to
be the candidates most likely occurring in solution and
crystalline samples. Indeed, the g−gt conformer has
been observed in the X-ray structure of guanosine–
O2Ј–PO2–CH2–O5Ј–cytidine dinucleotide [33].
However, we are aware that intermolecular inter-
actions present in the solid were disregarded. This is
because the crystal structures of alkylphosphonates
were not available in the literature and also because
of requirements for computational feasibility. More-
over, in aqueous solution, ion solvation by water
molecules compensates direct interionic interaction
[34]. As a result, both contact and water-separated
complexes may occur.
as the geometric mean of the corresponding diagonal
1
2
scale factors, Sij = (SiiSjj) . The program molvib [29]
and our program sqmvib [30] were used for this
purpose. The latter program was also employed for
calculation of IR and Raman intensities. The standard
expression based on the double-harmonic non-
resonant approximation was used for prediction of
IR intensities and Raman scattering activities. In the
right angle scattering geometry with exciting light
polarized perpendicularly to the scattering plane and
without and an analyzer, the Raman scattering activity
Sj of the jth normal mode was calculated as:
Sj = 45a2j + 7b2j
where a and b are the isotropic and anisotropic
invariants of the tensor of polarizability derivatives
We carried out full gradient optimization and vibra-
tional analysis at the HF/6-31G* level of g−gg and

ˇ
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
166
MMP differ for the g−gg and g−gt conformers. For g−
gg, 3-point coordination was found, with the K+ ion
interacting directly with the O1, O2 and O3 atoms.
For g−gt, the K+ ion lies in the PO1O2 plane (2-point
coordination) with a slight deviation (ЄPO1O2K Ϸ
20Њ) toward the C4 end of the molecule. The men-
tioned variations of the position of the potassium
ion with the MMP conformation can be considered
as an extreme case of the coupling between the
torsional and bond angles. This coupling is less pro-
nounced but not negligible for bond angles formed by
covalent bonds. For example, the PCO4 angle changes
from 116.9 to 113.5Њ when going from the g−gg to the
g−gt conformer of the MMP anion. It is worth noting
that this important structural effect is neglected by
many empirical molecular modeling methods.
Table 2
The energy differencea (kcal mol−1) between the g−gg and g−gt
conformers of the MMP anion and its sodium and potassium salts
HFb
PCMc
MMP anion
NaMMP
KMMP
2.1
−0.3
6.6
−1.7
−0.9
−0.7
aE(g−gt)−E(g−gg). This energy difference includes electronic
contributions, thermal contributions at 298 K, and electrostatic
solvation contributions (for the PCM mode).
bGas phase HF/6-31G* calculation.
cPCM HF/6-31G* calculation (␧ = 80).
g−gt conformations. Both the anions and the
complexes with Na+ and K+ ions were considered.
Calculated geometries are presented in Table 3. As
the impact of metal coordination on the magnitudes
of backbone torsional angles of the native anionic
form is modest, the conformational nomenclature
used for the MMP anion applies also to its sodium
and potassium salts.
We found no conformational dependence in the
coordination of the Na+ ion. This coordination is of
2-point type (see below) for both the g−gg and g−gt
conformers. In contrast, interactions of K+ ion with
3.2. Force constants
The unscaled HF/6-31G* harmonic force constants
expressed in internal coordinates are presented in
Table 4. By comparing the presented force constants
of MMP and NaMMP (KMMP) one can obtain
information about force-constant variations upon
interaction with the sodium and potassium ions and
Table 3
Calculateda geometries of MMP anion and MMP potassium and sodium salts in g−gg and g−gt conformations
Par.b
g−gg
Na g−gg
K g−gg
g−gt
Na g−gt
K g−gt
1.492
PO1
PO2
PO3
PC
1.476
1.504
1.498
1.599
1.827
1.401
1.399
1.413
112.4
122.8
104.2
114.0
115.3
−82.9
62.8
1.489
1.478
1.500
1.498
1.598
1.824
1.396
1.392
1.414
112.4
122.6
104.1
110.7
114.0
−88.0
59.0
1.483
1.645
1.846
1.414
1.393
1.395
1.485
1.631
1.811
1.399
1.400
1.412
1.476
1.644
1.844
1.409
1.380
1.396
1.490
1.594
1.813
1.394
1.390
1.412
CO4
O4C4
O3C3
O1PO2
C3O3P
O3PC
PCO4
CO4C4
C3O3PC
O3PCO4
PCO4C4
PMc
123.5
119.1
123.6
117.0
120.4
100.8
116.9
114.5
−90.2
66.6
78.2
–
117.7
107.2
115.9
115.2
−76.4
66.2
82.4
2.622
76.3
175.2
120.0
100.4
113.5
113.7
−95.4
60.8
179.0
–
121.0
105.8
112.2
113.9
−92.2
60.9
186.1
2.710
152.9
101.3
86.5
179.9
2.665
125.7
130.1
2.668
124.4
131.3
O3PM
CPM
–
–
–
–
aHF/6-31G*.
bBond lengths in angstroms, angles in degrees. For numbering see Fig. 1.
cM = Na+ or K+.

ˇ
167
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
Table 4
Conformational dependence of the diagonal HF/6-31G* force constantsa of methyl methoxymethanphosphonate
FCb
MMP
Na
K
g−gg
g−gt
g−gg
g−gt
g−gg
g−gt
nPO1
nPO2
nPO3
10.240
10.710
4.860
3.530
–
10.570
10.670
4.880
3.550
–
9.213
9.558
6.004
3.733
1.202
6.477
6.583
6.268
5.827
5.719
6.100
5.918
5.920
5.973
5.827
5.730
0.898
1.317
2.661
1.528
0.213
1.092
1.417
2.178
0.953
0.860
1.315
1.028
0.811
0.784
0.827
0.697
0.704
1.042
1.059
0.814
0.710
0.712
1.034
1.056
0.025
0.065
0.088
0.147
0.159
9.402
9.541
6.043
3.858
1.209
6.531
6.695
6.265
5.714
5.568
6.113
5.920
5.945
5.915
5.647
5.760
0.911
1.253
2.666
1.548
0.204
1.102
1.433
2.170
0.947
0.884
1.208
0.906
0.836
0.776
0.827
0.692
0.704
1.072
1.029
0.807
0.705
0.714
1.028
1.042
0.017
0.084
0.105
0.122
0.066
10.060
10.320
5.450
3.970
1.840
6.530
6.550
6.320
5.830
5.730
6.080
5.940
5.850
5.980
5.860
5.720
1.180
1.340
2.010
1.530
0.510
0.640
1.770
2.500
1.210
0.860
1.360
1.040
0.790
0.770
0.820
0.710
0.710
1.050
1.050
0.820
0.710
0.710
1.030
1.060
0.030
0.060
0.190
0.150
0.180
9.866
9.999
6.203
4.105
1.871
6.576
6.754
6.324
5.609
5.450
6.101
5.913
5.930
5.891
5.603
5.753
0.969
1.285
2.212
1.376
0.090
1.140
1.504
2.340
1.111
0.887
1.139
0.948
0.822
0.753
0.829
0.692
0.702
1.074
1.029
0.807
0.708
0.717
1.028
1.044
0.020
0.089
0.081
0.146
0.076
nPC
nPMc
nCO4
nO4C4
nO3C3
nCHs
6.060
6.760
6.790
5.760
5.640
5.950
5.700
5.740
5.880
5.830
5.530
1.090
1.380
1.830
1.500
–
6.080
6.980
6.780
5.660
5.500
5.960
5.660
5.790
5.790
5.490
5.590
1.080
1.290
1.820
1.510
–
nCHa
nC3Hs
nC3Ha1
nC3Ha2
nC4Hs
nC4Ha1
nC4Ha2
dC3OP
dC4OC
dPO12
dO3PC
dPM2
dPM1
dPOr
dPOw
dPOt
dCHs
dOCP
dCHr
dCHw
dCHt
dC3Hs
dC3a1
dC3a2
dC3r1
dC3r2
dC4Hs
dC4a1
dC4a2
dC4r1
dC4r2
tC3O3
tC4O4
tPO3
–
–
1.460
2.190
1.070
0.860
1.480
1.110
0.780
0.760
0.800
0.720
0.720
1.040
1.060
0.810
0.720
0.720
1.040
1.060
0.030
0.070
0.080
0.150
0.230
1.460
2.160
1.040
0.880
1.180
0.950
0.810
0.760
0.810
0.710
0.720
1.080
1.030
0.790
0.720
0.730
1.030
1.040
0.020
0.090
0.090
0.130
0.070
tPC
tCO4
a
−1
˚
˚
Unscaled values, in mdyn A and mdyn A for stretching and bending (torsional) FC types, respectively.
bFor definition of internal coordinates see Table 1.
cM = Na+ or K+.

ˇ
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
168
upon conformational transitions. Notably, the con-
formational transition g−gg → g−gt induces major
changes of the nO4C4 (stretching) and tCO4
(torsional) force-constants, while complex formation
reduces the nPO*, nO4C4, nO3C3 and increases the
nPC and nPO3 force-constants. The PO3 stretching
mode of the g−gg conformer is less affected by K+
coordination than that of the g−gt conformer, despite
the fact that in the g−gg form the K+ ion is coordinated
in the vicinity of the O3 atom. This finding suggests
the importance of including counter-ions explicitly
into calculations of solid-state spectra, as their
influence is difficult to predict empirically.
the rocking vibration of the methylene group. The
calculated frequencies (NaMMP, g−gt) of these
bands are 738, 830, and 898 cm−1, respectively. The
assignment of the nPO3 band is supported by the
agreement between calculated and observed intensi-
ties and depolarization ratios. In the Raman spectra of
NaMMP, the PO3 stretching band is split into two
components with nearly equal depolarization. This
phenomenon can be attributed to the presence of
two conformations in the sample. Indeed, we
predicted this band to be strongly conformationally
sensitive (Table 7). The calculated frequency
(723 cm−1) for the g−gg conformer of NaMMP corre-
sponds to the band observed at 727 cm−1, whereas the
738 cm−1 band calculated for the g−gt conformer
agrees with the observed 740 cm−1 band. However,
for KMMP, the spectral interpretation is less
straightforward.
3.3. Vibrational spectra
Tables 5 and 6 show the harmonic frequencies, IR
and Raman intensities, Raman depolarization ratios,
and spectral interpretation of NaMMP and DMMP,
respectively, calculated by the SQM HF/6-31G*
methodology. These results are compared with the
experimental data measured from aqueous solutions
and solid NaMMP and KMMP in Tables 5 and 6 and
Figs. 3–6.
The conformationally induced splitting can be
observed also for the PC stretching band. This split-
ting amounts to 26 cm−1 in the IR spectrum of
KMMP. Unfortunately, a lower Raman intensity of
this band and a relatively large error of the predicted
frequency and the depolarization ratio of this band
preclude any identification of involved conformers.
The mentioned inaccuracy of the calculated spectral
parameters of this band originates in part from the
uncertainty in the value of the PC stretching scale
factor. As mentioned in Section 2, the P–C stretching
force-constant was not adjusted in this study, but it
was scaled by the scale factor for the P–O stretching.
As a result, the calculated frequency of the PC
stretching mode is somewhat underestimated.
In the 20–600 cm−1 frequency region, vibrational
bands of bending and torsional vibrations of phos-
phonate and methyl groups are observed. Vibrational
bands predicted to lie in the region 20–150 cm−1
cannot be verified as there is no experimental
evidence. In the IR spectra of the sodium compound,
a broad band is observed near 210 cm−1. It can be
identified as a superposition of the four bands (191,
212, 234 and 253 cm−1), with main contributions from
bending vibrations and the nPNa stretching. A pair of
strong Raman bands 350 and 454 cm−1 in the NaMMP
spectra (315 and 438 cm−1 in the KMMP spectra)
originate from the PNa (PK) stretching vibration and
bending modes of the phosphonate group. The
medium 326 cm−1 band in the KMMP spectra
(Figs. 5 and 6), whose counterpart in the NaMMP
spectra was not observed, was interpreted as a bending
vibration of the C4–O4–C group. The clue to our
assignments was mainly the comparison of the
observed and predicted intensities, as in this region
supporting information of experimental depolariza-
tion ratios is missing.
The weak bands observed in the 860–900 cm−1
region are interpreted as originating from the rocking
vibration of the CH2 group. The conformational
splitting into two components also occurs for this
band.
The bands lying near 950 and 1050 cm−1 belong to
the in-phase combination of the stretching vibrations
of CO4 and O4C4 bonds (nsOC4), and to the stretch-
ing vibration of the O3C3 bond. These bands possess
alternating intensities: the former band is stronger in
Raman spectra, and the latter band in IR spectra. This
intensity pattern was successfully predicted by our
calculations.
The frequency region of 700–900 cm−1 is occupied
by stretching vibrations of PO3 and PC bonds, and by
The spectral profile in the 1090–1300 cm−1 region
is governed by the rocking vibrations of the methyl

ˇ
169
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
groups and the stretching vibrations of the PO1, PO2,
CO4, and O4C4 bonds. Both the in-phase (symmetric)
and out-of-phase (asymmetric) stretching vibrations
of the O1 and O2 anionic oxygens (hereafter denoted
as the nsPO* and naPO* bands, respectively) are
strong in the IR spectra, whereas in the Raman spectra
only the nsPO*mode is observed as a strong band.
While this intensity pattern is well reproduced by
our calculation, prediction of frequencies is somewhat
inaccurate. Although the same set of scale factors was
applied to both the NaMMP and KMMP spectra, the
predicted naPO* band of sodium compound coincides
with the band observed in aqueous solution, whereas
the naPO* band predicted for the potassium salt
coincides with the band observed in the spectra of
solid KMMP. The frequency gap between in-phase
and out-of-phase components is underestimated in
both the NaMMP and KMMP models (for instance,
a 128–143 cm−1 gap is observed whereas 102 cm−1
predicted for NaMMP). This discrepancy is due to
disregarded hydration and crystal structure effects.
As illustrated by the differences between experi-
mental vibrational spectra of solution and solid
NaMMP, these effects can significantly influence the
observed frequencies and intensities of the PO*
stretching bands.
stretching fundamentals and overtones of CH bending
vibrations can be expected in this region [37]. There-
fore, it is not surprising that our calculated results did
not accurately reproduce observed spectral features.
The agreement between the calculated and observed
spectra in this region could be improved by using
more than one scale-factor for the CH stretching
vibrations. This approach was however not attempted
since the transferability of such specific scale factors
would be doubtful.
4. Spectral manifestations of the inserted
methylene group
In Fig. 7, vibrational spectra of 1 M aqueous
solutions of dimethyl phosphate (DMP) and MMP
are compared. DMP serves here as a model of the
phosphate linkage of native nucleic acids. Topo-
logically, MMP can be considered as DMP with an
additional CH2 group inserted between phosphorus
and one ester oxygen.
Disregarding the stretching vibrations of methyl
groups, which are not present in nucleic acids,
Raman spectra of both compounds are dominated by
two strong bands at about 750 and 1150 cm−1. For
DMP, the 753 cm−1 band belongs to the in-phase
stretching vibration of the P–O–C bonds. The
Raman intensity and frequency of this band decrease
(to 738 cm−1) in MMP. This − 15 cm−1 frequency
shift was accurately reproduced by the SQM HF/6-
31G* calculations, which predict − 12 cm−1 shift
when going from the gg conformer of NaDMP (see,
for example Table 10 in Ref. [18]) to the g−gt
conformer of NaMMP. The symmetric stretching
vibration of the PO−2 group is observed in the solution
Raman spectra of DMP at 1083 cm−1. This band
shifts to lower wave-numbers (1062 cm−1) for MMP.
Also here the theoretically predicted frequency shift
of −25 cm−1 is in a good agreement with the
experimental data.
In the region of 1400–1500 cm−1, bending vibra-
tions of methyl groups are observed. The measured
frequencies are well predicted by our calculation, but
less successful reproduction of Raman intensities can
be noted. A similar phenomenon was encountered
also for the CH bending modes in ethane [35],
dimethyl phosphate [18] and cytosine [36]. We
concluded [25] that basis sets of triple-zeta quality
augmented with higher polarization and diffuse func-
tions should be used to reach agreement with Raman
intensities. Fortunately, except for vibrations of the
inserted methylene group, these bands will not be
observed in nucleic acids where the terminal methyl
groups will be replaced by deoxyribose.
Within the harmonic approximation, eight spectral
bands originating from the CH stretching normal
modes should lie in the 2800–3000 cm−1 frequency
region. However, a complicated spectral pattern
with about 12 spectral bands could be recognized in
the spectra of crystalline samples. This observation
indicates the large role played by intermolecular
interactions. Also, Fermi resonances between CH
The IR spectral bands assigned to the stretching
vibrations of the PO−2 group represent marker bands
for both DMP and MMP dissolved in aqueous
solution. These bands are observed at 1084 and
1208 cm−1, and 1062 and 1190 cm−1 in DMP and
MMP spectra, respectively. The calculated down-
shifts amount to −25 and −29 cm−1 for the symmetric

ˇ
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
170
Table 5
Experimental and calculateda vibrational spectra of Na MMP in solid state and aqueous solution
IR
Raman
Solid
Calculated (g−gt conformation)
Solid
Solution
Solution
HF/6-31G*b
exp.r
r
PEDc
49 (22.8, 5.1)
68 (0.5, 4.0)
0.75
0.74
0.75
0.73
0.73
0.65
0.75
0.74
0.26
0.39
0.20
0.15
0.69
dPNa2(62) − dPOw(16)
tC3O3(52) + tPO3(28)
tCO4(48) + dPNa2(19)
81 (7.2, 11.0)
105 (5.3, 0.7)
118 (9.1, 7.4)
142 (10.0, 3.3)
190 (10.3, 2.9)
235 (16.6, 6.4)
242 (16.3, 26.5)
263 (8.4, 5.0)
297 (9.5, 27.4)
328 (15.1, 21.5)
349 (24.5, 36.6)
tPC(52) − dPNa1(13) + tCO4(9)
dOCP(29) + dPOr(15) + dO3PC(12) + tPC(12)
tPO3(39) − tC3O3(16) + dPNa1(14)
dPNa1(29) − 5dOCP(24) − tPO3(17)
tC4O4(25) + dPOt(17) − dO3PC(16) − dC3OP(14)
nPNa(39) + dC3OP(25)
tC4O4(54) − nPNa(14) − tPC(10)
tO3PC(28) − dPOt(10) + nPNa(10)
dC4OC(48) + dPOt(21)
161 wd
191 w
212 w
234 w
253 w
204 w
221 w
250 w
308 w
344 w
350 s
454 s
nPNa(18) + dO3PC(16) − dPOw(14) + dPOt(13) −
nPC(11)
446 w
457 w
489 w
544 m
555 sh
730 w
735sh
440 w
433 (66.3, 20.8)
0.43
0.62
dPO12(50) + dPOr(18) + dPOw(15)
488 s
557 w
479 w
540 w
511 (22.7, 31.3)
558 (132.5, 23.4)
0.40
0.48
0.37
0.35
dPOr(26) − dC3OP(21) − dPO12(17) − dPOw(15)
dPOw(40) − dPO12(21) + dO3PC(10)
727 s
740 s
715 sh
734 s
0.03
0.03
0.00
0.01
0.11
0.15
0.24
0.14
0.08
0.58
0.58
nPO3(43) + nPC(14) + nO3C3(14)
nPC(34) − dPOw(14) − nPO3(13)
dCHr(60) + dCHt(12)
738 (36.3, 142.7)
830 (117.0, 43.1)
798 sh
811 m
868 w
890 w
962 s
778 sh
814 sh
868 w
880 w
947 m
1043 sh
800 m
868 w
888 w
898 (42.3, 15.2)
943 (45.8, 78.2)
1050 (285.2, 19.4)
953 w
0.34
0.73
nCO4(43) + nO4C4(35)
nO3C3(67) − nPO3(17)
1046 m
1074 sh
1084 s
1109 m
1112 sh
1040 sh
1043 w
1062 s
1107 w
1097 s
1108 s
1115 s
1161 w
1062 s
1106 m
1090 (486.4, 84.3)
1108 (38.9, 59.5)
0.04
0.64
0.08
0.74
nPO1(41) + nPO2(28)
nO4C4(49) − nCO4(25)
1158 w
1152 (5.7, 51.2)
1153 (1.8, 33.5)
1181 (45.4, 28.6)
1201 (10.4, 12.8)
1221 (86.8, 39.5)
1192 (346.8, 24.7)
0.55
0.75
0.75
0.74
0.43
0.74
0.72
dC4r1(68) + dC4r2(24)
dC3r2(91)
dC3r1(81)
dC4r2(47) − nCO4(14) − dC4r1(12)
dCHt(75)
nPO2(37) − nPO1(33)
1178 sh
1199 w
1221 m
1240 s
1176 w
1193 w
1225 m
1239 w
1250 w
1229 w
1190 s
1230 w
1188 w
0.60
0.63
1246 sh
1361 (1.9, 9.8)
0.14
0.74
0.66
0.68
0.75
0.74
0.74
0.73
0.37
0.06
0.66
0.75
0.03
dCHw(76)
dCHs(63) − dC4Hs(34)
dC3Hs(92)
dC4Hs(41) + dCHs(21) + dC4a2(21)
dC4a1(71) − dC4a2(22)
dC3a1(75)
dC4a2(43) − dC4Hs(18) + dC4a1(14)
dC3a2(80)
nC4Hs(46) − nCHs(46)
nCHs(49) + nC4Hs(42)
nCHa(94)
nC4Ha1(73) + nC4Ha2(25)
nC3Hs(99)
1424 w
1447 w
1452 w
1460 w
1420 w
1432 w
1451 w
1430 m
1440 m
1451 m
1463 m
1423 sh
1432 m
1452 m
1439 (23.5, 77.4)
1450 (2.4, 27.2)
1459 (0.1, 19,7)
1461 (3.5, 103.2)
1466 (0.3, 70.2)
1477 (4.8, 119.9)
1480 (4.1, 63.0)
2800 (36.7, 13.3)
2811 (72.6, 352.0)
2842 (33.0, 91.3)
2847 (96.1, 140.9)
2863 (57.8, 216.3)
0.65
0.90
0.67
1468 w
1474 s
1468 m
0.73
2817 w
2827 w
2835 w
2861 w
2877 w
2820 s
2829 s
2836 s
2867 s
2893 s
2834 s
2853 s
2876 s
2906 s
0.01
0.01
0.39
0.08
2835 w
2853 w

ˇ
171
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
Table 5 Continued
IR
Raman
Solid
Calculated (g−gt conformation)
Solid
Solution
Solution
HF/6-31G*b
exp.r
r
PEDc
2917 w
2935 w
2923 s
2939 s
2953 sh
2970 w
3001 s
3010 s
2945 sh
2957 s
2916 (50.3, 172.2)
2933 (42.0, 149.5)
0.12
0.03
0.52
0.72
nC4Ha2(67) − nC4Ha1(22) + nC4Hs(11)
nC3Ha1(99)
2943 w
2956 w
2966 w
3005 m
2939 (30.8, 75.8)
0.65
0.75
nC3Ha2(99)
3009 w
aSQM HF/6-31G* force field.
bFrequency (cm−1). Within parentheses are given IR intensity (km mol−1) and Raman differential cross-section (10−36 m2 sr−1).
cPotential energy distribution (PED). Contributions less than 10% were truncated.
dExperimental intensities are abbreviated as s (strong), m (medium), w (weak), sh (shoulder).
and asymmetric vibrations, respectively. In the DMP
spectra additional strong CO stretching bands appear
near 1050 cm−1. The relative IR intensity of these
bands decreases in the MMP spectra so that they
can be seen only as a shoulder on the nsPO band.
Also this spectral feature was well reproduced by
our calculations of NaDMP and NaMMP in the gg
and g−gt conformations, respectively.
In addition, two medium bands at 947 and
1106 cm−1 with contributions from the vibrations of
the methylene group can be distinguished in the
Raman and IR spectra of aqueous solution of MMP,
respectively, Since the PC stretching band is observ-
able only in the spectra of the solid samples (near
800 cm−1), there is no strong spectral band that
would be characteristic of MMP and in general of
phosphonate esters. The similar conclusion was also
reached by Thomas and Chittenden [12]. The indirect
spectral indications as frequency shifts are of limited
diagnostic value, since they can be easily inter-
changed with conformation dependent spectral
changes.
spectrum of aqueous solution of NaMMP is pre-
sented.) It leads to the conclusion that variations
observed in solid spectra are due to different counter-
ions, which are coordinated directly to MMP, and that
in solution coordination of counter-ions is indirect,
mediated by one or more water shells. Thus, models
disregarding interaction with water molecules are a
more appropriate description of counter-ion coordi-
nation in the solid state than in solution. Conse-
quently, the observed differences in the spectra of
crystals and aqueous solutions cannot be theoretically
predicted at our level of theory. Also, we could not use
additional structural information since the X-ray
structure of MMP is not available.
As mentioned above, K+ ion binds differently to
different conformations of MMP. Therefore, in the
calculated spectra of KMMP, conformation-
dependent spectral variations (Table 7) are super-
imposed on the shifts due to different positions of
the K+ ion. For example, a comparison of the calcu-
lated spectral shifts induced by the g−gg → g−gt tran-
sition reveals that the 20 cm−1 shift of nC3O3 mode
(ϳ1050 cm−1) in KMMP does not result from the
transition itself, but it must be attributed to the alteration
of the position of the potassium ion. The largest varia-
tions between the NaMMP and KMMP spectra occur
for the PO* stretching modes. A more detailed study of
the dependence of the PO2− frequencies with the nature
of the cation was presented by Thomas and Chitten-
den [14]. For the 2-ethylhexyl phosphonate ester they
noted that the frequencies of the nsPO and naPO modes
decrease with increasing cation mass. This trend was
not correctly reproduced by our calculations, probably
due to the neglected crystal structure effects.
5. Variations of vibrational spectra with the nature
of the complexed counter-ion and with
conformation
Observed vibrational spectra of the sodium and
potassium salts in the solid state differ somewhat.
For concise summary of the positions of intense (diag-
nostic) bands see Table 7. These changes are correctly
reproduced by our calculations. Interestingly, solution
spectra of both salts are identical. (Thus, only the

ˇ
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
172
Table 6
Experimental and calculateda vibrational spectra of KMMP in the solid state
IR
Raman
Solid
Calculated (g−gt conformation)
Solid
HF/6-31G*b
r
PEDc
23 (17.3, 5.3)
73 (1.9, 5.5)
0.75
0.75
0.74
0.73
0.73
0.63
0.74
0.55
0.30
0.75
0.10
0.21
0.75
0.69
0.38
0.49
dPK2(62) − PK(15) − dPOw(10)
tC3O3(43) + tPO3(40)
tCO4(60) − dO3PC(15)
82 (3.0, 11.5)
109 (5.6, 4.5)
114 (6.4, 4.5)
144 (13.5, 2.1)
166 (2.8, 4.1)
235 (12.1, 3.2)
254 (2.9, 5.6)
283 (4.9, 4.7)
312 (20.0, 14.2)
325 (30.7, 40.6)
356 (4.8, 40.3)
423 (80.6, 30.4)
514 (25.0, 38.4)
560 (131.0, 19.4)
tPC(40) − dPK1(28) − dOCP(10)
tC3O3(21) + tCO4(18) + dOCP(11) + tPC(11)
dPK1(31) + tPC(25) − tC3O3(16)
dOCP(36) + tPO3(23)
nPK(34) − dO3PC(23) − tC4O4(11)
tC4O4(41) − dC3OP(24) + dPK1(11)
tC4O4(27) + dC3OP(17) − tPC(12) − nPK(10)
nPK(25) + dO3PC(23) + dC4OC(11)
dC4OC(40) + nPC(15) − nPK(11) − dPO12(10)
dPOt(47) + dC4OC(12)
265 md
315 s
326 s
348 m
438 s
489 m
543 m
437 m
489 m
544 s
dPO12(48) + dPOr(15) + dPOw(14)
dPOr(30) − dC3OP(20) − dPO12(18)
dPOw(56) − dC4OC(9) − dOCP(9) + dO3PC(9)
728 w
760 m
778 m
804 m
873 w
880 sh
939 m
1053 s
1075 s
1112 s
761 s
777 m
750 (31.9, 129.4)
844 (117.8, 28.7)
0.11
0.64
nPO3(40) + nO3C3(14) + nPC(14)
nPC(33) − dPOw(12) − nPO3(10) + dCHr(10)
881 w
941 s
1049 m
1078 s
1119 s
1159 w
895 (52.1, 19.1)
952 (55.5, 79.1)
1053 (286.4, 18.0)
1101 (436.7, 53.0)
1112 (33.2, 57.2)
1153 (2.7, 53.7)
1154 (2.2, 37.0)
1184 (48.9, 27.3)
1201 (60.8, 12.9)
1209 (22.6, 43.8)
1246 (347.5, 8.9)
1363 (2.8, 73)
1439 (24.0, 73.1)
1453 (3.1, 27.8)
1459 (0.5, 23.9)
1463 (3.0, 101.4)
1469 (0.9, 76.8)
1477 (3.8, 90.6)
1478 (4.8, 91.3)
2755 (94.1, 131.9)
2798 (83.1, 235.4)
2834 (23,0, 92.1)
2839 (105.1, 156.9)
2861 (57.8, 218.2)
0.41
0.35
0.75
0.07
0.75
0.75
0.74
0.72
0.57
0.74
0.62
0.43
0.75
0.64
0.68
0.75
0.74
0.73
0.75
0.26
0.06
0.27
0.65
0.03
dCHr(53) + dCHt(11) + dPOw(10)
nCO4(39) + nO4C4(38)
nO3C3(66) − nPO3(16)
nPO1(37) + nPO2(25) + nO4C4(10)
nO4C4(43) − nCO4(23) − nPO2(11)
dC4r1(64) + dC4r2(26)
dC3r2(93)
dC3r1(83)
dC4r2(44) − dC4r1(20) − nCO4(20)
dCHt(75)
nPO2(45) − nPO1(43)
dCHw(77)
dCHs(72) − dC4Hs(25)
dC3Hs(90)
dC4Hs(46) + dC4a1(22) + dCHs(14)
dC41(52) − dC4a2(36)
dC3a1(79)
dC3a2(41) + dC4a2(21) − dC4Hs(10)
dC3a2(45) − dC4a2(23) + dC4Hs(11)
nCHs(66) − nCHa(32)
nC4Hs(83)
1157 w
1187 m
1201 sh
1214 sh
1236 s
1201 m
1218 sh
1240 m
1425 w
1445 m
1426 m
1446 sh
1457 m
1466 m
1458 m
1471 m
2819 sh
2828 w
2843 w
2864 sh
2880 w
2900 w
2920 w
2940
2820 s
2830 s
2844 s
2866 s
2881 s
2900 s
2921 sh
2942 s
2960 s
2971 sh
3001 s
nCHa(63) + nCHs(31)
nC4Ha1(66) + nC4Ha2(26)
nC3Hs(99)
2913 (52.8, 176.0)
2929 (45.2, 135.2)
2937 (34.7, 95.3)
0.51
0.70
0.75
nC4Ha2(69) − nC4Ha1(19) + nC4Hs(11)
nC3Ha1(80) + nC3Ha2(20)
nC3a2(80) − nC3Ha1(20)
2970 w
2999 w
aSQM HF/6-31G* force field.
bFrequency (cm−1). Within parentheses are given IR intensity (km mol−1) and Raman differential cross-section (10−36 m2 sr−1).
cPotential energy distribution (PED). Contributions less than 10% were truncated.
dExperimental intensities are abbreviated as s (strong), m (medium), w (weak), sh (shoulder).

ˇ
173
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
Fig. 3. Infrared spectra of sodium MMP. Top: spectrum calculated by using SQM HF/6-31G* force field of the g−gt conformer. Middle: FTIR
spectrum in KBr (4000–400 cm−1)and CsI (400–100 cm−1) pellets. Bottom: FTIR spectrum of 1 M solution in H2O.
As a whole, the anionic form of MMP and its
sodium and potassium salts exhibit fairly character-
istically and qualitatively the same nature of spectral
variations upon conformational transitions. The com-
parison presented in Table 7 indicates that the g−gt
conformer is the dominant form in the measured
samples. Obviously, both the frequency and intensity
patterns predicted for this form are much closer to the
measured data than the results for g−gg or models that
disregard counter-ions. However, this should be
regarded with caution, since only conformers with
the lowest calculated energies were included in the
spectral calculations. Also, it should be noted that a
more conclusive experimental study would require
measurement of the vibrational spectra of MMP
from non-polar solvents where the conformation
stability is predicted to change (Table 2). This
approach was recently used in the investigation of
conformation equilibria in trimethyl phosphate [38].
Unfortunately, due to its ionic character, MMP is
insoluble in non-polar solvents.
6. Conclusions
Methyl methoxymethanphosphonate is the simplest
structural analogue of the phosphodiester bond
modified by insertion of the methylene group. We

ˇ
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
174
Fig. 4. Raman spectra of sodium MMP. Top: spectrum calculated by using SQM HF/6-31G* force field of the g−gt conformer. Middle: Raman
spectrum of polycrystalline solid. Bottom: polarized Raman spectra (I// and IЌ) of 1 M solution in H2O.
have measured Raman and IR spectra of the title
compound in aqueous solution and in the solid
phase. These spectra are reported for the first time.
The spectral interpretation was done by using a fully
generic force field obtained from ab initio calcula-
tions. Such an approach was capable of predicting
correctly subtle spectral changes induced by the
mentioned chemical modification. This finding con-
firms the transferability of the scale factors developed
for the dimethyl phosphate on a larger set of organo-
phosphorus compounds. In addition, we identified low
energy rotational isomers of MMP that prevail in
the solid state and aqueous solution, and the
conformationally sensitive spectral bands.
Acknowledgements
This work was supported by the Grant Agency of
the Czech Republic (grant no. 203/93/2362). The cal-
culations were carried out at the Supercomputing
Center of Charles University, Prague. The kind help
of Dr Ivan Rosenberg, Dr Zdeneˇk Tocˇik and Prof Ivan
Barv´ık is gratefully acknowledged.
Note added in proof
Recent hybridization studies have shown that
MMP-containing oligonucleotides have lower

ˇ
175
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
Fig. 5. Infrared spectra of potassium MMP. Top: spectrum calculated by using SQM HF/6-31G* force field of the g−gt conformer. Bottom:
FTIR spectrum in KBr (4000–400 cm−1) pellet.
Fig. 6. Raman spectra of potassium MMP. Top: spectrum calculated by using SQM HF/6-31G* force field of the g−gt conformer. Bottom:
Raman spectrum of polycrystalline solid.

ˇ
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
176
Table 7
Prediction of the conformation-dependent changes of the diagnostic IR and Raman bands of MMP
Experimentala
Na
Calculatedb
MMP anion
K
NaMMP
KMMP
Assignment
Solid Solution Solid g−gg
g−gt
g−gg
g−gt
738(36,143)
830(117,43)
898 (42, 15)
g−gg
g−gt
750(32,129)
844 (118, 29) naPO
895 (52, 19) dCHr
1053 (286, 18) nO3C3
735
806
889
734
814
880
761
804
881
739(45,153)
788 (103, 52)
865(123,37)
751(74,127) 723(23,168)
823(128,44) 807 (74, 51)
879 (28, 22) 880 (128, 46)
1054(220,24) 1050(229,21)
926 (66, 66) 908 (10, 69)
722(51,127)
817 (71. 60)
872 (168, 18)
nsPO
1045 1043
957 947
1051 1058(357,38)
940 894 (17, 75)
1050 (285, 19) 1035(261,34)
943(46,78) 907 (27, 80)
952(56,79)
nOC4
nsOC4
nsPO*
naPO*
1109 1107
1090 1062
1240 1190
1116 1079 (113, 41) 1087(62,56) 1098 (113, 48) 1108(39,60)
1077 1045(128,33)
1238 1246(377, 10) 1258(325,14) 1198(346,15)
1083 (195, 41) 1112 (33, 57)
1112 (117, 45) 1101(437,53)
1263 (239, 18) 1246(348,9)
1063(399,50) 1081(367,59)
1090(487,84)
1192(347,25)
aMean value of band frequency (cm−1) from IR and Raman spectrum.
bSQM HF/6-31G* force field. Within parentheses are given IR intensities (km mol−1) and Raman differential crossection (10−36 m2 sr−1).
Fig. 7. Comparison of vibrational spectra of 1 M aqueous solution of sodium DMP and sodium MMP. Top: polarized Raman spectra (I// and IЌ)
of NaDMP. Middle-top: polarized Raman spectra (I// and IЌ) NaMMP. Middle-bottom: FTIR spectrum of NaDMP. Bottom: FTIR spectrum of
NaMMP.

ˇ
177
M. Strajbl et al./Journal of Molecular Structure 415 (1997) 161–177
[21] J.H. Wachters, J Chem. Phys. 52 (1970) 1033.
[22] S. Miertus, J. Tomasi, Chem. Phys. 65 (1982) 239.
[23] S. Miertus, E. Scrocco, J. Tomasi, Chem. Phys. 55 (1981) 117.
[24] A. Bondi, J. Chem. Phys. 64 (1964) 441.
binding affinities for the complementary single-
stranded DNA and RNA targets, and that their
affinities for DNA duplexes and noncomplementary
single-stranded DNAs are similar to wild-type
oligonucleotides [39,40].
[25] M.J. Frisch, G.W. Trucks, M. Head-Gordon, P.M.W. Gill,
M.W. Wong, J.B. Foresman, B.G. Johnson, H.B. Schlegel,
M.A. Robb, E.S. Replogle, R. Gomperts, J.L. Andres, K.
Raghavachari, J.S. Binkley, C. Gonzalez, R.L. Martin, D.J.
Fox, D.J. Defrees, J. Baker, J.J.P. Stewart, J.A. Pople, gaussian
92, Revision G.4, Gaussian, Inc., Pittsburgh, PA, 1992.
[26] M.J. Frisch, G.W. Trucks, H.B. Schlegel, P.M.W. Gill,
B.G. Johnson, M.A. Robb, J.R. Cheeseman, T. Keith,
G.A. Petersson, J.A. Montgomery, K. Raghavachari,
M.A. Al-Laham, V.G. Zakrzewski, J.V. Ortiz, J.B. Foresman,
J. Cioslowski, B.B. Stefanov, A. Nanayakkara, M.
Challacombe, C.Y. Peng, P.Y. Ayala, W. Chen, M.W.
Wong, J.L. Andres, E.S. Replogle, R. Gomperts, R.L. Martin,
D.J. Fox, J.S. Binkley, D.J. Defrees, J. Baker, J.P. Stewart,
M. Head-Gordon, C. Gonzalez, J.A. Pople, gaussian 94,
Revision C.2, Gaussian, Inc., Pittsburgh, PA, 1995.
[27] J. Floria´n, J. Phys. Chem. 97 (1993) 10649.
References
[1] I. Rosenberg, A. Holy´, Coll. Czech. Chem. Commun. 52
(1987) 2572.
[2] I. Rosenberg, A. Holy´, Coll. Czech. Chem. Commun. 50
(1985) 1507.
[3] E. Uhlman, A. Peyman, Chem. Rev. 90 (1990) 544.
[4] J.S. Cohen, Antiviral Res. 28 (1995) 366.
[5] T.S. Crooke, Annu. Rev. Pharmacol. Toxicol. 32 (1992) 329.
[6] A.D. Mesmaeker, K.-H. Altmann, A. Waldner, S. Wendeborn,
Current Opinion Struct. Biol. 5 (1995) 343.
[7] A.D. Mesmaeker, R. Ho¨ner, P. Martin, H.E. Moser, Acc.
Chem. Res. 28 (1995) 366.
[28] W.B. Person, in: W.B. Person, G. Zerbi (Eds.), Vibrational
Intensities of Infrared and Raman Spectroscopy, Elsevier,
Amsterdam, 1982.
[8] J.M. Veal, F.K. Brown, J. Am. Chem. Soc. 117 (1995) 1873.
[9] U. Heinemann, L.-F. Rudolph, C. Alings, M. Morr, W.
Heikens, R. Frank, H. Blo¨cker, Nucleic Acid Res. 19 (1992)
427.
[29] T. Sundius, J. Mol. Struct. 218 (1990) 321.
[30] J. Floria´n, SQMVIB: A computer program for calculation of
scaled quantum mechanical vibrational spectra of molecules,
Charles University, Prague, 1994.
[31] R.D. Amos, Chem. Phys. Lett. 124 (1986) 376.
[32] P.L. Polavarapu, J. Phys. Chem. 94 (1990) 8106.
[33] I. C´ısarˇova´, J. Zachova´, I. Rosenberg, Z. Tocˇik, Nucleosides
and Nucleotides, submitted for publication.
[34] A. Warshel, S.T. Russell, Quart. Rev. Biophys. 17 (1984) 283-
422.
[35] B.G. Johnson, J. Florian, Chem. Phys. Lett. 247 (1995) 120-225.
[36] J. Floria´n, V. Baumruk, J. Leszczynski, J. Phys. Chem. 100
(1996) 5578-5589.
[10] A. Tramontano, K.D. Janda, R.A. Lerner, Science 234 (1986)
1566-1570.
[11] P.A. Bartlett, C.K. Marlowe, Biochemistry 22 (1983) 4618-
4628.
[12] L.C. Thomas, R.A. Chittenden, Spectrochim. Acta 21 (1965)
1905.
[13] R.A. Nyquist, The Interpretation of Vapor Phase Infrared
Spectra, 1984, Sadtler Research Laboratories, Philadelphia.
[14] R.C. Thomas, R.A. Chittenden, Spectrochim. Acta 26A (1970)
781.
ˇ
[15] M. Strajbl, J.Floria´n, J. Biomol. Str. Dyn. 13 (1996) 687.
[16] Y. Guan, C.J. Wurrey, G.J. Thomas, Jr., Biophys. J. 66 (1994)
[37] N.B. Colthup, L.H. Daly, S.E. Wiberley, Introduction to
Infrared and Raman Spectroscopy, 3rd edn., Academic
Press, Inc., San Diego, 1990.
[38] R. Streck, A.J. Barnes, W.A. Herrebout, B.J. Vanderveken,
J. Mol. Struct. 376 (1996) 277.
225.
[17] Y. Guan, S.-C. Choy, R. Glaser, J. Thomas, Jr., J. Phys. Chem.
99 (1995) 12054.
[18] J.Floria´n, V. Baumruk, M. Strajbl, L. Bedna´rˇova´, J. Steˇpa´nek,
J. Phys. Chem. 100 (1996) 1559.
ˇ
ˇ
[39] B. Haly, L. Bellon, V. Mohan, Y, Sanghvi, Nucleosides &
Nucleotides 15 (1996) 1383.
[40] T. Kofoed, P.B. Rasmussen, P. Valentin-Hansen and E.B.
Pedersen, Acta Chemica Scandinavica 51 (1997) 318.
[19] G. Fogarasi, P. Pulay, in: J.R. Durig (Ed.) Vibrational Spectra
and Structure, Vol. 14, Elsevier, Amsterdam, 1985, p. 125.
[20] J. Epstein, R.W. Rosenthal, R.J. Ess, Anal. Chem. 27 (1955)
1435.