From virtual to physical: Integration of chemical logic gates

Article abstract of DOI:10.1002/anie.201104228

Integration by parts: Advanced information processing at the molecular level requires integrated logic gates, which has to date been possible only virtually. Now, two independently working AND molecular logic gates are brought together by "click" chemistry to form integrated logic gates which respond exactly as predicted from such an integration scheme (see picture, EET=excitation energy transfer). Copyright

Full text of DOI:10.1002/anie.201104228

Communications
DOI: 10.1002/anie.201104228
Chemical Logic Gates
From Virtual to Physical: Integration of Chemical Logic
Gates**
Ruslan Guliyev, Seyma Ozturk, Ziya Kostereli, and Engin U. Akkaya*
Angewandte
Chemie
9826
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 9826 –9831

Logic gates are fundamental building blocks of silicon
circuitry. Current technology used in integrated circuit
design is fast approaching its physical limits, and this
“impending doom” scenario[1] has led many to consider
potential alternatives in information processing. Bottom-up
approaches, including molecular mimicry of logic gates with
ion-responsive molecules, have received considerable atten-
tion since 1993, following the pioneering work of de Silva
et al.[2] In nearly two decades, all 16 fundamental logic gates[3]
and higher functions such as half-adder/subtractor,[3,4] multi-
plexer,[5] password protection,[6] encoder/decoder,[7] and
sequential logic[8] were demonstrated. These higher functions
require considerable degrees of integration or concatenation
between logic gates if they are to be implemented using
standard practice of semiconductor technology. We also
appreciate the fact that molecular logic need not be confined
within the reigning paradigms of silicon-based information
processing. Nevertheless, physical integration of chemical
(molecular) logic gates is especially important for rational
design and implementation towards advanced molecular-
scale computing. However, with chemical logic gates, almost
all of the integration or concatenation is “functional”. In
other words, the outputs at various channels (for example, at
different wavelengths) are typically analyzed, and a con-
catenated set of logic gates is then proposed to be acting on
the inputs to generate the apparent output sequence. A more
fitting term for this class of integration might be “virtual”.
While this approach is highly convenient and reconfigurable/
superposed logic gates can be quite useful, it is nevertheless
obvious that, at some point, there has to be simple and general
methodologies for physically (as opposed to virtually) bring-
ing together independently working molecular logic gates to
function together as concatenated/integrated logic gates.
Previous work toward concatenated logic gates was often
based on enzymatically coupled systems.[9] While these
systems involve interesting reinterpretations or rewiring of
enzymatic pathways and other biomolecular interactions, we
will need to have more general and broadly applicable
methodologies for de novo concatenation on the way to more
capable integrated systems.
linked to a ruthenium complex, resulting in a serial con-
nection between two logic operations. However, clear dem-
onstration (with non-additive inputs and large digital-on-off
changes) of independently existing and functional logic gates,
physically coupled together and thus functioning in an
integrated fashion, remained elusive.
Herein, we propose two possible ways of achieving
integration of independently functioning chemical logic
gates: one approach makes use of the inner filter effect
(IFE), which is modulated photochromically, and the other
one is based on increased efficiency of Fçrster type intra-
molecular energy transfer (excitation energy transfer, EET)
compared to the intermolecular energy transfer (other factors
remaining unchanged). Utility of IFE in molecular logic was
shown earlier;[11] in that work distinct compartmentalization
of the logic molecules was needed, and this was achieved on a
macroscopic level by placing them in separate cuvettes. In our
IFE-based approach, we chose thionine as the photochromic
agent (Scheme 1). Thionine, although not utilized in any logic
gate design to date, could be highly useful in optical
Scheme 1. Reversible photochemical conversion of thionine into the
leucothionine form. DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone.
concatenation of logic gates. Thionine in the purple-colored
solution (absorption maximum at 590 nm) can be photo-
chemically reduced by many mild reducing agents, such as
sodium ascorbate, to yield the colorless leuco form. The clear
solution with a higher transmittance (Figure 1) will allow
sufficient intensity of light at another wavelength (560 nm) to
interrogate the second logic gate (and serve as an input)
present in the same solution.
Herein, the first independent AND logic gate is the
thionine molecule: the output is the transmitted monochro-
matic light at 560 nm. This output will be high only if both
photonic inputs, that is, broadband white light and 560 nm
light, are introduced to the system. (Figure 2). The other
AND logic gate we propose in this scheme is related to
compound 2 (Scheme 2). It is a styryl-bodipy derivative with a
dipicolylamine (DPA) group tethered at the meso-(8) posi-
tion. Its fluorescence is quenched through an efficient photo-
induced electron transfer (PeT) process, but high emission
intensity is recovered when certain metal ions such as ZnII are
added. Both inputs (light at 560 nm and ZnII ions) need to be
high for output to be high (1). Naturally, this second AND
gate works independently as well. When we bring together
these two gates in solution, the output of the first gate
(thionine) will be one of the inputs of the gate 2. Thus, in the
mixture of two AND logic components, the two gates are
integrated through photochemical modulation of the inner
filter effect. Reversibility of the photochromic response was
clearly demonstrated (Figure 3). It is also important to show
In recent years, a few examples of chemical cascading, or
integration schemes, were proposed.[10] In a promising recent
report by the Raymo and Credi groups,[10c] a merocyanine
derivative that photochemically produces hydrogen ions was
[*] R. Guliyev,[+] Prof. Dr. E. U. Akkaya
UNAM-Institute of Materials Science and Nanotechnology
Bilkent University, Ankara 06800 (Turkey)
E-mail: eua@fen.bilkent.edu.tr
S. Ozturk,[+] Z. Kostereli,[+] Prof. Dr. E. U. Akkaya
Department of Chemistry
Bilkent University, 06800 Ankara (Turkey)
[+] These authors contributed equally to this work.
[**] We are grateful for funding by Turkish Academy of Sciences (TUBA)
and State Planning Organization (DPT). R.G. and S.O. thank
TUBITAK for graduate scholarships. We also thank Bora Bilgic for
his creative graphics contributions.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201104228.
Angew. Chem. Int. Ed. 2011, 50, 9826 –9831
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 9827

Communications
Figure 2. Operation of the integrated logic gates (IFE) as demon-
strated by the emission spectra of compound 2 (2.2 mm) in the
presence of thionine/leucothionine (12.5 mm) in methanol. a) 2 alone,
b) 2+ZnII, c) 2+thionine, d) 2+leucothionine ((c)+white light),
e) 2+thionine+ZnII, f) 2+leucothionine+ZnII ((e)+white light). ZnII
ions were added in the form of perchlorate salt at 22.0 mm concen-
tration. lex =560 nm, slit width=5 nm.
Figure 1. Top: Transmission spectra of thionine (red, solid curve) and
leucothionine (black, dashed curve) 12.5 mm in methanol. The leuco
form was obtained by exposing the thionine solution to broadband
white light in the presence of sodium ascorbate as a reducing agent.
Bottom: A representation of the operation of the coupled AND logic
gates in the IFE integration scheme.
Scheme 2. Synthesis of logic-gate modules and the final click reaction for the integrated logic compound 8. TFA=trifluoroacetic acid,
TCQ=2,3,5,6-tetrachloro-1,4-benzoquinone.
9828 www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 9826 –9831

Figure 4. Absorbance spectra of Compound 8 (3.0 mm) in acetonitrile
in the presence of ZnII and HgII cations (20.0 and 10 mm, respectively).
a) 8, b) 8+ZnII, c) 8+HgII, d) 8+ZnII +HgII.
Figure 3. Reversibility of the thionine photochromic response. The
reduced leuco form of thionine (12.5 mm), which is produced by
photochemical reduction, can be transformed back to the original
chromophore by DDQ oxidation. The reduction–oxidation cycling can
be repeated many times in the presence of the second logic compound
2 (2.2 mm).
that with broadband white light alone, the emission from the
gate 2 (styryl-bodipy) has to be low, and this result has been
demonstrated as well. On standing at room temperature in
the presence of excess ascorbate, the oxidized form can be
accessed by the addition of DDQ or by air oxidation. It is
interesting to note that DDQ and ascorbate do not react
directly under the conditions of the study. In summary, two
independent AND logic gates can be coerced to work in an
integrated fashion by simply mixing them in solution.
The idea of using excitation energy transfer for the
integration of logic gates was proposed in a conjectural
article.[12] In our energy transfer (EET) based approach
however, two chemical gates were again designed to act
separately and independently as two distinct AND gates,
without interference or cross-talk. The design of these
chemical logic-gate molecules includes “clickable” azide
and terminal alkyne units. The first AND gate is the same
as the second one used in the previous scheme (compound 2).
The other is also a monostyryl derivative (7), but since it has
an azathiacrown moiety attached through its amine nitrogen
atom (essentially a dialkylamino group), increased charge-
transfer characteristics lead to longer-wavelength absorption
and emission (Figure 4). Compound 7 also acts as an AND
logic gate, with a photonic (light at 580 nm) and ionic (HgII)
input. Only when both inputs are present is strong red
emission at 660 nm produced. When compounds 2 and 7 are
“clicked” together with Huisgen cycloaddition, the obtained
product (8) is in fact an ion-modulated energy-transfer
cassette. In this molecule, the photonic output at 660 nm is
only generated when all three inputs (hn l = 560 nm, ZnII, and
HgII) are present (high). In all other combinations, the
emission at 660 nm is low (Figure 5). The emission at the red
channel is dependent on the PeT efficiency of the module
derived from the first logic gate (2). The excitation at 560 nm
results in excitation of that particular fluorophore, but in the
absence of ZnII, energy transfer efficiency is drastically
reduced. When ZnII is present, PeT is blocked, and excitation
Figure 5. Operation of the integrated logic gates (EET) as demon-
strated by the emission spectra of compound 8 (3.0 mm) in acetonitrile
in the presence of ZnII and HgII cations (20.0 and 10 mm, respectively).
lex =560 nm, slit width=5–2.5 nm. a) 8@560 nm, b) 8@640 nm;
c) 8@680 nm; d) 8+HgII@560 nm; e) 8+ZnII@560 nm;
f) 8+HgII +ZnII@560 nm.
energy is transferred to the second module. This energy
transfer is evidenced both by quantum yield (2 vs. 8, the donor
data) and lifetime changes (Table 1). The emission quantum
yield of the donor module 2 is 0.1 (due to effective PeT), but
increases to 0.71 on ZnII addition. In the “click” integrated
logic molecule 8, the donor is hardly emissive (FF = 0.002,
owing to effective Fçrster type energy transfer). The second
module (acceptor) derived from compound 7, even when
energy transfer is effective, does not fluoresce brightly
because of strong intramolecular charge transfer charge-
donor characteristics of the dialkylamino group. When the
final input (HgII) is added, then strong red emission is
observed (Figure 5).
Since the ligands in both of the logic gate modules are
highly selective, there is no crosstalk; the metal ions do not
interfere or target the “wrong” ligand at the concentrations of
the study, at least to an extent to cause problems in signal
Angew. Chem. Int. Ed. 2011, 50, 9826 –9831
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 9829

Communications
Lynch, K. R. Nesbitt, S. T. Patuwathavithana, N. L. D. S. Ramya-
lal, J. Am. Chem. Soc. 2007, 129, 3050 – 3051; f) A. P. de Silva, S.
Uchiyama, Nat. Nanotechnol. 2007, 2, 399 – 410; g) M. Yuan, W.
Zhou, X. Liu, M. Zhu, J. Li, X. Yin, H. Zheng, Z. Zuo, C.
Ouyang, H. Liu, Y. Li, D. Zhu, J. Org. Chem. 2008, 73, 5008 –
5014; h) K. Szacilowski, Chem. Rev. 2008, 108, 3481 – 3548; i) N.
Kaur, N. Singh, D. Cairns, J. F. Callan, Org. Lett. 2009, 11, 2229 –
2232; j) H. Komatsu, S. Matsumoto, S. Tamaru, K. Kaneko, M.
Ikeda, I. Hamachi, J. Am. Chem. Soc. 2009, 131, 5580 – 5585;
k) S. Ozlem, E. U. Akkaya, J. Am. Chem. Soc. 2009, 131, 48 – 49;
l) J. Andreasson, U. Pischel, Chem. Soc. Rev. 2010, 39, 174 – 188.
[4] a) A. P. de Silva, N. D. McClenaghan, J. Am. Chem. Soc. 2000,
122, 3965 – 3966; b) S. J. Langford, T. Yann, J. Am. Chem. Soc.
2003, 125, 11198 – 11199; c) W. Jiang, H. Zhang, Y. Liu, Front.
Chem. China 2009, 4, 292 – 298; d) D. Margulies, G. Melman,
C. E. Felder, R. Arad-Yellin, A. Shanzer, J. Am. Chem. Soc.
2004, 126, 15400 – 15401; e) A. P. de Silva, N. D. McClenaghan,
Chem. Eur. J. 2004, 10, 574 – 586; f) A. Coskun, E. Deniz, E. U.
Akkaya, Org. Lett. 2005, 7, 5187 – 5189; g) D. Margulies, G.
Melman, A. Shanzer, Nat. Mater. 2005, 4, 768 – 771; h) J.
Andreasson, S. D. Straight, G. Kodis, C. D. Park, M. Ham-
bourger, M. Gervaldo, B. Albinsson, T. A. Moore, A. L. Moore,
D. Gust, J. Am. Chem. Soc. 2006, 128, 16259 – 16265; i) U.
Pischel, Angew. Chem. 2007, 119, 4100 – 4115; Angew. Chem. Int.
Ed. 2007, 46, 4026 – 4040; j) S. Z. Kou, H. N. Lee, D. Van Noort,
K. M. K. Swamy, S. H. Kim, J. H. Soh, K. M. Lee, S. W. Nam, J.
Yoon, S. Park, Angew. Chem. 2008, 120, 886 – 890; Angew. Chem.
Int. Ed. 2008, 47, 872 – 876; k) L. Zhang, W. A. Whitfield, L. Zhu,
Chem. Commun. 2008, 1880 – 1882; l) N. Wagner, G. Ashkenasy,
Chem. Eur. J. 2009, 15, 1765 – 1775; m) S. Kumar, V. Luxami, R.
Saini, D. Kaur, Chem. Commun. 2009, 3044 – 3046; n) O. A.
Bozdemir, R. Guliyev, O. Buyukcakir, S. Selcuk, S. Kolemen, G.
Gulseren, T. Nalbantoglu, H. Boyaci, E. U. Akkaya, J. Am.
Chem. Soc. 2010, 132, 8029 – 8036; o) D.-H. Qu, Q. C. Wang, H.
Tian, Angew. Chem. 2005, 117, 5430 – 5433; Angew. Chem. Int.
Ed. 2005, 44, 5296 – 5299.
Table 1: Photophysical parameters for the EET integration scheme.
Compound
lmax
D[c] A[c]
emax
F[a]
t [ns][b]
D
A
D
A
t1
t2
2
562
562
611
573
680
642
84000
84000
51000
51000
52000
58000
0.1
0.71
0.13
0.56
0.036
0.24
3.91
3.95
3.15
–
2.01
–
2+ZnII
6
6+HgII
7
7+HgII
8
563 682 125300 68000 0.002 0.004 0.32 3.63
567 681 125300 67300 0.024 0.015 0.71 3.58
8+ZnII
8+ZnII +HgII 567 642 137600 71000 0.036 0.190 0.82 3.70
[a] Quantum yields for all compounds were determined in reference to
Sulforhodamine 101 (F=0.90 in ethanol). [b] Emission lifetimes (t),
unless two numbers are listed, correspond to single-exponential decays.
Compound 2 was excited at 567 nm, 6 at 610 nm, 7 at 680 nm, and 8 at
575 nm. [c] D stands for the energy donor moiety, and A stands for the
acceptor moiety. Data under these columns are related to these
molecular units.
evaluation. Binding constants of the ligand–metal ion pairs
support this argument and were reported.[4n] The absorbance
spectra obtained for the integrated logic compound 8 under
various conditions (Figure 3) shows this result unequivocally.
ZnII ions do not bind to the azathiacrown ligand.
In conclusion, energy transfer (EET) and modulation of
the inner filter effect (IFE) offer two possible methodologies
for concatenation of two logic gates. The EET approach is
particularly appealing because it involves physical connection
of two logic gates through a chemical reaction. There are still
issues to be addressed, such as the maximum number of gates
that can be integrated based on an EET approach, but even
the slightest improvements in mimicking silicon circuitry may
yield huge leaps of advance owing to the molecular nature of
these particular designs.[3k] While other approaches, including
self-assembling components, are possible, we are confident
that clickable molecular logic gates are highly promising.
Demonstration of more complex examples of physically
integrated logic gates is to be expected. Our work along
those lines is in progress.
[5] J. Andreasson, S. D. Straight, S. Bandyopadhyay, R. H. Mitchell,
T. A. Moore, A. L. Moore, D. Gust, Angew. Chem. 2007, 119,
976 – 979; Angew. Chem. Int. Ed. 2007, 46, 958 – 961; b) M.
Amelia, M. Baroccini, A. Credi, Angew. Chem. 2008, 120, 6336 –
6339; Angew. Chem. Int. Ed. 2008, 47, 6240 – 6243.
[6] a) Z. Guo, W. Zhu, L. Shen, H. Tian, Angew. Chem. 2007, 119,
5645 – 5649; Angew. Chem. Int. Ed. 2007, 46, 5549 – 5553; b) D.
Margulies, C. E. Felder, G. Melman, A. Shanzer, J. Am. Chem.
Soc. 2007, 129, 347 – 354; c) W. Sun, C. Zhou, C. Xu, C. J. Fang,
C. Zhang, Z. X. Li, C. H. Yan, Chem. Eur. J. 2008, 14, 6342 –
6351; d) M. Suresh, A. Gosh, A. Das, Chem. Commun. 2008,
3906; e) J. Andreasson, S. D. Straight, T. A. Moore, A. L. Moore,
D. Gust, Chem. Eur. J. 2009, 15, 3936 – 3939; f) M. Kumar, A.
Dhir, V. Bhalla, Org. Lett. 2009, 11, 2567 – 2570.
Received: June 19, 2011
Published online: August 25, 2011
[7] a) J. Andreasson, S. D. Straight, T. A. Moore, A. L. Moore, D.
Gust, J. Am. Chem. Soc. 2008, 130, 11122 – 11128; b) H. Tian,
Angew. Chem. 2010, 122, 4818 – 4820; Angew. Chem. Int. Ed.
2010, 49, 4710 – 4712.
[8] a) G. De Ruiter, E. Tartakovsky, N. Oded, M. E. van der Boom,
Angew. Chem. 2010, 122, 173 – 176; Angew. Chem. Int. Ed. 2010,
49, 169 – 172; b) U. Pischel, J. Andreasson, New J. Chem. 2010,
34, 2701 – 2703; c) U. Pischel, Angew. Chem. 2010, 122, 1396 –
1398; Angew. Chem. Int. Ed. 2010, 49, 1356 – 1358; d) G.
de Ruiter, L. Motiei, J. Choudhury, N. Oded, M. E. van der
Boom, Angew. Chem. 2010, 122, 4890 – 4893; Angew. Chem. Int.
Ed. 2010, 49, 4780 – 4783.
[9] a) R. Baron, O. Lioubashevski, E. Katz, T. Niazov, I. Willner,
Angew. Chem. 2006, 118, 1602 – 1606; Angew. Chem. Int. Ed.
2006, 45, 1572 – 1576; b) T. Niazov, R. Baron, E. Katz, O.
Lioubashevski, I. Willner, Proc. Natl. Acad. Sci. USA 2006, 103,
17160 – 17163; c) G. Strack, M. Ornatska, M. Pita, E. Katz,
Keywords: concatenation · energy transfer · fluorescence ·
logic gates · sensors
.
[1] V. V. Zhirnov, R. K. Cavin, J. A. Hutchby, G. I. Bourianoff, Proc.
IEEE 2003, 91, 1934 – 1939.
[2] A. P. de Silva, H. Q. N. Gunaratne, C. P. McCoy, Nature 1993,
364, 42 – 44.
[3] a) A. Credi, V. Balzani, S. J. Langford, J. F. Stoddart, J. Am.
Chem. Soc. 1997, 119, 2679 – 2681; b) H. T. Baytekin, E. U.
Akkaya, Org. Lett. 2000, 2, 1725 – 1727; c) A. P. de Silva, N. D.
McClenaghan, Chem. Eur. J. 2002, 8, 4935 – 4945; d) A. P.
de Silva, M. R. James, B. O. F. McKinney, P. A. Pears, S. M.
Weir, Nat. Mater. 2006, 5, 787 – 790; e) A. P. de Silva, S. S. K.
de Silva, N. C. W. Goonesekera, H. Q. N Gunaratne, P. L. M.
9830 www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 9826 –9831

J. Am. Chem. Soc. 2008, 130, 4234 – 4235; d) M. Privman, T. K.
Tam, M. Pita, E. Katz, J. Am. Chem. Soc. 2009, 131, 1314 – 1321.
[10] a) T. Gupta, M. E. van der Boom, Angew. Chem. 2008, 120,
2292 – 2294; Angew. Chem. Int. Ed. 2008, 47, 2260 – 2262; b) T.
Gupta, M. E. van der Boom, Angew. Chem. 2008, 120, 5402 –
5406; Angew. Chem. Int. Ed. 2008, 47, 5322 – 5325; c) S. Silvi,
E. C. Constable, C. E. Housecroft, J. E. Beves, E. L. Dunphy, M.
Tomasulo, F. M. Raymo, A. Credi, Chem. Eur. J. 2009, 15, 178 –
185.
[11] F. M. Raymo, S. Giordani, Proc. Natl. Acad. Sci. USA 2002, 99,
4941 – 4944.
[12] F. Remacle, S. Speiser, R. D. Levine, J. Phys. Chem. B 2001, 105,
5589 – 5591.
Angew. Chem. Int. Ed. 2011, 50, 9826 –9831
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
9831