Molecular logic gate

A molecular logic gate is a molecule that performs a logical operation based on one or more physical or chemical inputs and a single output. The field has advanced from simple logic systems based on a single chemical or physical input to molecules capable of combinatorial and sequential operations such as arithmetic operations (i. e. moleculators and memory storage algorithms). Molecular logic gates work with input signals based on chemical processes and with output signals based on spectroscopic phenomena. Logic gates are the fundamental building blocks of electrical circuits. They can be used to construct digital architectures with varying degrees of complexity by a cascade of a few to several million logic gates. Logic gates are essentially physical devices that produce a singular binary output after performing logical operations based on Boolean functions on one or more binary inputs. The concept of molecular logic gates, extending the applicability of logic gates to molecules, aims to convert chemical systems into computational units. Over the past three decades, the field has evolved to realize several practical applications in molecular electronics, biosensing, DNA computing, nanorobotics, and cell imaging, among others.

For logic gates with a single input, there are four possible output patterns. When the input is 0, the output can be either a 0 or 1. When the input is 1, the output can again be 0 or 1. The four output bit patterns that can arise corresponds to a specific logic type: PASS 0, YES, NOT, and PASS 1. PASS 0 always outputs 0, whatever the input. PASS 1 always outputs 1, whatever the input. YES outputs a 1 when the input is 1, and NOT is the inverse of YES – it outputs a 0 when the input is 1. AND, OR, XOR, NAND, NOR, XNOR, and INH are two input logic gates. The AND, OR, and XOR gates are fundamental logic gates, and the NAND, NOR, and XNOR gates are complementary to AND, OR, and XOR gates, respectively. An INHIBIT (INH) gate is a special conditional logic gate that includes a prohibitory input. When the prohibitory input is absent, the output produced depends solely on the other input.

One of the earliest ideas for the use of π conjugated molecules in molecular computation was proposed by Ari Aviram from IBM in 1988. The motivation for this work was to develop theoretical models for mixed valence type σ π σ bonded molecules and explore their stereochemical properties for potential applications in molecular devices. The system comprised two π conjugated systems, 1 and 2, made of oligothiophenes joined by a spiro linkage, and connected to gold electrodes by thiol linkers. π system 1 is non conducting in its neutral state, whereas system 2 is electrically conducting in its radical cation form. The twisted structure of the system courtesy of the spiro linkage provides hindrance to the transport of electrons between the two π systems. However, through electrodes directed toward the linkage, a strong electric field could facilitate electron transfer from system 1 to system 2, with the radical cation going the opposite way. [[File:Figure 2. Schematic of a proposed molecular electronic switch by Aviram. png|center|thumb|564x564px|Schematic of a proposed molecular electronic switch by Aviram. While a YES molecular logic gate, as described previously, can convert signals from their ionic to photonic forms (hence the term “photoionic”), they are singular input singular output systems. To build more complex molecular logic architectures, two input gates, namely AND and OR gates, are needed. Some early works made some progress in this direction, but could not realize a complete truth table as their ionic forms (protonated) could not bind to the substrate in all cases. De Silva and co. constructed an anthracene based AND gate made up of tertiary amine and benzo 18 crown 6 units, both of which were known to show photoinduced electron transfer (PET) processes. In the system shown, they both acted as receptors, connected to the anthracene based fluorophore by alkyl spacers. The PET is quenched upon coordination with protons and sodium ions, respectively, for the two receptors, and would lead the anthracene unit to fluoresce. The truth table for an AND gate was completely realized as the system would exhibit a fluorescence output only in the presence of both protons and sodium ions in the system. center|thumb|449x449px|A molecular AND gate.

An example of a YES logic gate comprises a benzo crown ether connected to a cyano substituted anthracene unit. An output of 1 (fluorescence) is obtained only when sodium ions are present in the solution (indicating an input of 1). Sodium ions are encapsulated by the crown ether, resulting in a quenching of the PET process, and causing the anthracene unit to fluoresce. center|thumb|275x275px|A YES molecular logic gate.

This molecular logic gate illustrated demonstrates the advancement from redox fluorescent switches to multi input logic gates with an electrochemical switch. This two input AND logic gate incorporates a tertiary amine proton receptor and a tetrathiafulvalene redox donor. These groups, when attached to anthracene, can simultaneously process information concerning acid concentration and oxidizing ability of the solution. center|thumb|258x258px|A two input AND molecular logic gate sensor for protons and electrons.

De Silva et al. constructed an OR molecular logic gate using an aza crown ether receptor and sodium and potassium ions as the inputs. Either of the two ions could bind to the crown ether, causing the PET to be quenched and the fluorescence to be turned on. Since either of the two ions (input “1”) could turn on the fluorescence (output “1”), the system resembled an OR logic gate. center|thumb|328x328px|A two input molecular INH logic gate.

Parker and Williams constructed a NAND logic gate based on turning on strong emission from a terbium complex of phenanthridine. When acid and oxygen (the two inputs) are absent (input “0”), the fluorescence from the terbium center is turned on (output “1”). Hence, the system acts as a molecular NAND gate. center|thumb|305x305px|A two input molecular NAND logic gate.

Akkaya and coworkers demonstrated a molecular NOR gate using a boradiazaindacene system. Fluorescence of the highly emissive boradiazaindacene (input “1”) was found to be quenched in the presence of either a zinc salt [Zn(II)] or trifluoroacetic acid (TFA). The system, thus, could realize the truth table of a NOR logic gate. center|thumb|315x315px|A two input molecular NOR logic gate.

In compound B in Figure 10 B, the bottom section contains a tertiary amino group, also capable of binding to protons. In this system, fluorescence only takes place when both cations available. The presence of both cations hinders photoinduced electron transfer (PET) allowing compound B to fluoresce. In the absence of both or either ion, fluorescence is quenched by PET, which involves an electron transfer from either the nitrogen atom or the oxygen atoms, or both to the anthracenyl group. When both receptors are bound to calcium ions and protons respectively, both PET channels are shut off. The overall result of Compound B is AND logic, since an output of "1" (fluorescence) occurs only when both Ca2+ and H+ are present in solution, that is, have values as "1". With both systems run in parallel and with monitoring of transmittance for system A and fluorescence for system B the result is a half adder capable of reproducing the equation 1 + 1 = 2.
center|thumb|493x493px|A triple input half adder system based on AND gates.

Fluoride (F ) and acetate (CH3COO ) anions are among the most important ones in the context of human health and well being. The former, though used extensively in health care, is known for its toxicity and corrosiveness. The latter can cause alkalosis and affect metabolic pathways beyond a certain concentration. Hence, it is crucial to develop methods to detect these anions in aqueous media. Bhat et al. constructed an INHIBIT gate with receptors that bind selectively to F‑ and CH3COO anions. The system used changes in absorbance as a colorimetric based output to detect the concentration of anions. Wen and coworkers also designed an INHIBIT molecular logic gate with Fe3+ and EDTA as the inputs and a fluorescence output for the detection of ferric ions in solutions. The fluorescence of the system is quenched if and only if Fe3+ input is present and EDTA is absent. Heavy metal ions provide a persistent threat to human health because of their inherent toxicity and low degradability. Several molecular logic gate based systems have been constructed to detect ions such as Cd2+, Hg2+/Pb2+, and Ag+. In their work, Chen and coworkers demonstrated that logic gate based systems could be used to detect Cd2+ ions in rice samples, thereby widening the scope of the field to safety detection in food materials, too. Hence, it is imperative to detect the presence of cancerous cells early. An important biomarker, microRNA (miRNA), is crucial in this detection via its expression patterns. Zhang et al. have demonstrated an INHIBIT OR gate cascade for the purpose, Yue and co. used an AND gate to construct a system with two miRNA inputs and a quantum dot photoluminescence output, and Peng et al. also constructed an AND gate based dual input system for the simultaneous detection of miRNAs from tumor cells. Akkaya et al. illustrated the application of a logic gate for photodynamic therapy in their work. A bodipy dye attached to a crown ether and two pyridyl groups separated by spacers works according to an AND logic gate. The molecule works as a photodynamic agent upon irradiation at 660 nm under conditions of relatively high sodium and proton ion concentrations by converting triplet oxygen to cytotoxic singlet oxygen. This prototypical example would take advantage of the higher sodium levels and lower pH in tumor tissue compared to the levels in normal cells. When these two cancer related cellular parameters are satisfied, a change is observed in the absorbance spectrum. This technique could be useful for the treatment of malignant tumors as it is non invasive and specific. center|thumb|353x353px|Two input AND logic gate with photodynamic therapeutic applications.

The concept of DNA computing came about as a way to address storage density issues because of the exploding volumes of data information. Theoretically, a gram of single stranded DNA is capable of storing over 400 exabytes (order of 1020 bytes) of data at a density of two bits per nucleotide. Leonard Adleman is credited with having established the field in 1994. Recently, molecular logic gate systems have been utilized in DNA computing models. Massey and coworkers constructed photonic DNA molecular logic circuits using cascades of AND, OR, NAND, and NOR molecular logic gates. They used lanthanide complexes as fluorescent markers, and their luminescent outputs were detected by FRET based devices at the terminals of DNA strands. Works by Campbell et al. on demonstrating NOT, AND, OR, and XNOR logic systems based on DNA crossover tiles, Bader and co. on manipulating the DNA G quadruplex structure to realize YES, AND, and OR logic operations, and Chatterjee and coworkers on constructing logic gates using reactive DNA hairpins on DNA origami surfaces are some examples that mark the progress in the field of logic gate based DNA computing.

Nanorobots have the potential to transform drug delivery processes and biological computing. Llopis Lorente and co. developed a nanorobot that can perform logic operations and process information on glucose and urea. Thubagere and coworkers designed a DNA molecular nanorobot capable of sorting chemical cargo. The system could work without additional power as the robot was capable of walking across the DNA origami surface on its two feet. It also had an arm to transport cargo. Molecular sequential logic is exemplified by Margulies et al., where they demonstrate a molecular keypad lock resembling the processing capabilities of an electronic security device which is equivalent to incorporates several interconnected AND logic gates in parallel. The molecule mimics an electronic keypad of an automated teller machine (ATM). The output signals are dependent not only on the combination of inputs but also on the correct order of inputs; i. e. the correct password must be entered. The molecule was designed using pyrene and fluorescein fluorophores connected by a siderophore, which binds to Fe(III), and the acidic of the solution changes the fluorescence properties of the fluorescein fluorophore. Molecular logic gate systems can theoretically overcome the problems arising when semiconductors approach nano dimensions. Molecular logic gates are more versatile than their silicon counterparts, with phenomena such as superposed logic unavailable to semiconductor electronics.