IR-Raman, NMR and density functional methods in the examination of tautomerism and features of N-methyl substituted 9-acridinamine derivatives

Article abstract of DOI:10.1016/S0022-2860(98)00530-4

Four N-methyl substituted derivatives of amino or imino forms of 9- acridinamine were synthesized and subjected to detailed IR-Raman and NMR (¹H and ¹³C) investigations. Harmonic frequencies predicted at the density functional (DFT) level enabled certain modes to be assigned to bands in IR or Raman spectra and those characteristic of either the amino or imino tautomeric forms of 9-acridinamine. Theoretical ¹H and ¹³C chemical shifts, particularly the latter, fit the relevant NMR spectra only qualitatively; both demonstrate a unique pattern for each of the compounds studied. The derivatives examined seem to exhibit their own identity and features, reflected in unique vibrational and NMR spectra, rather than retain those of the parent tautomeric forms of 9-acridinamine. Both experimental and theoretical investigations reveal that two tautomeric forms of N-methyl-9- acridinamine, in similar to 9-acridinamine, should co-exist at room temperature. The polarity of the compounds, expressed by dipole moments, as well as distribution of relative atomic partial charges and electrostatic potential around the molecules, are unique for each of the compounds but generally similar in the groups of derivatives originating from the amino or imino tautomers of 9-acridinamine.

Full text of DOI:10.1016/S0022-2860(98)00530-4

Journal of Molecular Structure 476 (1999) 45–55
IR–Raman, NMR and density functional methods in the examination
of tautomerism and features of N-methyl substituted
9-acridinamine derivatives
Janusz Rak, Karol Krzymin´ski, Piotr Skurski, Ludwika Jo´z´wiak, Jerzy Blazejowski,*
˙
Department of Chemistry, University of Gdan´sk, J. Sobieskiego 18, 80-952 Gdan´sk, Poland
Received 1 April 1998; accepted 9 June 1998
Abstract
Four N-methyl substituted derivatives of amino or imino forms of 9-acridinamine were synthesized and subjected to detailed
IR–Raman and NMR (1H and 13C) investigations. Harmonic frequencies predicted at the density functional (DFT) level
enabled certain modes to be assigned to bands in IR or Raman spectra and those characteristic of either the amino or imino
1
tautomeric forms of 9-acridinamine. Theoretical H and 13C chemical shifts, particularly the latter, fit the relevant NMR spectra
only qualitatively; both demonstrate a unique pattern for each of the compounds studied. The derivatives examined seem to
exhibit their own identity and features, reflected in unique vibrational and NMR spectra, rather than retain those of the parent
tautomeric forms of 9-acridinamine. Both experimental and theoretical investigations reveal that two tautomeric forms of N-
methyl-9-acridinamine, in similar to 9-acridinamine, should co-exist at room temperature. The polarity of the compounds,
expressed by dipole moments, as well as distribution of relative atomic partial charges and electrostatic potential around the
molecules, are unique for each of the compounds but generally similar in the groups of derivatives originating from the amino
or imino tautomers of 9-acridinamine. ᭧ 1999 Elsevier Science B.V. All rights reserved.
Keywords: N-Methyl-9-acridinamines; Tautomerism; IR–Raman spectroscopy; NMR spectroscopy; Experimental and theore-
tical investigations
1. Introduction
In the past, some authors followed up this idea [6–
10], while others did not recognize it [11–16]. To
shed more light on the tautomerism of 9-acridinamine
we have attempted, among other things, to synthesize
some simple derivatives with ‘blocked’ the amino or
imino structure. In this publication we present synth-
eses as well as the results of IR–Raman and NMR
investigations of four such compounds: N-methyl-9-
acridinamine (1), 10-methyl-9-acridinimine (3), N,N-
dimethyl-9-acridinamine (4), and N-methyl-10-
methyl-9-acridinimine (5) (Fig. 1). Parallel, structural
optimizations and determinations of harmonic
Our recent semiempirical [1–3] and ab initio [4]
quantum mechanical calculations, as well as examina-
tions of electronic absorption [2], fluorescence [5],
vibrational [4] and NMR [4] spectra, have revealed
that 9-acridinamine can potentially exist in two tauto-
meric forms—amino or imino—in equilibrium with
each other.
* Corresponding author. Tel.: +48-58-345-0331; Fax: +48-58-
341-0357; E-mail: bla@ewa.chem.univ.gda.pl
0022-2860/99/$ - see front matter ᭧ 1999 Elsevier Science B.V. All rights reserved.
PII: S0022-2860(98)00530-4

46
J. Rak et al. / Journal of Molecular Structure 476 (1999) 45–55
frequencies, chemical shifts and some physicochem-
ical features of five molecules originating from amino
or imino forms, i.e. the four above-mentioned and N-
methyl-(10-H)-acridinimine (2), were carried out at
the DFT level. The aim of these studies was to reveal
the spectral peculiarities of two types (amino and
imino) of 9-acridinamine methyl derivatives, as well
as factors determining their ability to intermolecular
interactions.
9-Acridinamine is one of the simplest representa-
tives of the family of heterocyclic nitrogenous bases
and a molecule with a well-recognized biological
relevance [17,18]. It exhibits distinctive mutagenic
activity [19–21] and the ability to interact with
DNA [22–28] and other biologically important mole-
cules [24,29,30]. It also appears to be a convenient
probe for investigating various physical features of
biological systems [31,32] and it is, therefore, impor-
tant to know whether simple derivatives of 9-acridi-
namine with fixed structures of both tautomeric forms
can be synthesized and investigated experimentally,
and what impact the structure may have on their
features, including biological activity. This work
has extended our knowledge in the first of these
topics.
2. Experimental
2.1. Syntheses
N-methyl-9-acridinamine (1) and N,N-dimethyl-9-
acridinamine (4) hydrochlorides were synthesized by
heating 9-phenoxyacridine (obtained from 9-chloro-
acridine [17,33,34]) with methanamine and N-methyl-
methanamine hydrochloride, respectively, dissolved
in phenol [17]. N-methyl-9-acridinamine free base
was released from the aqueous solution of its hydro-
chloride by alkalization with sodium hydroxide,
extraction with toluene and purification by column
chromatography (phase: silica gel 60 from Merck;
eluent: toluene/N-methylmethanamine = 10/1) (m.p.
= 446–447 K, lit. = 446–447 K [17]). N,N-dimethyl-
9-acridinamine free base was also released from the
Fig. 1. DFT (B 3LYP)/6-31G** optimized geometries of N-
methyl-9-acridinamine (1), N-methyl-9(10-H)-acridinimine (2),
10-methyl-9-acridinimine (3), N,N-dimethyl-9-acridinamine (4)
and N-methyl-10-methyl-9-acridinimine (5).

47
J. Rak et al. / Journal of Molecular Structure 476 (1999) 45–55
aqueous solution of its hydrochloride by alkalization
with N-methylmethanamine, extraction with light pet-
roleum, separation and repeated crystallization [17]
from cyclohexane in an inert atmosphere (m.p. =
332–333 K, lit. = 334 [17]). The purity of the products
was checked by TLC, their chemical composition
proved by elemental analysis using a Carlo–Erba
(model EAGER 200) instrument (% found/theoreti-
cal: C = 80.71/80.78, H = 5.85/5.78 and N = 13.51/
13.44 for 1; C = 81.12/81.08, H = 6.41/6.31 and
N = 12.63/12.61 for 4), and identity of 4 confirmed by
X-ray investigations [35].
10-Methyl-9-acridinimine (3) hydriodide was synthe-
sized by heating 9-acridinamine with iodomethane, both
dissolved in methanol, in a sealed tube at 373 K [36,37].
The salt was subsequently separated, dissolved in water
and treated with cool dilute NaOH. The 10-methyl-9-
acridiniminium hydroxide so obtained was purified
chromatographically (phase: silica gel 60; eluent:
toluene/N-ethylethanamine = 10/1) and heated in a
vacuum pistol over P2O5 at 403 K. The final product
was recrystallized from dry cyclohexane in an inert
atmosphere, always in the form of thin orange–yellow
needles (m.p. = 407–408 K, lit. = 407–409 K [36]). Its
purity was checked by TLC and its composition con-
firmed by elemental analysis (% found/theoretical: C =
80.80/80.78, H = 5.72/5.78, N = 13.56/13.44).
1 (or 2), 3, 4 and 5 in CD3CN were recorded on a
Varian Unity 500 Plus spectrometer. 1D spectra were
collected under standard conditions and chemical
1
shifts were referred to the relevant H or 13C nuclei
signals in tetramethylsilane (TMS; reference). HSQC
and HMBC spectra were acquired by employing the
pulsed field gradient technique [38].
Infrared spectra 1 (or 2), 3, 4 and 5 dispersed in KBr
(4000–400 cm−1 region) or polyethylene (400–
100 cm−1 region) were recorded on a Bruker IFS 66
FTIR instrument at a resolution varying between 1
and 4 cm−1. Raman scattering measurements (resolu-
tion 2 cm−1) were carried out on samples of the pure
compound (powdered) using a Bruker FRA 106 FT-
module connected with an FTIR system (an Nd3+/
YAG laser (1064 nm) served as the excitation source).
2.3. Calculations
Unconstrained geometry optimizations of isolated
molecules were conducted at the density functional
(DFT) [39] level of theory using gradient techniques
[40,41], 6-31G** [42,43] basis sets and the Becke
3LYP (B3LYP) nonlocal spin density functional
approximation, which uses Becke’s nonlocal
exchange functional [44,45] and the Lee–Yang–Parr
nonlocal correlation functional [46]. DFT geometry
optimizations were extended in the case of 3 and 4
utilizing the self-consistent reaction field (SCRF)
model [47,48] which simulates the presence of the
solvent. In the latter calculations the relative electric
constant of acetonitrile (CH3CN) was assumed to be
38.8, and the spherical cavity radii were evaluated at
N-Methyl-10-methyl-9-acridinimine
(5)
was
synthesized by treating N-methyl-9-acridinamine
(for 12 h at room temperature) with a stoichiometric
quantity of methyl ester of trifluoromethane sulphonic
acid, both dissolved in dry dichloromethane, in the
presence of an excess of anhydrous caesium carbonate.
The salt so obtained was treated with a 33% solution of
methanamine in absolute ethanol, then dissolved in
toluene, and the solution of crude base was filtered
off. Purification was carried out chromatographically
(phase: silica gel 60; eluent: toluene/N-methylmetha-
namine = 30/1). The purity of the final product (m.p. =
396–397 K) was checked by TLC, its composition
proved by elemental analysis (% found/theoretical:
C = 81.00/81.05, H = 6.47/6.35, N = 12.43/12,60),
and identity confirmed by X-ray investigations [35].
˚
˚
4.90 A for 3 and 5.15 A for 4 [49]. After each optimi-
zation was completed, the Hessian energy (second
derivatives of the energy as a function of nuclear
coordinates) was calculated and checked for positive
definiteness, in order to assess whether the structures
were true minima [39,50]. The harmonic vibrational
frequencies were subsequently derived on the basis of
the numerical values of these second derivatives
1
[39,50]. H and 13C magnetic shielding tensors (x)
for 1, 2, 3, 4 and 5, as well as TMS were obtained
following the gauge—including atomic orbital
(GIAO) approach [51–53]. The differences between
isotropic magnetic shielding tensors of nuclei in TMS
and the compounds studied (xTMS − x1,2,3,4,5) were
considered to be relevant chemical shifts [51].
2.2. NMR and vibrational spectroscopic
investigations
1H and 13C NMR spectra for saturated solutions of

48
J. Rak et al. / Journal of Molecular Structure 476 (1999) 45–55
All the calculations were conducted on HP/735
amine. The methylamine and dimethylamine groups
in 1 and 4, respectively, are twisted against the acri-
dine moiety; the dimethylamine group in 4 lies per-
pendicular to the acridine moiety, so that the molecule
exhibits cs symmetry. In 2, 3 and 5, which originate
from the imino form, the central ring is more or less
Apollo and IBM/RS 6000 3CT workstations using
GAUSSIAN 92/DFT [54] or GAUSSIAN 94 [55] pro-
gram packages. The dipole moments were extracted
directly from data files following geometry optimiza-
tions. The molecular electrostatic potential around the
molecules was explored using the SPARTAN 4.0 pro-
gram package [56]. Relative atomic partial charges
were determined either on the basis of Mulliken popu-
lation analysis (Mul) [57] or from the fit to the mole-
cular electrostatic potential (MEP fit) at points
selected according to the Besler–Merz–Kollman
scheme [58].
…
folded along the C(9) N(10) axis and the exocyclic
nitrogen atom together with the hydrogen atom (3)
or the methyl group (2 and 5) attached to it is bent
away from the concave side of the acridine nucleus.
Inclusion of the environment in the calculations at
the DFT SCRF level of theory exerts a barely signifi-
cant influence on the geometries of the molecules.
The DFT method, which seems quite reliable in
predicting thermochemical quantities [59], reveals
that the thermodynamically more stable of the tauto-
meric forms 1 and 2 is 1, whereas 2 and 3, being
isomers, exhibit comparable thermodynamic stability
[35]. Of 4 and 5, which retain the respective
constitutions of the amino and imino forms of 9-acri-
dinamine, the former is thermodynamically more
stable.
3. Results and discussion
3.1. Structural and physicochemical features
As our recent X-ray investigations revealed, the
acridine moiety in 4 is almost planar and the dimethy-
lamine group is twisted relative to it through an angle
of 58.6Њ [35]. On the other hand, the central ring in 5 is
As 1 and 2 represent tautomeric forms one can
…
folded along the C(9) N(10) axis through an angle of
predict the equilibrium constant (298KЊ1 2) which,
Y
26.3Њ and the exocyclic nitrogen atom with the
attached methyl group is directed away from the con-
cave side of the acridine nucleus.
Structures of 1, 2, 3, 4 and 5 obtained at the DFT
level of theory are shown in Fig. 1. According to
theoretical predictions, the acridine skeleton is almost
planar in 1 and 4, i.e. in molecules retaining the con-
stitution of the amino tautomeric form of 9-acridin-
according to the data relevant to the DFT level of
theory, is equal to 0.104 [35]. An almost identical
value of this quantity was obtained for the amino Y
imino equilibrium in 9-acridinamine [4].
The dipole moment (Table 1) reflects the nonuni-
form distribution of a charge within the molecule and
to some extent the electrostatic potential around the
molecules. Examination of the latter reveals that two
Table 1
Dipole momentsa and atomic partial charges calculated at the DFT level
Compound no. Dipole moment
Atomic partial charge
(Fig. 1)
Method
C(9)
N(10)
N(23)
C(24);H(24)
C(25);H(25)
1
3.09
3.01
3.89
2.40
3.01
Mul
MEP fit
Mul
MEP fit
Mul
MEP fit
Mul
MEP fit
Mul
MEP fit
0.188
0.269
0.253
0.508
0.242
0.492
0.149
0.583
0.237
0.481
−0.610
−0.676
−0.475
−0.658
−0.651
−0.078
−0.599
−0.736
−0.636
−0.186
−0.573
−0.595
−0.495
−0.453
−0.602
−0.727
−0.499
−0.203
−0.484
−0.463
−0.187
0.172
−0.185
0.045
0.214
0.319
−0.160
−0.186
−0.187
0.060
0.253
0.330
0.252
2
3
4
5
0.358
−0.186
−0.225
−0.160
−0.186
−0.184
−0.210
aDipole moment in D (1D = 3.336 × 10−30 cm).

49
J. Rak et al. / Journal of Molecular Structure 476 (1999) 45–55
zones of potential centred at nitrogen atoms appear in
the molecules. The negative potential region is in the
neighbourhood of the endocyclic nitrogen atom of 1
and 4 (i.e. derivatives from the amino form of 9-acri-
dinamine) and the exocyclic nitrogen atom of 2, 3 and
5 (i.e. derivatives from the imino form of 9-acridina-
mine), while the zone of positive potential occurs at
the exocyclic nitrogen atom of 1 and 4 and the endo-
cyclic nitrogen atom of 2, 3 and 5. This feature is
reflected in the atomic partial charges, derived either
on the basis of Mulliken population analysis (Mul) or
so as to reproduce the molecular electrostatic potential
(MEP fit), shown for selected atoms in Table 1. An
excess negative charge is predicted at both the endo-
cyclic and exocyclic nitrogen atoms. The negative
charge is usually higher at the endocyclic than the
exocyclic N atom in 1 and 4 and at the exocyclic
than endocyclic N atom in 2, 3 and 5. A negative
charge deficiency is always predicted at the C(9)
atom (higher in 2, 3 and 5), whereas at other C
atoms an excess of negative charge is usually
expected. Finally, a negative charge deficiency is
always present at the hydrogen atoms. Nitrogen
atoms may primarily be considered sites of specific
interactions, including the solute solvent or those
leading to the formation of complexes with other
molecules [1,4,60]. It is thus possible that methyl deri-
vatives originating from the amino tautomeric form of
9-acridinamine (1 and 4) behave differently from
those arising from the imino form (2, 3 and 5) in the
presence of macromolecules in living matter.
the absorption corresponding to N(23)H(25), N(10)H(25)
and N(23)H(24) stretching vibrations in 1, 2 and 3,
respectively, is unique. The theoretically predicted
frequencies of this mode in 9-acridinamine [4] and 3
match each other very closely. Moreover, they match
the band observed in the experimental IR spectrum of
9-acridinamine [4]. This could indicate that at least
some 9-acridinamine molecules exist in the imino
tautomeric form.
Investigating the vibrational spectra of 9-acridina-
mine, we noted that the region between 1580–
1680 cm−1, in which bending NH vibrations fall, is
characteristic of both amino and imino forms [4].
We even ascribed bands to given tautomeric forms.
Unfortunately, such an assignment is not feasible in
the case of the N-methyl substituted derivatives of 9-
acridinamine, since bands characteristic of com-
pounds retaining an amino or imino constitution
occur in the same region; hence, these molecules are
indistinguishable (Fig. 2, Table 2). Examination of the
spectra over the whole range of frequencies leaves the
impression that they are specific to a particular mole-
cule and reflect their features and identity. Owing to
the complex nature of these spectra, it is rather seldom
that bands assigned to the same modes of a given type
(amino or imino) of molecules appear at the same
frequencies. It is thus difficult to obtain information
as to the existence of tautomeric phenomena in 9-
acridinamine from only vibrational spectroscopic
investigations.
3.3. NMR investigations
3.2. Vibrational analysis
1
The H NMR spectra of the compounds studied
Infrared and Raman spectra of all the compounds
studied, together with the theoretically determined
vibrational frequencies (scaled), are demonstrated in
Fig. 2. Deformations of the molecules as a whole or
their fragments correspond to 78 (in the case of 1, 2
and 3) or 87 (for 4 and 5) normal modes predicted
theoretically. To permit comparison of characteristic
transitions in which both nitrogen atoms are involved,
we have compiled them in Table 2. IR absorption and
Raman scattering bands generally appear in the
same region in 9-acridinamine, as in its N-methyl
derivatives with ‘blocked’ amino or imino structure.
Appearing at frequencies higher than those character-
istic of any other vibrations in the compounds studied,
consist of a system of signals arising from the eight
aromatic hydrogen atoms: one or two sharp signals
originating from the hydrogen atoms of the methyl
group(s) attached to the nitrogen atom(s) and one
broad signal relevant to the hydrogen atom attached
to the exocyclic or endocyclic nitrogen atom (Fig. 3).
The 13C NMR spectra of the compounds display clear
signals arising from the aromatic and aliphatic carbon
atoms (Fig. 4). As we were unable on the basis of
these spectra to assign signals to particular atoms,
we used HSQC and HMBC (2D spectra are not pre-
sented here) for this purpose. The assignments are
shown in Fig. 3 and Fig. 4, where at all signals the
atoms from which they originate are indicated. These

50
J. Rak et al. / Journal of Molecular Structure 476 (1999) 45–55
Fig. 2. Infrared (IR) and Raman spectra together with the theoretically predicted frequencies ( × 0.96) of vibrational transitions in N-methyl
substituted 9-acridinamine derivatives (numbers in parentheses indicate IR intensities in KM/mol).

51
J. Rak et al. / Journal of Molecular Structure 476 (1999) 45–55
Table 2
Selected bands in the experimental IR and Raman spectra together with harmonic frequencies (cm−1) predicted at the DFT level
Mode
Description
Frequency
IR
Observed
Raman
Assignment
Theoreticala
1
2
3
n1(a)
n13(a)
n14(a)
n15(a)
N(23)H(25) stretching
3443
1617
1600
1547
3244
1613
whole molecule deformation
whole molecule deformation
N(23)H(25) bending
whole molecule deformation
N(23)C(24)H(25) deformation
whole molecule deformation
whole molecule deformation
1611
1559
1559
1520
1411
1354
762
n16(a)
1539
n24(a);n25(a)
n26(a);n27(a)
n52(a)
1412; 1386
1373; 1333
778
1400
1352
n1(a)
n13(a)
n14(a)
n15(a)
N(10)H(25) stretching
C(9)N(23) stretching
N(10)H(25) bending
C(9)N(23)C( 24) deformation
whole molecule deformation
whole molecule deformation
whole molecule deformation
whole molecule deformation
3491
1624
1599
1593
n16(a)
1574
n24(a);n25(a)
n26(a);n27(a)
n52(a)
1396; 1385
1326; 1314
769
n1(a)
n13(a)
n14(a)
n17(a)
n18(a);n19(a)
n20(a);n21(a)
n26(a)
N(23)H(24) stretching
C(9)N(23) stretching
3338
1616
1591
1552
1483; 1475
1458; 1451
1321
3274
1607
1591
1544
1497
1469
3284
1618
1592
1547
whole molecule deformation
whole molecule deformation
whole molecule deformation
C(25)H(26, 27, 28) bending
N(23)H(24) bending
1452
1334
n54(a);n55(a)
whole molecule deformation
740; 735
743
4
n15(aЈ)
n16(aЈ)
n17(aЈ)
n27(aЈ)
n29(aЈ
s-whole molecule deformation
s-whole molecule deformation
s-whole molecule deformation
s-whole molecule deformation
s-C(9)N( 23) stretching; whole molecule
deformation
1619
1599
1538
1416
1387
1624
1612
1554
1409
1374
1555
1409
1375
n60(aЉ);n61(aЉ)
as-whole molecule deformation
758; 750
758
5
n15(a)
n16(a)
n17(a)
n21(a)
n25(a)
n29(a)
n30(a)
n60(a)
C(9)N(23) stretching
1626
1592
1586
1473
1445
1387
1338
739
1618
1597
1616
1596
1581
whole molecule deformation
whole molecule deformation
C(25)H(29, 30, 31) deformation
whole molecule deformation
C(24)H(26, 27, 28) deformation
whole molecule deformation
whole molecule deformation
1484
1462
1384
1362
756
1460
1381
aValues multiplied by 0.96 [4].

52
J. Rak et al. / Journal of Molecular Structure 476 (1999) 45–55

53
J. Rak et al. / Journal of Molecular Structure 476 (1999) 45–55

54
J. Rak et al. / Journal of Molecular Structure 476 (1999) 45–55
assignments are set down with the chemical shifts
predicted by the GIAO method. As can be seen,
both experimental and theoretical 13C chemical shifts
are unique to each molecule investigated and, with
respect to both numerical values and mutual relations,
do not correlate with those found for 9-acridinamine
All the compounds investigated both experimen-
tally and theoretically exhibit unique structural prop-
erties and spectral features. This means that the
replacement of the hydrogen atom(s) attached to the
nitrogen atom(s) by the methyl group(s) is of limited
importance in studies of tautomeric phenomena in 9-
acridinamine. This finding does not conform with our
traditional conviction that ‘blocked’ derivatives retain
all the features of the parent molecules.
The charge distribution and electrostatic potential
in molecules with a ‘blocked’ amino or imino struc-
ture is very similar to that in the parent 9-acridinamine
tautomers. This indicates that zones of positive and
negative potential are located at the exocyclic and
endocyclic nitrogen atoms and that they change
when moving from one tautomer (or its ‘blocked’
derivative) to another. As distribution of the electro-
static potential affects the mode of interaction with
other molecules, the ‘blocked’ compounds can serve
as model derivatives in investigations of interactions
of 9-acridinamine with solvent molecules and macro-
molecules in living matter. Some investigations con-
cerning this problem have already been undertaken by
others [61,62].
1
[4]. The experimental H NMR spectrum of 4 is very
similar to that of 9-acridinamine [4] as regards mutual
relations and the alteration of signals corresponding to
the aromatic hydrogen atoms; however, the chemical
shifts of these are somewhat higher in the case of the
former molecule. On the other hand, the range in
which the aromatic 1H NMR signals appear in all
the other compounds studied is similar to that in 9-
acridinamine, although their mutual relations are dif-
ferent. In all the compounds the signals corresponding
to the hydrogen atoms in methyl groups are sharp, not
split, and appear in regions typical of such atoms. The
1
theoretically predicted H chemical shifts differ from
each other and from those in 9-acridinamine [4]. Two
1
other features are worth mentioning. Firstly, the H
signal originating from the hydrogen atom attached to
the exocyclic nitrogen atom in 3 appears at a relatively
high chemical shift—as was observed and predicted
1
theoretically. Secondly, the shape of the H signals of
the hydrogen atoms in the methyl groups (one or two
sharp signals) indicates that these groups undergo rapid
rotation; in 1 or 4 the whole NH(CH3) or N(CH3)2
groups most probably rotate against the acridine moiety.
Examination of NMR spectra reveals that some of
them are similar (1H NMR spectrum of 4) to the
corresponding ones for 9-acridinamine (amine tautomer
[4]) but others are not. This means that it is not generally
Acknowledgements
The authors thank Dr P. Sowin´ski for his help in the
NMR studies. The financial support of this work from
the Polish State Committee for Scientific Research
(KBN) under Grants 2 P303 058 06 (Contract No.
PB-0593/P3/94/06) and BW/8000-5-0355-7 is grate-
fully acknowledged.
1
possible to ascribe H and 13C signals to given tauto-
meric forms and implies that NMR spectra reflect the
unique features of the molecules investigated.
References
[1] J. Rak, J. Blazejowski, R.J. Zauhar, J. Org. Chem. 57 (1992)
3720.
4. Final remarks
[2] J. Rak, J. Blazejowski, J. Photochem. Photobiol. A.: Chem. 67
(1992) 287.
[3] J. Rak, P. Skurski, L. Jozwiak, J. Blazejowski, Aust. J. Chem.
50 (1997) 97.
[4] J. Rak, P. Skurski, M. Gutowski, L. Jozwiak, J. Blazejowski, J.
Phys. Chem. A 101 (1997) 283.
[5] L. Jozwiak, P. Skurski, J. Rak, J. Blazejowski, Spectrochim.
Acta A 53 (1997) 1723.
One derivative of 9-acridinamine with fixed amino
constitution (4) and two more with retained imino (3
and 5) structures were synthesized and examined by
IR, Raman and NMR spectroscopy. A fourth com-
pound obtained can exist in two tautomeric forms (1
or 2); this was suggested by theoretical studies, as well
as analyses of NMR and to some extent vibrational
spectra.
[6] A.V. Karyakin, A.M. Grigorovskii, N.G. Yaroslavskii, Dokl.
Akad. Nauk SSSR 67 (1949) 679.

55
J. Rak et al. / Journal of Molecular Structure 476 (1999) 45–55
[7] R.M. Acheson, M.L. Burstall, C.W. Jefford, B.F. Sansom, J.
Chem. Soc. (1954) 3742.
[8] A.V. Karyakin, A.V. Shablya, Dokl. Akad. Nauk SSSR, Ser.
Khim. 116 (1957) 969.
[40] J. Baker, J. Comput. Chem. 7 (1986) 385.
[41] H.B. Schlegel (Ed.), Modern Electronic Structure Theory:
Geometry Optimization on Potential Energy Surfaces, World
Scientific, Singapore, 1994.
[9] A.C. Capomacchia, J. Casper, S.G. Schulman, J. Pharm. Sci.
63 (1974) 1272.
[10] A.C. Capomacchia, S.G. Schulman, J. Pharm. Sci. 64 (1975)
1256.
[11] L.N. Short, J. Chem. Soc. (1952) 4584.
[12] Z.V. Pushkareva, Z.Yu. Kokoshko, Dokl. Akad. Nauk SSSR
93 (1953) 77.
[13] A.K. Sukhomlinov, Zh. Obshch. Khim. 28 (1958) 1038.
[14] Yu.N. Sheinker, E.M. Pieresleni, Dokl. Akad. Nauk. SSSR,
Ser. Khim. 131 (1960) 1366.
[15] J.P. Kokko, J.H. Goldstein, Spectrochim. Acta 19 (1963) 1119.
[16] F.N. Li, O.G. Rodin, V.V. Redchenko, V.F. Traven, Zh.
Obshch. Khim. 61 (1991) 186.
[17] A. Albert, The Acridines, 2nd ed., Edward Arnold, London,
1966.
[42] M.M. Francl, W.J. Pietro, W.J. Hehre, J.S. Binkley, M.S.
Gordon, D.J. DeFrees, J.A. Pople, J. Chem. Phys. 77 (1972)
3654.
[43] P.C. Hariharan, J.A. Pople, Theor. Chim. Acta 28 (1973) 213.
[44] A.D. Becke, Phys. Rev. A 38 (1988) 3098.
[45] A.D. Becke, J. Chem. Phys. 98 (1993) 1372, 5648.
[46] C. Lee, W. Yang, R.G. Parr, Phys. Rev. B 37 (1988) 785.
[47] H.S. Rzepa, Y.Y. Man, M.M. Karelson, M.C. Zerner, J. Chem.
Soc., Perkin Trans. 2 (1991) 635.
[48] M.W. Wong, K.B. Wiberg, M.J. Frisch, J. Am. Chem. Soc.
114 (1992) 523, 1645.
[49] J.B. Foresman, A. Frisch, Exploring Chemistry with Electro-
nic Structure Methods: A Guide to Using Gaussian, Gaussian,
Pittsburgh, PA, 1993.
[50] N.C. Handy, D.J. Tozer, G.J. Laming, C.W. Murray, R.D.
Amos, Isr. J. Chem. 33 (1993) 331.
[51] R. Ditchfield, Mol. Phys. 27 (1974) 789.
[18] R.M. Acheson, Acridines, 2nd ed., Interscience, New York,
1973.
[19] L.S. Lerman, J. Mol. Biol. 3 (1961) 18.
[20] A. Orgel, S. Brenner, J. Mol. Biol. 3 (1961) 762.
[21] B. Pullman, Compt. Rend. 255 (1962) 3255.
[22] A. Kellmann, J. Phys. Chem. 81 (1977) 1195.
[23] G. Duportail, Y. Maussa, J. Chambron, Biopolymers 16 (1977)
1397.
[24] Y. Kubota, Y. Motoda, J. Phys. Chem. 84 (1980) 2855.
[25] L.A. Diverdi, M.R. Topp, J. Phys. Chem. 88 (1984) 3447.
[26] M. Wirth, O. Buchardt, T. Koch, P.E. Nielsen, B. Norden, J.
Am. Chem. Soc. 110 (1988) 932.
[27] Y. Baba, A. Kunihiro, A. Kagemoto, Thermochim. Acta 202
(1992) 241.
[28] G. Albiser, Compt. Rend., Ser. III 315 (1992) 265.
[29] M.E. Nuss, F.J. Marsh, P.A. Kollman, J. Am. Chem. Soc. 101
(1979) 825.
[52] K. Wolinski, J.F. Hinton, P. Pulay, J. Am. Chem. Soc. 112
(1990) 8251.
[53] J. Gauss, J. Chem. Phys. 99 (1993) 3629.
[54] M.J. Frisch, G.W. Trucks, H.B. Schlegel, P.M.W. Gill, B.G.
Johnson, M.W. Wong, J.B. Foresman, M.A. Robb, M. Head-
Gordon, E.S. Replogle, R. Gomperts, J.L. Andres, K. Ragha-
vachari, J.S. Binkley, C. Gonzales, R.L. Martin, D.J. Fox, D.J.
DeFrees, J. Baker, J.J.P. Stewart, J.A. Pople, Gaussian 92/
DFT, Revision F.2, Gaussian, Pittsburgh, PA, 1993.
[55] 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. Peters-
son, 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.J.P. Stewart, M. Head-Gordon, C.
Gonzales, J.A. Pople, Gaussian 94, Revision B.2, Gaussian,
Pittsburgh, PA, 1995.
[56] Available from Wavefunction, 8401 Von Karman, Suite 370,
Irvine, CA 92715, USA.
[57] R.S. Mulliken, J. Chem. Phys. 23 (1955) 1833, 1841.
[58] B.H. Besler, K.M. Merz, P.A. Kollman, J. Comput. Chem. 11
(1990) 431.
[59] B.G. Johnson, P.M.W. Gill, J.A. Pople, J. Chem. Phys. 98
(1993) 5612.
[60] D. Hadzi, J. Koller, M. Hodoscek, D. Kocjan, in: Z.B. Maksic
(Ed.), Modeling of Structure and Properties of Molecules, Ellis
Harwood, London, 1987.
[30] K.J. Miller, Macromolecules 17 (1984) 1709.
[31] S. Grzesiak, H. Otto, N.A. Dencher, Biophys. J. 55 (1989)
1101.
[32] P. Proks, T. Hianik, P. Kvasnicka, Gen. Physiol. Biophys. 11
(1992) 441.
[33] N.S. Drozdov, O.M. Cherntzov, Zh. Obshch. Khim. 5 (1935)
1576, 1736.
[34] D.J. Dupre, F.A. Robinson, J. Chem. Soc. (1945) 549.
[35] J. Rak, K. Krzyminski, P. Skurski, L. Jozwiak, A. Konitz, P.
Dokurno, J. Blazejowski, Aust. J. Chem., in press.
[36] A. Albert, B. Ritchie, J. Chem. Soc. (1943) 458.
[37] J. Rulewski, K. Krzyminski, A. Konitz, P. Dokurno, J. Rak, J.
Blazejowski, Mol. Cryst. Liq. Cryst. 276 (1996) 91.
[38] R. Croasman, R.M.K. Carlson, Two-Dimensional NMR Spec-
troscopy: Applications for Chemists and Biochemists, 2nd ed.,
VCH, New York, 1994.
[61] Y. Mandi, K. Regely, I. Ocsovszky, J. Barbe, J.P. Galy, J.
Molnar, Anticancer Res. 14 (1994) 2633.
[39] J.K. Labanowski, J.W. Andzelm (Eds.), Density Functional
Methods in Chemistry, Springer Verlag, New York, 1991.
[62] I.B. Petri, I. Berek, A.-M. Galy, J. Barbe, L. Berek, J. Molnar,
Acta Microbiol. Immunol. Hung. 42 (1995) 203.