Studies on electron spin resonance spectroscopy of biradical molecules containing 14N-O and 15N-O moieties

Article abstract of DOI:10.1016/j.saa.2007.09.037

The biradicals with ¹⁴N-Oxide and ¹⁵N-Oxide at the both ends of a molecule are synthesized for the molecular ruler of protein structure, and a potential device for quantum computing. We also establish a general synthetic method for reliable biradical formation. ESR spectra are recorded for the biradicals containing ¹⁵N-Oxide and ¹⁴N-Oxide with various interdistance separations. We find that two types of biradicals yielded different ESR spectra depending upon the distance between the ¹⁵N-O and ¹⁴N-O moieties in a molecule. This is due to electron spin dipole-dipole interaction occurring between the radicals. We also find that there is an indication of isotopic nuclear effects in the dipole-dipole interactions. The present study implies feasibility of the distance measurement between two different N-Oxides containing ¹⁴N and ¹⁵N isotopes. We conclude that quantum entanglement effects are observed through the dipolar interactions, which enable application of quantum computing devices operating in the liquid state.

Full text of DOI:10.1016/j.saa.2007.09.037

Available online at www.sciencedirect.com
Spectrochimica Acta Part A 69 (2008) 1367–1371
Studies on electron spin resonance spectroscopy of biradical molecules
containing 14N-O and 15N-O moieties
Hiromi Kameyab, Hideo Nakamuraa,∗, Mitsuko Ukaia, Yuhei Shimoyamab
a Department of Chemistry, Hokkaido University of Education, 040-8567 Hakodate, Japan
b Soft Matter Physics Laboratory, Graduate School of Emergent Functional Science, Muroran Institute of Technology, Muroran 050-8585, Japan
Received 6 August 2007; accepted 17 September 2007
Abstract
The biradicals with 14N-Oxide and 15N-Oxide at the both ends of a molecule are synthesized for the molecular ruler of protein structure, and a
potential device for quantum computing. We also establish a general synthetic method for reliable biradical formation. ESR spectra are recorded
for the biradicals containing 15N-Oxide and 14N-Oxide with various interdistance separations. We find that two types of biradicals yielded different
ESR spectra depending upon the distance between the 15N-O and 14N-O moieties in a molecule. This is due to electron spin dipole–dipole interaction
occurring between the radicals. We also find that there is an indication of isotopic nuclear effects in the dipole–dipole interactions. The present
study implies feasibility of the distance measurement between two different N-Oxides containing 14N and 15N isotopes. We conclude that quantum
entanglement effects are observed through the dipolar interactions, which enable application of quantum computing devices operating in the liquid
state.
© 2007 Elsevier B.V. All rights reserved.
Keywords: Biradical; Electron spin resonance; N-Oxide; Aromatic dicarboxylic acid type radical; Urea type radical
15N-Oxide moieties differ are needed for distance information
measurement of biomolecules [1]. Hence, we aimed to establish
a simple synthetic method which can vary the distance and the
direction between radicals in a biradical compound.
1. Introduction
Biradical compounds have two unpaired electrons in the same
molecule. Various biradical compounds containing N-Oxides
have been reported [1–3]. Biradicals are employed as spin label
agents in the life science, oxidizing agents in the organic chem-
istry and organic magnetic materials in physics [4]. There is
an existing method of synthesizing two 14N-Oxides simultane-
ously, attached to an ester which provides the basic frame parts.
On the other hand, biradicals of ring structure, like the adaman-
tane types are generated by synthesizing two basic frames with
an N-Oxide each [5–7].
The present study aims at the synthesis of biradical com-
pounds applicable to life science and quantum computing. In
quantum computers, it is necessary to make input and out-
put terminals independent and to discriminate between them.
Therefore, the target biradical compound has 14N-Oxide and
15N-Oxide moieties in the same molecule. In life science, how-
ever, compounds where the distance between the 14N-Oxide and
In order to fulfill these purposes, known biradicals have three
problems. (1) Both N-Oxides in the same molecule are 14N (nat-
ural abundance 99.6%). An adamantine type compound cannot
be used to synthesize other compounds where the distance and
direction can be changed by the same synthetic method [4–7].
(2) A straight chain can change the distance between N-Oxides
by the existing synthetic method [1]. However, in a straight chain
the distance cannot be determined, as a result of the rotational
isomers of the carbon chains. (3) Transesterification occurs in
ester bond. From these problems, a biradical compound fulfill-
ing two conditions is considered as the fundamental indicator of
a synthetic method. One of the conditions is that the biradical
compound should have a 14N-Oxide and 15N-Oxide in the same
molecule. Another condition is to have a biradical where the
distance between the N-Oxides can vary.
The reason for using amide bonds is that the target biradi-
cal compounds have a 14N-Oxide and 15N-Oxide in the same
molecule. 14N and 15N are core isotopes. If transesterification
happens, a biradical compound containing a 14N-Oxide and 14N-
∗
Corresponding author.
E-mail address: hnaka@cc.hokkyodai.ac.jp (H. Nakamura).
1386-1425/$ – see front matter © 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2007.09.037

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H. Kameya et al. / Spectrochimica Acta Part A 69 (2008) 1367–1371
Oxide, or 15N-Oxide and 15N-Oxide can be resulted by the
reaction. On the other hand, we considered a combination of
a basic frame and an amine, using an amide bond. Amide bonds
are the molecular structures that are used for proteins or peptides.
Since they are more stable than ester bonds, transesterification
does not occur. Reaction conditions including a strong acid or
strong base are required for cleavage of an amide bond. So, they
do not cleave under ESR measurement conditions. When intro-
duced into biomolecules, the cleavage and joint position does
not change simply, either. It is necessary to use an amine which
can be purchased containing both 14N and 15N for the amide
bonds. Therefore, 1-14N-4-amino-2,2,6,6-tetramethylpiperidine
and 1-15N-4-amino-2,2,6,6-tetramethylpiperidine were used as
moieties containing a nitroxide. Furthermore, the technique to
form peptide bonds was used. Dicyclohexylcarbodiimide (DCC)
and 1-hydroxy-1H-benzotriazole (HOBt) are peptide bond
condensing agents that have been used for many years. 4-(4,6-
Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride
(DMT-MM) is a new condensing agent which can be used
in polar solvents like alcohol [8–12]. A synthetic process
was examined using many condensing agents besides these
(Fig. 1).
The reason for using an aromatic dicarboxylic acid for the
frame portion: In the present study, variable distance and direc-
tion between the 14N-Oxide and 15N-Oxide moieties is the aim
for the generation of various biradical compounds. Therefore,
an aromatic dicarboxylic acid was used for the basic frame por-
tion. As a result, the distance and direction between the biradical
moieties can be changed by changing the joint position of the
two carboxylic acid groups on the basic frame, while using the
same synthetic method. Varying the central number of aromatic
rings can also make the distance between nitroxide variables
(Fig. 2).
Fig. 1. Various type of biradical compounds thus far reported.
and 15N-Oxide at both ends of a molecule from 4-amino-
2,2,6,6-tetramethylpiperidineandanaromaticdicarboxylicacid.
Furthermore, we defined ESR parameters such as D and J terms
for the distant measurement as well as the spin exchange rate
(Fig. 3).
2. Experimental
2.1. Synthesis
The chlorine of 1 was first replaced with amine 5 to give 2
in 36% yield. Replacement of the PhO group of 2 with amine
5-15N afforded urea 3 in 66% yield. Biradical 4 was obtained by
oxidation with m-chloroperbenzoic acid in 95% yield (Fig. 4).
In the present study, we aim at a general synthetic
method for biradical compounds that have a 14N-Oxide
Fig. 2. The biradical compounds with aromatic carboxylic acid.

H. Kameya et al. / Spectrochimica Acta Part A 69 (2008) 1367–1371
1369
the X-band (9.3 GHz). The microwave field strength was varied
from 0 to 64 mW. Magnetic field modulation was operated at
100 kHz. The solvent in the present study is dichloromethane
for the all the ESR measurements. All the measurements were
made at room temperature (approximately 20 ◦C).
3. Results
3.1. Synthesis
We established a general synthetic method for biradical com-
pounds containing a 14N-Oxide and 15N-Oxide in the same
molecule.
The synthetic method for urea type molecules is as
follows. The chlorine of chloride 1 was first replaced
with 4-amino-2,2,6,6-tetramethylpiperidine-14N 5 to give the
amide compound 2 in 36% yield. Replacement of the PhO
group of the generated compound 2 with 4-amino-2,2,6,6-
tetramethylpiperidine-15N 5-15N afforded urea compound 3 in
66% yield. Biradical compound 4 was then obtained by oxida-
tion with m-chloroperbenzoic acid in 95% yield (Scheme 1).
The general synthetic method for aromatic diamides was
studied using 1,4-dicarboxylic acid. Half-ester 6 and amine 5
were coupled with DMT-MM to give monoamide 7 in 63% yield.
Hydrogenation of 7 with Pd-C afforded the carboxylic acid in
33% yield. Condensation of the carboxylic acid and amine 5-
15NwithDMT-MMaffordedthediamide8in87%yield. Finally,
biradical compound 9 was obtained by oxidation of diamide 8
with m-chloroperbenzoic acid in 73% yield (Scheme 2).
Fig. 3. An ESR spectrum of aromatic diamide-type compound with 14N- and
15N-Oxides.
3.2. ESR spectral analysis
ESR spectral measurements were carried out on the urea
type and the aromatic diamide type biradicals generated by
the synthetic procedures described above. The analysis of the
ESR spectra revealed the magnetic interaction parameters of the
two biradical molecules (Table 1). In the urea type, the nuclear
coupling constant a was as follows. It was a = 1.41 mT in the
14N-Oxide, and a = 1.93 mT in the 15N-Oxide. The exchange
interaction was J = 13.6 (MHz). The D-term of 14N-Oxide and
15N-Oxide were found to be 30.6 and 10.8 MHz for urea and
diamide types, respectively. These values remain constant irre-
spective of 14N-Oxide and 15N-Oxide moieties. This is due
to the distance dependency of the D-term. By comparing the
obtained a and J, it became apparent that J < a. From this
result, and since only a short distance exists between the two
N-Oxides, the urea type biradical compound has a strong dipole
Fig. 4. An ESR spectrum of urea-type compound with 14N- and 15N-Oxides.
Synthesis of biradical 9 having the aromatic diamide moi-
ety was as follows. Half-ester 6 and amine 5 ware coupled with
DMT-MM to give monoamide 7 in 63% yield. Hydrogenation of
7 with Pd-C afforded the carboxylic acid in 33% yield. Conden-
sation of the carboxylic acid and amine 5-15N with DMT-MM
afforded the diamide 8 in 87% yield. Finally biradical 9 was
obtained by oxidation of 9 with m-chloroperbenzoic acid in 73%
yield.
2.2. ESR spectroscopy
ESR measurements were carried out using an ESR spectrom-
eter (JEOL, JES-FEIXG). All the ESR spectra were recorded at
Scheme 1. Preparation of urea derivative 4. (a) 4-amino-2,2,6,6-tetramethylpiperidine 5, NaOH, H2O, Et2O, 36%; (b) 4-amino-2,2,6,6-tetramethylpiperidine-15
5-15N, NaOH, H2O, THF, 66%; (c) m-chloroperbenzoic acid, 95%.
N

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Scheme 2. Preparation of 1,4-dicarboxylic acid diamide 9. (a) 4-amino-2,2,6,6-tetramethylpiperidine 5, DMT-MM, CH3OH, 63%; (b) H2, Pd-C, EtOH, 33%; (c)
4-amino-2,2,6,6-tetramethylpiperidine-15N 5-15N, DMT-MM, CH3OH, 87%; (d) m-chloroperbenzoic acid, 73%.
Table 1
ent directions and distances between the N-Oxide moieties can
be synthesized easily by the same compounding method. 4-(4,6-
Parameters of magnetic interaction for various nitroxide compounds
Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride
(DMT-MM), which is a new condensing agent developed in
recentyears, hasthreeoutstandingpointsascomparedwithother
condensing agents [4–8]. (1) Polar solvents, such as alcohol,
can be used. (2) It is not hygroscopic and is stable. (3) Reaction
operation is very easy. The one-step operation of adding DMT-
MM, an amine and a substrate which has a carbonyl group can
generate an amide combination. There are condensing agents
such as DCC and HOBt which have been known for many
years. DCC and HOBt require complicated synthetic operations
and after-treatment compared with DMT-MM. The execution
of the condensation reaction became easy compared with for-
mer procedures, because using DMT-MM raises the solubility
of substrate, and is easily handled.
Nitroxide compounds a (mT) g-value D (MHz)
J (MHz)
Urea
14N-Oxide
15N-Oxide
1.41
1.93
2.002
2.001
30.0
10.8
13.6
Arometic diamide
14N-Oxide
15N-Oxide
1.44
2.03
2.005
2.005
0
interaction. In the aromatic diamide, was a = 1.44 mT in the 14N-
Oxide, anda = 2.03 mTinthe 15N-Oxide. Jwas J = 0 MHz. From
these results, since there is a long distance between the two N-
Oxides, the aromatic diamide biradical compound is in a state
in which a dipole interaction can almost be disregarded. In case
of short distance between the two N-Oxides, the dipole inter-
action becomes stronger. However, it turns out that this can be
mostly disregarded over a longer distance. It is possible to mea-
sure the distance between the 14N-Oxide and 15N-Oxide from
the difference in the exchange interaction in the ESR spectrum.
Therefore, we find that the distance between two spin labels in
a molecule is able to be measured from the ESR spectrum.
4.2. Physical interaction in biradical
The hyperfine coupling constant of the 14N-Oxide and 15N-
Oxide in the present study (Table 1) was 1.41 and 1.93 mT,
respectively. However, the similar biradical with the homo-
geneous moieties 14N-Oxide and 14N-Oxide in the aqueous
solution yielded 4.8 mT (17.1GHz)[13]. The discrepancy is due
to the interaction between 15N-Oxide and 14N-Oxide moieties,
in other words isotope effects. The J-value in the present study
was 13.6 MHz. This value is compared with 65 and 56 MHz
in the similar biradical in the aqueous solution and in the SDS
micelle solution, respectively [13]. The difference in the J-value
might be attributable to the distance between the moieties.
4. Discussion
4.1. Synthesis of biradicals
The present study has two outstanding points as compared
with the composition of biradical compounds which have thus
far been reported. An aromatic dicarboxylic acid was used as the
substrate in this research. This molecule has two carbonyl groups
on an aromatic ring. It is possible that the composition of birad-
ical compounds in which the direction and distance between the
N-Oxide moieties differ can be synthesized by using a substrate
in which the joint positions of the carbonyl groups differ. In this
research, the central compounding method for biradical com-
pounds having both a 14N-Oxide and 15N-Oxide in the same
molecule was established. By using this compounding method,
aromatic diamide type biradical compounds which have differ-
5. Conclusions
1. Biradical compounds which differ in the direction and dis-
tancebetweentheir 14N-Oxideand 15N-Oxide moietiesinthe
same molecule were generated, and a general composition
method for an aromatic diamide type biradical compound
was established.

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1371
2. From the ESR spectra of both the urea type and the aromatic
diamide type biradical compound, the distance between the
14N-Oxide and 15N-Oxide moieties were checked and corre-
lated with features of the ESR spectrum.
3. It is possible to perform distance measurements between
N-Oxides from spectrum changes by measuring biradical
compounds which differ in distance between their N-Oxide
biracial by ESR.
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