Chemical input multiplicity facilitates arithmetical processing

Article abstract of DOI:10.1021/ja0453329

We describe the design and function of a molecular logic system, by which a combinatorial recognition of the input signals is utilized to efficiently process chemically encoded information. Each chemical input can target simultaneously multiple domains on

Full text of DOI:10.1021/ja0453329

Published on Web 11/05/2004
Chemical Input Multiplicity Facilitates Arithmetical Processing
David Margulies, Galina Melman, Clifford E. Felder, Rina Arad-Yellin, and Abraham Shanzer*
Department of Organic Chemistry, The Weizmann Institute of Science, RehoVot 76100, Israel
Received August 3, 2004; E-mail: abraham.shanzer@weizmann.ac.il
Boolean functions at the molecular scale have been possible for
some time through a variety of approaches1 that harness the abilities
of molecules to process information. In particular, molecular logic
gates2 such as AND,2a XOR,2b and INHIBIT2c that produce light
signals in response to a variety of chemical inputs have been studied
extensively. The vitality of this approach was recently highlighted
when basic arithmetic functions involving two, one-digit binary
numbers (bits), such as addition3 or subtraction,4 were performed
by molecules. A suggestion for more complex addition function
by multiphoton spectroscopy has also been reported.5 The realization
that several logic functions can be integrated within a single
molecule has led to the design of molecular systems whose logic
functions can be reconfigured either by generating multiple light
signals6 or by altering their chemical inputs.7 It is likely that by
combining these approaches, molecular logic gates with superior
Figure 1. Truth table of half-adder and half-subtractor logic circuits and
processing capabilities will emerge.
the distinct fluorescent states of molecule 1, endowed with similar processing
We propose a strategy based on input signal multiplicity, in which
each chemical input can be recognized simultaneously at several
domains within the same molecule, forming ideally distinct chemical
states, each with its characteristic signaling properties. This approach
resembles somewhat the way that our olfactory system works, where
a specific odorant molecule, consisting of different functional
groups, selectively target several receptors simultaneously.8 At the
molecular level, a single molecular platform integrating multiple
recognition sites for each input is expected to respond in parallel
to a variety of reagents and thereby provide a range of Boolean
functions.
We describe a first step toward this goal by demonstrating a
reconfigurable molecular logic system, exhibiting parallelism in both
its chemical inputs and light outputs, which by simple alternation
of the input signals can perform distinct algebraic operations
between two bits, solely in the fluorescence mode. The molecular
arithmetic system is simple to operate, as it requires a single type
of processing molecule, excited at the same wavelength of light,
and uses a single measuring setup for straightforward “reading” of
the arithmetic results.
Three logic gates, AND, Exclusive OR (XOR) and INHIBIT,
operating in parallel, can perform simple arithmetic operations
involving two bits. A half-adder3,5 can carry out elementary addition
utilizing the XOR gate to generate the sum digit (S) and the AND
gate to produce the carry (C). A half-subtractor4 is generated through
XOR and INHIBIT logic devices, which produce the difference
(D) and the borrow (B), bits, respectively. The truth table for these
operations is shown in Figure 1a.
Molecule 1 (Figure 1b) possesses similar numerical processing
abilities. Our design is based on a modified bacterial iron carrier9
(siderophore) to which two fluorophores, pyrene (donor) and
protonable fluorescein (acceptor), whose emission spectra do not
overlap, are attached at its termini. Upon excitation of the pyrene
(344 nm) the molecule can switch between three distinct fluorescent
states with emission of blue, green, or off luminescence (Figure
1c). In basic pH the fluorescein is present mainly in its mono or
abilities. (a) Outputs are carry (C), sum (S), borrow (B), and difference
(D). (b) Molecule 1 is composed of a siderophoric receptor, pyrene (Pyr),
and protonable fluorescein (Flu). (c) Left: photograph of 0.1 mM ligand 1
in ethanol, excited with UV light, upon addition of 0.1 N aqueous sodium
acetate, 0.1 N acetic acid and 1 equiv of iron(III) ions. Right: Schematic
presentation describing the three fluorescent states shown in the photograph.
dianion fluorescent form,10 and therefore fluorescence resonance
energy transfer (FRET) takes place between the donor and acceptor,
leading to an intense green emission of the fluorescein. Turning
the solution acidic causes protonation of the fluorescein to its
inactive form, and the green fluorescein emission is replaced by a
brilliant blue pyrene luminescence. Addition of iron(III) results in
efficient fluorescent quenching9,11 by the bound metal ion.
However, the quenching efficiency of the fluorescein emission
was found to be dependent on its protonation state. While the
emission of the monoanionic fluorescein in ethanol10b was fully
quenched, at higher pH, when it was further deprotonated, an
emission was detected even from the iron-bound fluorescein.
Accordingly, the complex, 1-Fe(III), can be viewed as a molecular
scaffold with four exchangeable domains, COH, COO-, CONO-,
and Fe(III), that can be targeted either singly or in combinations
with mono- or multifunctional chemical inputs to yield Boolean
patterns of various fluorescence outputs (Figure 2).
The performance of the iron complex as a half-subtractor, acting
simultaneously as XOR and INHIBIT logic gates, can be demon-
strated by monitoring the blue and the green emissions obtained
with acid and base as input signals (Figure 2A). In ethanol solution,
the complex emission is inherently quenched. However, when acid
(HCl) is added, the pH of the system decreases, leading to
simultaneous protonation of the fluorescein and the hydroxamate
units, followed by the release of the bound metal ion, as expected
from siderophore-iron(III) complexes in low pH.12 Since the
fluorescence of the pyrene is not quenched and the fluorescein is
in its inactive form, emission is observed solely at 390 nm.
Alternatively, addition of base (sodium acetate) to the ferric complex
results in a green emission at 525 nm, due to ionization of the
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C O M M U N I C A T I O N S
removed, an intense green emission of the fluorescein at 525 nm
is detected. Consequently, by monitoring the emission signals at
525 nm, an AND logic gate is obtained, while detection at 390 nm
results in an INHIBIT logic gate. The truth table in Figure 2
summarizes the conditions by which the operation of this AND
gate in parallel to the previously described XOR logic gate offer
an input-configurable half-adder which in turn can produce sum
(S) and carry (C) bits of 0+0, 1+0, 0+1, and 1+1.
Molecular logic systems operating via combinatorial recognition
of input molecules provide a unique signaling pattern for each
reagent and therefore could handle considerable amounts of
chemically encoded information.8 The concept described in this
report is of a general nature and can be applied to extend the
processing abilities of any molecular logic gate hosting a substrate
to which a competitor is known by readjusting its signaling moieties
to respond to the inhibitor or to some of its physicochemical
properties.
Acknowledgment. We thank Mrs. Rachel Lazar, Mrs. Sara
Rubinraut, and Dr. Brenda Mester for their skillful assistance.
Support from the European Union (HPRN-CT-2000-00029) and
the Helen and Martin Kimmel Center for Molecular Design are
greatly acknowledged.
Figure 2. (Top) Schematic presentation describing the combinatorial effects
of the chemical inputs on the iron complex and the resulting fluorescence
emissions for (A) XOR/INHIBIT and (B) AND/INHIBIT logic patterns,
together operating as a half-adder and a half-subtractor, solely in the
fluorescence mode. (Bottom) Truth table for 1.5 µM 1-Fe(III) in EtOH
(1.5 mL) excited at 344 nm. Inputs: 20 µL aqueous solution of (a) 2 M
AcONa, (b) 1 M HCl, (c) saturated EDTA. Outputs: (d) fluorescence
outputs, intensity in arbitrary units. (C) carry, (B) borrow, (S/D) sum/
difference
Supporting Information Available: The synthesis of 1, additional
spectral data, and a representation of half-adder and half subtractor
electronic logic circuits. This material is available free of charge via
the Internet at http://pubs.acs.org.
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(III) ions, resulting in exclusive emission from the pyrene at 390
nm. Addition of a base (sodium acetate) causes ionization of the
fluorescein, but without removal of the iron, so that a faint green
emission is observed below the threshold barrier. Only when both
inputs are present, namely, the solution is basic and the iron is
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