2:1 Multiplexing Function in a Simple Molecular System

1-[(Anthracen-9-yl)methylene] thiosemicarbazide shows weak fluorescence due to a photo-induced electron transfer (PET) process from the thiosemicarbazide moiety to the excited anthracene. The anthracene emission can be recovered via protonation of the amine as the protonated aminomethylene as an electron-withdrawing group that suppresses the PET process. Similarly, chelation between the ligand and the metal ions can also suppress the PET process and results in a fluorescence enhancement (CHEF). When solvents are introduced as the third control, a molecular 2:1 multiplexer is constructed to report selectively the inputs. Therefore, a molecular 2:1 multiplexer is realized in a simple molecular system.


Introduction
There is increasing interesting in exploring single molecule species that could be potentially applied in the construction of binary logic devices and future computers at the molecular scale [1][2][3][4][5][6][7][8]. Since the OPEN ACCESS first molecular AND gate was reported [9], all common essential logic gates including AND, NOT, OR, YES, INHIBIT, XOR, NAND and NOR, which are used in conventional silicon circuitry, have been mimicked at the molecular level with chemical or optical signals [10][11][12][13][14][15][16][17][18][19][20][21]. With all these logic gates in hand, the next step is to construct molecular logic networks taking advantage of functional integration within a single molecule via rational chemical design. This is prior to relying on extensive physical connection of elementary gates. Recently, molecular-scale arithmetic has also been reported [21][22][23][24][25][26][27][28][29][30]. Those single molecule-based combinatorial circuits are more important because they are fundamental to a complex information processing system. Tian reported a fluorophore capable of logic memory [31]. We have systematically explored the combination of logic functions and realized a safe computing platform with user-identity-directed arithmetic functions to defend information risk [32,33]. An important function in information technology, e.g. signal multiplexing, has been realized based on the molecules [34][35][36]. The construction of molecule-based 1:2 digital demultiplexer was also reported [37,38]. The signal multiplexing/demultiplexing was demonstrated in 8-methoxyquinoline and enzymes [39,40]. In spite of various logic functions mimicked at molecular level, however, the combination and integration of advanced functions is still in the infant stage and reports on this subject are rare [41][42][43][44][45].
In our previous work, up to seven binary logic gates were realized within a single molecule, in which redox-active tetrathiafulvalene (TTF) was utilized as a switch to control the fluorescence [46]. Herein, we report a molecular system which is capable of performing multiplexing function in response to chemical stimuli.
In the present work, the fluorescence of anthracene in the simple molecule 1-[(anthracen-9-yl) methylene] thiosemicarbazide (L, Figure 1) [47,48] is tuned to realize a molecular 2:1 multiplexer with anthracene as a signal unit via tuning the PET process. Protonation of amine and chelation with metal ions can suppress the photo-induced electron transfer (PET) process. Combined with the solvents as control inputs to switch the fluorescent output, the ligand L can report the binary state of either one of these inputs or the other.

Experimental Section
The UV-vis absorption spectra were recorded on a Shimadzu 2500 UV-VIS spectrophotometer. The fluorescence spectra were recorded on a Shimadzu RF-5301 spectrofluorophotometer using 5 nm input and 5 nm output width. 1 H-and 13 C-NMR (TMS) are recorded on a Bruker Avance II 500MHz spectrometer. The mass spectra were measured on a Waters Quattro micro TM API mass spectrometer. Elemental analyses were performed on a Vario EI Elementar system.

Synthesis of the Ligand L
When anthracene-10-carbaldehyde was treated with thiosemicarbazide in methanol, the ligand L was readily formed as an orange microcrystalline solid appearing in the reaction medium, and it was characterized with elemental analysis (EA), IR, MS, and NMR spectra data. 1

Photophysical Properties of the Ligand L
The photophysical properties of the ligand L were initially examined in tetrahydrofuran (THF) and methanol. As shown in Figure 2, characteristic anthracene absorption bands appear in the range of 335-500 nm in UV-Vis spectra [47]. The fluorescence spectrum of the ligand in THF solution displays peaks at 412, 437 and 470 nm ( Figure 3). The emission intensity of the ligand L is significantly reduced through a photo-induced electron transfer (PET) process, with the electron-transfer from the electron-donor thiosemicarbazide moiety to the excited anthracene. When the amine group is proton-free, it could serve as a PET donor (ΔG PET = −0.1 eV) [49][50][51]. If protons are present in sufficient concentration, the protonated aminomethylene behaves as an electron-withdrawing group which disturbs and suppresses the PET process from the thiosemicarbazide moiety, thus producing an enhancement of the fluorescent emission. In addition, chelation enhanced fluorescence (CHEF) is popular for chemosenors base on PET mechanism to sensing metal ions [52]. Two above points have been useful to design chemosensors based on the PET mechanism.  and LUMO (lowest unoccupied molecular orbit) distribution of the L were determined by density functional theory (DFT) calculations. As shown in Figure 5, the HOMO distribution is mainly located diffusely over the thiourea group, thus the S and N atoms are electron-rich centers and exhibit high affinity for the metal ion, which contributes to CHEF effect. In methanol solution, however, the fluorescence is quenched. This might be due to the intrinsic fluorescence quenching by mechanisms inherent to paramagnetic species Cu 2+ in high dielectric and polar methanol. The communication between paramagnetic Cu 2+ and fluorophore is predominant, and thus the fluorescence is quenched.

Binary Logic Analysis for Molecular Logic Circuit
Fluorescence is one of the most widely employed signals owing to its high sensitivity, feasibility in detection, and low cost in operation. Since systems containing fluorophores can be switched between emissive state and quenched state via manipulation of the PET process, the chemical system described above could be a simple functional model of logic gate with tuning the fluorescence as output signal.
It is interesting to note that the logic analysis of the present system is complex if the solvent is considered as the control input. In this context, the logic system described here is a chemical model of a 2:1 multiplexer. Physically, a multiplexer is a communication device that combines multiple inputs into an aggregate signal to be transported via a single transmission channel. Simply, it is a data selector which outputs any one of several possible inputs via a control switch.
In the present case, the solvent as the third input acts like a mechanical rotary switch to control the logic functions of the molecule, enabling the molecule to output selectively the desirable data from all the inputs. With the input of the proton and the metal ion Cu 2+ while solvent as the control, changes of the fluorescent emission of the ligand corresponding to two different inputs mimic the digital selection

Conclusions
In summary, we have demonstrated a combinational logic circuit of molecular multiplexer within a simple molecular system, where the emission of anthracene and the solvent effect are employed as signaling and switch control, respectively. The work presented herein opens the possibility for further development of chemical logic systems, and thus for the construction of molecular digital devices which are likely to be evolved into components of future molecular computers such as a wet computer. Further investigation of this topic is underway in our lab.