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Dual macro-cyclic component based logic diversity
Journal Pre-proof Dual macro-cyclic component based logic diversity Monaj Karar, Provakar Paul, Suvendu Paul, Basudeb Haldar, Arabinda Mallick, Tapas Majumdar PII:
S0143-7208(19)32038-8
DOI:
https://doi.org/10.1016/j.dyepig.2019.108060
Reference:
DYPI 108060
To appear in:
Dyes and Pigments
Received Date: 29 August 2019 Revised Date:
11 November 2019
Accepted Date: 18 November 2019
Please cite this article as: Karar M, Paul P, Paul S, Haldar B, Mallick A, Majumdar T, Dual macrocyclic component based logic diversity, Dyes and Pigments (2019), doi: https://doi.org/10.1016/ j.dyepig.2019.108060. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.
Dual Macro-cyclic Component Based Logic Diversity Monaj Karara, Provakar Paula, Suvendu Paula, Basudeb Haldarc, Arabinda Mallick*b, Tapas Majumdar*a a
Department of Chemistry, University of Kalyani, Nadia, West Bengal, 741235, India
b
Department of Chemistry, Kazi Nazrul University, Asansol, West Bengal, 713340, India
c
Department of Chemistry, Vivekananda Mahavidyalaya, Burdwan, West Bengal, 713103, India
E-mail AM: [email protected]; TM: [email protected]
Abstract In continuation of our recent studies on the photophysics of a photodynamic therapeutic agent, harmine (HM) in model membrane, the present contribution highlights a new model to design multiple logic circuits, a memory device and a molecular lock regulated by dual macrocyclic components as chemical inputs. The unique reversible photoswitching regulated by macrocyclic components plays decisive role in the manifestation of the final outputs for the logic functions. Inspired by this phenomenon, herein, we are reporting the use of a photosensitizer molecule for designing of various logic circuits at molecular level with the intention to escalate the next generation molecular logic arena. For these desired outsets, fluorescence spectroscopic changes of HM upon addition of macrocyclic components (CTAB and β-CD) were utilized. Beyond the simple single input single output logic gates (NOT, YES, PASS 0 and PASS 1), we were also able to design IMPLICATION and INHIBIT gates. In addition to different logic functions, the modulations of the optical responses of HM driven by the macrocyclic components were employed to design “EraseRead-Write-Read” and “Write-Read-Erase-Read” type memory units. Moreover, considering the optical responses of HM we proposed a supramolecular keypad lock operated through unique sequential entry of opto-chemical passwords.
Keywords: Harmine, Keypad lock, Macrocyclics, Memory unit, Molecular logic gate. 1. Introduction Depending on the pH of the aqueous medium, most of the photosensitizer molecules might exist in four different prototropic forms (neutral, cation, anionic and zwitterion) in the electronic ground and excited states [1]. Use of photosensitizer molecules for the treatment of neoplastic diseases, generally known as photodynamic therapy (PDT), has become a topic of growing medical interest. PDT produces singlet oxygen that damages the cancer cells. This is a standard method for cancer treatment [2,3]. Over the last few decades, extensive preclinical and clinical research established HM (Scheme
1) as a potential anticancer agent [2-6]. In addition, HM exhibits strong medicinal activities towards tumour proliferation and inducing apoptosis [3]. Efficacy of the phototherapeutic action mainly depends on the bio-distribution of the probe molecule in the cytoplasmic and mitochondrial membranes, its retention and the nature of binding inside the target cells. Studies in living cells revealed that molecules belonging to this class exist both in neutral and protonated forms in the cytoplasm, whereas only in its protonated form inside the nucleus. As a matter of fact, the functions of these biologically active molecules are very much correlated with their structural forms [1,7]. Recently, studies on HM by Varela et al.[7] revealed that the neutral form of HM shows significant triplet state yield and this long-lived triplet state might play important role in their in vivo photosensitization reactions in presence of oxygen. This phenomenon could be accounted for strong anti-cancer activities of the neutral form of HM. Under this situation, it is very much logical to assume that, there must be some in-situ molecular mechanism to promote a particular prototropic form of probes like HM to achieve better biological efficacy in a specific environment. Logic gates evolved with a variety of applications that transformed the world through digitization. In many such logic gates, two binary inputs are converted to a single binary output and might be extended to develop a third logic gate by accepting the outputs as inputs. de Silva et al.[8] first proposed the idea of photonic logic device on the molecular platform. Till date, excellent researches came up with the development of molecular systems executing binary logic operations paving the path for the construction of simple and complex electronic or photonic driven systems and networks that function as molecular-level devices [9,10]. Besides, the uses of these logic operations based on simple host-guest complexation were well advanced for the sensing studies, drug delivery, theranostics, and materials chemistry [11-17]. Present molecular logic arena is based on designing of multiple logic gates on the unimolecular platform [18-24] in order to achieve functional complexity of integrated circuits beyond basic logic gates. There are many reports where multiple logic gates were designed on a unimolecular platform based on ions or/and molecules as chemical inputs [18-27]. Since the early report by de Silva et al.[28] to employ macrocyclic compound as molecular logic input, limited number of reports are available where macrocyclic components could replace the usual chemical inputs to construct molecular logic devices [29]. In continuation of our earlier report [30] on HM, we planned to execute the unimolecular platform of HM for the designing of multiple logic gates employing the macrocyclic components as chemical inputs. Among many possibilities, different sets of input-output combinations were compiled to mimic the basic binary operations of multiple and fully different logic gates. Now, it will be extremely helpful to predict the exact prototropic form of HM present inside the cell, based on the specific logic function generated for a particular set of inputs. We could assume that the molecules like HM and other members of β-carboline family containing acidic pyrrolic hydrogen as well as a basic pyridinic nitrogen (Scheme 1) supposed to display similar kind of optical responses upon interactions with these macrocyclic components like micelles and β-cyclodextrin (β-CD). Therefore,
this report represents a general route for the designing of multiple logic gates of a class of molecules upon sequential interaction with these macrocyclics. In recent times, scientists have been devoting enormous efforts to design molecular keypad locks based on the chemicals as well as optical parameters as inputs. In this regard the development of a supramolecular keypad lock by Pischel et al. [31] is remarkable. In this report, we designed a supramolecular keypad lock considering macrocyclic components along with excitation light as input keys that operate the lock.
Scheme 1. Molecular structure of Harmine.
2. Materials and methods HM and β-CD were procured from Aldrich (Missouri, USA) and used as received. The surfactant, CTAB was procured from Lancaster (England) and used as received. Spectroscopy grade water from Millipore was used throughout the experiment. Steady-state fluorescence experiments were carried out on Hitachi F-7000 spectrofluorometer (Tokyo, Japan). Slit ratio was kept to 1 (Ex slit = 5 nm, Em slit = 5 nm) and the PMT voltage was kept at 500V. A cuvette 10 mm width was used for fluorescence measurement. Initial concentration of HM was 0.335 mM. All the fluorescence measurements were after proper thermal equilibration of the solution in the quartz cuvette through properly stirred on a magnetic stirrer. Due to very low solubility of β-CD in water pre-weighted solid β-CD were added in the cuvette and stirred for the sufficient time to achieve a homogeneous thermally equilibrated solution. Temperature was kept constant at 300 K throughout the experiment.
3. Results and discussion 3.1 Photophysical studies Steady state fluorescence spectroscopic analysis of HM (Fig. 1) in aqueous and micellar environments was already discussed in our previous report [30]. However, for the general readership and to make the base to understand the logic diversity, we highlighted here the salient features of the steady state fluorescence results. Room temperature emission spectrum of the cationic form of HM in aqueous medium could be characterized by a slightly broad unstructured band with a maximum at around 416 nm. Gradual addition of CTAB to the aqueous solution of the probe led to the appearance of a band at 365 nm corresponding to the neutral species at the cost of that of the cationic species through a clear isoemissive point at around 400 nm. Dramatic changes of emission spectra upon addition of CTAB
indicated a structural switchover of HM through a dynamic equilibrium in the excited state. Interesting reverse switching of emission band from 365 to 416 nm was observed upon the addition of β-CD within HM-CTAB i.e., the cationic band at 416 nm was almost restored with the expense of neutral emission band at 365 nm. Summarized spectroscopic results were represented in Fig. 1.
Fig. 1. Individual fluorescence spectrum of HM and the resultant spectra of individual and sequential interactions of CTAB and β-CD with HM; temp. = 300 K
3.2 Application towards logic diversity Distinct optical responses of HM due to inter-conversion of cationic and neutral forms with sequential addition of CTAB and β-CD were compiled to mimic quite a few truth tables of corresponding logic gates. Fluorescence spectral responses of HM at 416 nm or 365 nm were considered as “output” to generate the truth tables (Table 1 and 2). For both the emission channels, a threshold value of emission intensity was set, above which the binary value was considered as “1” and below as “0” respectively. Considering HM or HM-CTAB as distinct devices and employing CTAB or β-CD as single chemical input, we were able to construct single output based “NOT”, “YES”, “PASS 0” and “PASS 1” gates at the 365 and 416 nm optical output channels. In addition, on the unimolecular platform of HM, engaging both chemical inputs we designed “IMPLICATION” and “INHIBIT” logic gates. The binary responses of the “INHIBIT” logic gate is complementary to an “IMPLICATION” gate and the function is quite similar to that of IF-THEN and NOT operations. Considering HM as device and CTAB as the single chemical input, a “NOT” logic was designed at 416 nm optical response as primary output. Now, this system will act as a “YES” logic gate if we monitor the optical output at 365 nm (Table 1a and Fig. 2a & 2b). Table 1. Construction of truth tables for NOT, YES, PASS 0 and PASS 1 logic gates based on fluorescence responses of HM with CTAB and β-CD (colours (synchronized with the Figure 1) in the rows represents the resultant states generated after the chemical input.
Similarly, if we consider HM-CTAB as the main chemical device another pair of YES and NOT logic gate could be designed. Interestingly, for HM-CTAB device optical output channels for YES and NOT logic gates were completely inverse to that of HM as device i.e., YES gate at 416 nm and NOT gate at 365 nm output channels (Table 1b and Fig. 2c & 2d).
Fig. 2. (a) NOT and (b) YES logic gate layouts considering HM as device; (c) YES and (d) NOT logic gate layouts considering HM-CTAB as device; PASS 0 (e) and PASS 1 (f) logic gate layouts based on HM as device. Another two “single input single output” logic gates i.e. “PASS 0” and “PASS 1” were designed on the unimolecular platform of HM considering β-CD as the single chemical input. The binary conversion of 365 nm and 416 nm emission channel responses exactly matched with the corresponding truth tables of the PASS 0 and PASS 1 logic gates respectively (Table 1, Fig. 2e & 2f). Table 2. Construction of truth tables based on fluorescence responses of HM upon interactions with CTAB and β-CD individually and sequentially.
Now, if we consider both the macrocyclic inputs, “Input CTAB” and “Input β-CD” together and the fluorescence responses at 416 nm as the optical output, an “IMPLICATION” (a combination of NAND and NOT logic gates) logic gate could be constructed (Table 2 and Fig. 3). Here, “Input CTAB” and NOT output of “Input β-CD” were considered as the inputs of NAND gate and produced the final output at 416 nm. Fig. 3a undoubtedly portrayed the optical responses through a bar
presentation with indicated “ON” and “OFF” differentiated by a threshold. Fig. 3b presented the primary layout of the conventional IMPLICATION logic gate with chemical inputs and fluorescence output at 416 nm.
Fig. 3. (a) Bar presentation of optical responses received at 416 nm for HM and after interaction with CTAB and β-CD sequentially; (b) Corresponding IMPLICATION logic layout derived from the fluorescence responses at 416 nm.
Fig. 4. (a) Bar presentation of optical responses received at 365 nm for HM and after interactions with CTAB and β-CD sequentially; (b) Corresponding INHIBIT logic layout derived from 365 nm responses. Fluorescence response at 365 nm of HM was only switched on in presence of CTAB, in absence of βCD (Fig. 1). For remaining situations i.e., in absence of CTAB, in presence of β-CD, in simultaneous absence or presence of both the stimuli, no characteristic fluorescence at 365 nm was observed. Here, only one of the active inputs specifically inhibited the output response. By applying proper threshold on these results, generated the truth table (Table 2) which resembled that of an “INHIBIT” logic gate (Fig. 4) integrating “AND” and “NOT” logic functions. “Input CTAB” and NOT output of “Input βCD” acted as two inputs of an AND gate, giving final “INHIBIT” function at 365 nm fluorescence channel. In this way, complementary IMP/INH logic devices could easily be designed based on the fluorescence switching between different prototropic forms of HM. A generalized scheme of the operational patterns of logic gates on the molecular platform of HM is given below (Scheme 2):
Scheme 2. Operational principle of multiple logic gates on the molecular platform of HM. 3.3 Memory device Current research in molecular computing arena is completely focused on the design of smart devices at the molecular scale. In order to process and store information, molecular memory modules would be a vital part of such smart devices. Although current silicon based storage devices are gratifying the storage demands with acute efficiency, however, if compared with the molecular devices, their sizes are extremely large. Moreover, in the molecular photonic memory devices poses several advantages over the electronic silicon based devices like, lowest energy loss through dissipation of energy as heat, lowest chances of data loss through crosstalk, highest data transmission speed due to shortest switching time, more compact design and many more. With these possibilities, “molecular memory modules” is going to revolutionize the structural basis for the future data storage devices. There are many reports of molecular memory devices based on ions or molecules as inputs. Although, memory device based on macrocyclic components as inputs are hardly reported. Fluorescence responses of the reversible switching of cationic and neutral forms of HM were employed here to design a memory device for the information storage at the molecular level. Amusingly, HM displayed both “Erase-Read-Write-Read” and “Write-Read-Erase-Read” type binary logic functionalities at two different emission channels (416 nm and 365 nm respectively) based on the macrocyclic inputs, CTAB and β-CD (Fig. 5). After extensive literature review, we realised the fact that this is the first report of such macrocyclic based supramolecular memory device operated through two complimentary memory units. Interestingly, we could easily switch from one state to another (OFF to ON and vice-versa) by simple optical switching, without further addition of macrocyclic components. Advantages of this proposed memory device on HM are well reflected by its ruggedness, optical and thermal stability at ambient temperature. Working mechanism of this device is as follows: The ‘high’ and ‘low’ fluorescence intensities were labelled with the ‘ON’ (Output = 1) and the ‘OFF’ state (Output = 0) respectively through applying proper threshold gate at the specified wavelength. ‘Input CTAB’ acted as the ‘reset’ key for 416 and the ‘set’ key for 365 nm output channels.
Simultaneously, the macrocyclic ‘Input β-CD’ acted as the ‘set’ key for 416 nm and ‘reset’ key for 365 nm emission channel. HM acted as the device for both the states.
Fig. 5. Design of the molecular memory device based on optical switching of HM upon addition of macrocyclic inputs (CTAB and β-CD) with both “Erase-Read-Write-Read” and “Write-Read-EraseRead” type memory units functioning simultaneously at 416 nm and 365 nm respectively. 3.4 Supramolecular keypad lock Current electronic security devices are found to be well capable for information protection purposes. However, sometimes these devices are hacked by intruders. Major drawback of the electronic security devices are the limited number of characters and their combinations for password composition. While, the opto-chemical keypad locks are expected to provide enormous security supported by the limitless hard-to-reveal optical-chemical possibilities and their combinations. These features promote the optochemical security devices as more complex and rigid to crack over the conventional electronic password protection systems. In this report, we proposed a potential molecular keypad lock utilizing macrocyclic components, CTAB and β-CD along with excitation light of 300 nm as “Input keys”. Our proposed supramolecular lock is operated through correct and sequential entry of opto-chemical password keys. The key ‘C’ and ‘B’ represented as addition of macrocyclic components, CTAB and β-CD respectively. In order to open the lock, one needs to know the exact input key sequence of the password to open the lock (Fig. 6).
Fig. 6. Operation of the supramolecular keypad lock upon application of the corresponding inputs (‘U’: excitation wavelength of 300 nm; ‘C’: CTAB; ‘B’: β-CD). The output is read as the change of the fluorescence intensity at 365 nm. Solid line shows the set threshold. Here, we detailed the operational mechanism of our proposed opto-chemical keypad lock. There are six possible usable passwords, composed (as the combinations of) of three characters input keys (‘C’, ‘B’ and ‘U’) without repetition; i.e., ‘CBU’, ‘BCU’, ‘UCB’, ‘UBC’, ‘BUC’, and ‘CUB’. The keypad lock responses whether the password is correct or not after the user completes the three-digit entry of password keys. Incomplete entry of the password leaves the lock non-responsive. Therefore, the enduser must press the three distinct keys to receive the final response from the lock, whether the entered password is correct or not. Here, the excitation light (‘U’) is treated as an active input key. After pressing the input key ‘U’, irrespective of its position in the character sequence of a password (1st, 2nd, or 3rd), the fluorescence intensity (FI) at 365 nm for the present chemical system and is recorded and memorized in the recorder until the completion of the password entry and finally considered as the output response to operate the lock. Hence, any entry after pressing ‘U’ is considered as the false entry. For example, if we consider ‘UCB’ and ‘UBC’ as passwords, as ‘U’ is pressed in the first step of the password entry, the recorded FI of the pure HM at 365 nm is memorised and considered as the output response to open the lock just after the completion of the whole password entry. Once the password entry is being completed, as the FI from HM at 365 nm is well below the threshold, the system would response in such a way that the password is incorrect and the system would remain at locked state. Similarly, for ‘CUB’ password, after entering the character ‘U’, the emission intensity of HM-CTAB solution is measured and recorded. Finally, pressing of the key ‘B’ completes the correct password entry and the lock opens. For the password, ‘CUB’, the effective entry is ‘CU’ but to complete the operational criteria of the lock and to receive final response, the end-user must need to press ‘B’ at the end of the password entry. Among these six possible passwords, only the ‘CUB’ provides strong FI at 365 nm and crosses the preset threshold value to open the lock. Such a designing of the macrocyclic components based keypad lock might find its future application in information protection and related fields.
4. Conclusion Based on the photoswitching of the active anticancer agent (HM), we are reporting a molecular logic system composed of dual macrocyclic chemical inputs. The developed systems could be easily tuned to integrate multiple functionalities that could directly modulate the optical signals via macrocyclic components regulatory switch. A specific logic response would be extremely effective to isolate the real active form (neutral or cationic) of HM and monitor its biological or therapeutic activity. This molecular logic based approach is a proof of concept that might provide an effective model from which other bioanalyte recognition systems could be designed. Moreover, the present approach could be treated as a general route that the molecules like HM having both acidic as well as basic moieties in a conjugated system (like others members of the β-carboline family like harmane, norharmane etc.) are expected to display similar logic behaviors upon interaction with these macrocyclics. Finally, here we designed a molecular memory device that operates through both-way memory units as well as a keypad lock operated through macrocyclic components.
Acknowledgement Research reported in this article was financially supported by the Department of Science and Technology, Govt. of India, New Delhi, under the award number of DST YSS/2015/000904, dated 17-Nov-2015 sanctioned to Dr. Tapas Majumdar. Monaj Karar gratefully acknowledges CSIR, Govt. of India, New Delhi, for his Senior Research Fellowship (SRF). Provakar Paul sincerely acknowledges CSIR, Govt. of India, New Delhi, for his Junior Research Fellowship (JRF). Conflicts of interest “There are no conflicts to declare.”
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Dual Macro-cyclic Component Based Logic Diversity
Macrocyclic component regulated unique reversible photoswitching of potent anticancer drug harmine plays the important role in capturing the final output of the logic functions. Promising functional properties of HM and macrocyclic components (micelles and β-CD) in terms of molecular logical view might be utilised to isolate the exact structural form of the biologically active HM molecule. Additionally, as a proof of principle we could say that molecules with similar functionalities like HM supposed to display similar logic response variations with indicated macrocyclics.
Research Highlights •
The present research highlights a new model of designing of special logic circuits, memory device as well as molecular lock directed by dual macrocyclic components
•
The developed systems are easily tuned to integrate multiple functionalities included into the sensor system which directly modulate the optical signal via macrocyclic component regulatory switch.
•
Here for the first time we designed a memory device that operates through both way memory unit as well as a keypad lock operated through macrocyclic components.
Conflict of interests
“There are no conflicts to declare.”
S0143-7208(19)32038-8
DOI:
https://doi.org/10.1016/j.dyepig.2019.108060
Reference:
DYPI 108060
To appear in:
Dyes and Pigments
Received Date: 29 August 2019 Revised Date:
11 November 2019
Accepted Date: 18 November 2019
Please cite this article as: Karar M, Paul P, Paul S, Haldar B, Mallick A, Majumdar T, Dual macrocyclic component based logic diversity, Dyes and Pigments (2019), doi: https://doi.org/10.1016/ j.dyepig.2019.108060. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.
Dual Macro-cyclic Component Based Logic Diversity Monaj Karara, Provakar Paula, Suvendu Paula, Basudeb Haldarc, Arabinda Mallick*b, Tapas Majumdar*a a
Department of Chemistry, University of Kalyani, Nadia, West Bengal, 741235, India
b
Department of Chemistry, Kazi Nazrul University, Asansol, West Bengal, 713340, India
c
Department of Chemistry, Vivekananda Mahavidyalaya, Burdwan, West Bengal, 713103, India
E-mail AM: [email protected]; TM: [email protected]
Abstract In continuation of our recent studies on the photophysics of a photodynamic therapeutic agent, harmine (HM) in model membrane, the present contribution highlights a new model to design multiple logic circuits, a memory device and a molecular lock regulated by dual macrocyclic components as chemical inputs. The unique reversible photoswitching regulated by macrocyclic components plays decisive role in the manifestation of the final outputs for the logic functions. Inspired by this phenomenon, herein, we are reporting the use of a photosensitizer molecule for designing of various logic circuits at molecular level with the intention to escalate the next generation molecular logic arena. For these desired outsets, fluorescence spectroscopic changes of HM upon addition of macrocyclic components (CTAB and β-CD) were utilized. Beyond the simple single input single output logic gates (NOT, YES, PASS 0 and PASS 1), we were also able to design IMPLICATION and INHIBIT gates. In addition to different logic functions, the modulations of the optical responses of HM driven by the macrocyclic components were employed to design “EraseRead-Write-Read” and “Write-Read-Erase-Read” type memory units. Moreover, considering the optical responses of HM we proposed a supramolecular keypad lock operated through unique sequential entry of opto-chemical passwords.
Keywords: Harmine, Keypad lock, Macrocyclics, Memory unit, Molecular logic gate. 1. Introduction Depending on the pH of the aqueous medium, most of the photosensitizer molecules might exist in four different prototropic forms (neutral, cation, anionic and zwitterion) in the electronic ground and excited states [1]. Use of photosensitizer molecules for the treatment of neoplastic diseases, generally known as photodynamic therapy (PDT), has become a topic of growing medical interest. PDT produces singlet oxygen that damages the cancer cells. This is a standard method for cancer treatment [2,3]. Over the last few decades, extensive preclinical and clinical research established HM (Scheme
1) as a potential anticancer agent [2-6]. In addition, HM exhibits strong medicinal activities towards tumour proliferation and inducing apoptosis [3]. Efficacy of the phototherapeutic action mainly depends on the bio-distribution of the probe molecule in the cytoplasmic and mitochondrial membranes, its retention and the nature of binding inside the target cells. Studies in living cells revealed that molecules belonging to this class exist both in neutral and protonated forms in the cytoplasm, whereas only in its protonated form inside the nucleus. As a matter of fact, the functions of these biologically active molecules are very much correlated with their structural forms [1,7]. Recently, studies on HM by Varela et al.[7] revealed that the neutral form of HM shows significant triplet state yield and this long-lived triplet state might play important role in their in vivo photosensitization reactions in presence of oxygen. This phenomenon could be accounted for strong anti-cancer activities of the neutral form of HM. Under this situation, it is very much logical to assume that, there must be some in-situ molecular mechanism to promote a particular prototropic form of probes like HM to achieve better biological efficacy in a specific environment. Logic gates evolved with a variety of applications that transformed the world through digitization. In many such logic gates, two binary inputs are converted to a single binary output and might be extended to develop a third logic gate by accepting the outputs as inputs. de Silva et al.[8] first proposed the idea of photonic logic device on the molecular platform. Till date, excellent researches came up with the development of molecular systems executing binary logic operations paving the path for the construction of simple and complex electronic or photonic driven systems and networks that function as molecular-level devices [9,10]. Besides, the uses of these logic operations based on simple host-guest complexation were well advanced for the sensing studies, drug delivery, theranostics, and materials chemistry [11-17]. Present molecular logic arena is based on designing of multiple logic gates on the unimolecular platform [18-24] in order to achieve functional complexity of integrated circuits beyond basic logic gates. There are many reports where multiple logic gates were designed on a unimolecular platform based on ions or/and molecules as chemical inputs [18-27]. Since the early report by de Silva et al.[28] to employ macrocyclic compound as molecular logic input, limited number of reports are available where macrocyclic components could replace the usual chemical inputs to construct molecular logic devices [29]. In continuation of our earlier report [30] on HM, we planned to execute the unimolecular platform of HM for the designing of multiple logic gates employing the macrocyclic components as chemical inputs. Among many possibilities, different sets of input-output combinations were compiled to mimic the basic binary operations of multiple and fully different logic gates. Now, it will be extremely helpful to predict the exact prototropic form of HM present inside the cell, based on the specific logic function generated for a particular set of inputs. We could assume that the molecules like HM and other members of β-carboline family containing acidic pyrrolic hydrogen as well as a basic pyridinic nitrogen (Scheme 1) supposed to display similar kind of optical responses upon interactions with these macrocyclic components like micelles and β-cyclodextrin (β-CD). Therefore,
this report represents a general route for the designing of multiple logic gates of a class of molecules upon sequential interaction with these macrocyclics. In recent times, scientists have been devoting enormous efforts to design molecular keypad locks based on the chemicals as well as optical parameters as inputs. In this regard the development of a supramolecular keypad lock by Pischel et al. [31] is remarkable. In this report, we designed a supramolecular keypad lock considering macrocyclic components along with excitation light as input keys that operate the lock.
Scheme 1. Molecular structure of Harmine.
2. Materials and methods HM and β-CD were procured from Aldrich (Missouri, USA) and used as received. The surfactant, CTAB was procured from Lancaster (England) and used as received. Spectroscopy grade water from Millipore was used throughout the experiment. Steady-state fluorescence experiments were carried out on Hitachi F-7000 spectrofluorometer (Tokyo, Japan). Slit ratio was kept to 1 (Ex slit = 5 nm, Em slit = 5 nm) and the PMT voltage was kept at 500V. A cuvette 10 mm width was used for fluorescence measurement. Initial concentration of HM was 0.335 mM. All the fluorescence measurements were after proper thermal equilibration of the solution in the quartz cuvette through properly stirred on a magnetic stirrer. Due to very low solubility of β-CD in water pre-weighted solid β-CD were added in the cuvette and stirred for the sufficient time to achieve a homogeneous thermally equilibrated solution. Temperature was kept constant at 300 K throughout the experiment.
3. Results and discussion 3.1 Photophysical studies Steady state fluorescence spectroscopic analysis of HM (Fig. 1) in aqueous and micellar environments was already discussed in our previous report [30]. However, for the general readership and to make the base to understand the logic diversity, we highlighted here the salient features of the steady state fluorescence results. Room temperature emission spectrum of the cationic form of HM in aqueous medium could be characterized by a slightly broad unstructured band with a maximum at around 416 nm. Gradual addition of CTAB to the aqueous solution of the probe led to the appearance of a band at 365 nm corresponding to the neutral species at the cost of that of the cationic species through a clear isoemissive point at around 400 nm. Dramatic changes of emission spectra upon addition of CTAB
indicated a structural switchover of HM through a dynamic equilibrium in the excited state. Interesting reverse switching of emission band from 365 to 416 nm was observed upon the addition of β-CD within HM-CTAB i.e., the cationic band at 416 nm was almost restored with the expense of neutral emission band at 365 nm. Summarized spectroscopic results were represented in Fig. 1.
Fig. 1. Individual fluorescence spectrum of HM and the resultant spectra of individual and sequential interactions of CTAB and β-CD with HM; temp. = 300 K
3.2 Application towards logic diversity Distinct optical responses of HM due to inter-conversion of cationic and neutral forms with sequential addition of CTAB and β-CD were compiled to mimic quite a few truth tables of corresponding logic gates. Fluorescence spectral responses of HM at 416 nm or 365 nm were considered as “output” to generate the truth tables (Table 1 and 2). For both the emission channels, a threshold value of emission intensity was set, above which the binary value was considered as “1” and below as “0” respectively. Considering HM or HM-CTAB as distinct devices and employing CTAB or β-CD as single chemical input, we were able to construct single output based “NOT”, “YES”, “PASS 0” and “PASS 1” gates at the 365 and 416 nm optical output channels. In addition, on the unimolecular platform of HM, engaging both chemical inputs we designed “IMPLICATION” and “INHIBIT” logic gates. The binary responses of the “INHIBIT” logic gate is complementary to an “IMPLICATION” gate and the function is quite similar to that of IF-THEN and NOT operations. Considering HM as device and CTAB as the single chemical input, a “NOT” logic was designed at 416 nm optical response as primary output. Now, this system will act as a “YES” logic gate if we monitor the optical output at 365 nm (Table 1a and Fig. 2a & 2b). Table 1. Construction of truth tables for NOT, YES, PASS 0 and PASS 1 logic gates based on fluorescence responses of HM with CTAB and β-CD (colours (synchronized with the Figure 1) in the rows represents the resultant states generated after the chemical input.
Similarly, if we consider HM-CTAB as the main chemical device another pair of YES and NOT logic gate could be designed. Interestingly, for HM-CTAB device optical output channels for YES and NOT logic gates were completely inverse to that of HM as device i.e., YES gate at 416 nm and NOT gate at 365 nm output channels (Table 1b and Fig. 2c & 2d).
Fig. 2. (a) NOT and (b) YES logic gate layouts considering HM as device; (c) YES and (d) NOT logic gate layouts considering HM-CTAB as device; PASS 0 (e) and PASS 1 (f) logic gate layouts based on HM as device. Another two “single input single output” logic gates i.e. “PASS 0” and “PASS 1” were designed on the unimolecular platform of HM considering β-CD as the single chemical input. The binary conversion of 365 nm and 416 nm emission channel responses exactly matched with the corresponding truth tables of the PASS 0 and PASS 1 logic gates respectively (Table 1, Fig. 2e & 2f). Table 2. Construction of truth tables based on fluorescence responses of HM upon interactions with CTAB and β-CD individually and sequentially.
Now, if we consider both the macrocyclic inputs, “Input CTAB” and “Input β-CD” together and the fluorescence responses at 416 nm as the optical output, an “IMPLICATION” (a combination of NAND and NOT logic gates) logic gate could be constructed (Table 2 and Fig. 3). Here, “Input CTAB” and NOT output of “Input β-CD” were considered as the inputs of NAND gate and produced the final output at 416 nm. Fig. 3a undoubtedly portrayed the optical responses through a bar
presentation with indicated “ON” and “OFF” differentiated by a threshold. Fig. 3b presented the primary layout of the conventional IMPLICATION logic gate with chemical inputs and fluorescence output at 416 nm.
Fig. 3. (a) Bar presentation of optical responses received at 416 nm for HM and after interaction with CTAB and β-CD sequentially; (b) Corresponding IMPLICATION logic layout derived from the fluorescence responses at 416 nm.
Fig. 4. (a) Bar presentation of optical responses received at 365 nm for HM and after interactions with CTAB and β-CD sequentially; (b) Corresponding INHIBIT logic layout derived from 365 nm responses. Fluorescence response at 365 nm of HM was only switched on in presence of CTAB, in absence of βCD (Fig. 1). For remaining situations i.e., in absence of CTAB, in presence of β-CD, in simultaneous absence or presence of both the stimuli, no characteristic fluorescence at 365 nm was observed. Here, only one of the active inputs specifically inhibited the output response. By applying proper threshold on these results, generated the truth table (Table 2) which resembled that of an “INHIBIT” logic gate (Fig. 4) integrating “AND” and “NOT” logic functions. “Input CTAB” and NOT output of “Input βCD” acted as two inputs of an AND gate, giving final “INHIBIT” function at 365 nm fluorescence channel. In this way, complementary IMP/INH logic devices could easily be designed based on the fluorescence switching between different prototropic forms of HM. A generalized scheme of the operational patterns of logic gates on the molecular platform of HM is given below (Scheme 2):
Scheme 2. Operational principle of multiple logic gates on the molecular platform of HM. 3.3 Memory device Current research in molecular computing arena is completely focused on the design of smart devices at the molecular scale. In order to process and store information, molecular memory modules would be a vital part of such smart devices. Although current silicon based storage devices are gratifying the storage demands with acute efficiency, however, if compared with the molecular devices, their sizes are extremely large. Moreover, in the molecular photonic memory devices poses several advantages over the electronic silicon based devices like, lowest energy loss through dissipation of energy as heat, lowest chances of data loss through crosstalk, highest data transmission speed due to shortest switching time, more compact design and many more. With these possibilities, “molecular memory modules” is going to revolutionize the structural basis for the future data storage devices. There are many reports of molecular memory devices based on ions or molecules as inputs. Although, memory device based on macrocyclic components as inputs are hardly reported. Fluorescence responses of the reversible switching of cationic and neutral forms of HM were employed here to design a memory device for the information storage at the molecular level. Amusingly, HM displayed both “Erase-Read-Write-Read” and “Write-Read-Erase-Read” type binary logic functionalities at two different emission channels (416 nm and 365 nm respectively) based on the macrocyclic inputs, CTAB and β-CD (Fig. 5). After extensive literature review, we realised the fact that this is the first report of such macrocyclic based supramolecular memory device operated through two complimentary memory units. Interestingly, we could easily switch from one state to another (OFF to ON and vice-versa) by simple optical switching, without further addition of macrocyclic components. Advantages of this proposed memory device on HM are well reflected by its ruggedness, optical and thermal stability at ambient temperature. Working mechanism of this device is as follows: The ‘high’ and ‘low’ fluorescence intensities were labelled with the ‘ON’ (Output = 1) and the ‘OFF’ state (Output = 0) respectively through applying proper threshold gate at the specified wavelength. ‘Input CTAB’ acted as the ‘reset’ key for 416 and the ‘set’ key for 365 nm output channels.
Simultaneously, the macrocyclic ‘Input β-CD’ acted as the ‘set’ key for 416 nm and ‘reset’ key for 365 nm emission channel. HM acted as the device for both the states.
Fig. 5. Design of the molecular memory device based on optical switching of HM upon addition of macrocyclic inputs (CTAB and β-CD) with both “Erase-Read-Write-Read” and “Write-Read-EraseRead” type memory units functioning simultaneously at 416 nm and 365 nm respectively. 3.4 Supramolecular keypad lock Current electronic security devices are found to be well capable for information protection purposes. However, sometimes these devices are hacked by intruders. Major drawback of the electronic security devices are the limited number of characters and their combinations for password composition. While, the opto-chemical keypad locks are expected to provide enormous security supported by the limitless hard-to-reveal optical-chemical possibilities and their combinations. These features promote the optochemical security devices as more complex and rigid to crack over the conventional electronic password protection systems. In this report, we proposed a potential molecular keypad lock utilizing macrocyclic components, CTAB and β-CD along with excitation light of 300 nm as “Input keys”. Our proposed supramolecular lock is operated through correct and sequential entry of opto-chemical password keys. The key ‘C’ and ‘B’ represented as addition of macrocyclic components, CTAB and β-CD respectively. In order to open the lock, one needs to know the exact input key sequence of the password to open the lock (Fig. 6).
Fig. 6. Operation of the supramolecular keypad lock upon application of the corresponding inputs (‘U’: excitation wavelength of 300 nm; ‘C’: CTAB; ‘B’: β-CD). The output is read as the change of the fluorescence intensity at 365 nm. Solid line shows the set threshold. Here, we detailed the operational mechanism of our proposed opto-chemical keypad lock. There are six possible usable passwords, composed (as the combinations of) of three characters input keys (‘C’, ‘B’ and ‘U’) without repetition; i.e., ‘CBU’, ‘BCU’, ‘UCB’, ‘UBC’, ‘BUC’, and ‘CUB’. The keypad lock responses whether the password is correct or not after the user completes the three-digit entry of password keys. Incomplete entry of the password leaves the lock non-responsive. Therefore, the enduser must press the three distinct keys to receive the final response from the lock, whether the entered password is correct or not. Here, the excitation light (‘U’) is treated as an active input key. After pressing the input key ‘U’, irrespective of its position in the character sequence of a password (1st, 2nd, or 3rd), the fluorescence intensity (FI) at 365 nm for the present chemical system and is recorded and memorized in the recorder until the completion of the password entry and finally considered as the output response to operate the lock. Hence, any entry after pressing ‘U’ is considered as the false entry. For example, if we consider ‘UCB’ and ‘UBC’ as passwords, as ‘U’ is pressed in the first step of the password entry, the recorded FI of the pure HM at 365 nm is memorised and considered as the output response to open the lock just after the completion of the whole password entry. Once the password entry is being completed, as the FI from HM at 365 nm is well below the threshold, the system would response in such a way that the password is incorrect and the system would remain at locked state. Similarly, for ‘CUB’ password, after entering the character ‘U’, the emission intensity of HM-CTAB solution is measured and recorded. Finally, pressing of the key ‘B’ completes the correct password entry and the lock opens. For the password, ‘CUB’, the effective entry is ‘CU’ but to complete the operational criteria of the lock and to receive final response, the end-user must need to press ‘B’ at the end of the password entry. Among these six possible passwords, only the ‘CUB’ provides strong FI at 365 nm and crosses the preset threshold value to open the lock. Such a designing of the macrocyclic components based keypad lock might find its future application in information protection and related fields.
4. Conclusion Based on the photoswitching of the active anticancer agent (HM), we are reporting a molecular logic system composed of dual macrocyclic chemical inputs. The developed systems could be easily tuned to integrate multiple functionalities that could directly modulate the optical signals via macrocyclic components regulatory switch. A specific logic response would be extremely effective to isolate the real active form (neutral or cationic) of HM and monitor its biological or therapeutic activity. This molecular logic based approach is a proof of concept that might provide an effective model from which other bioanalyte recognition systems could be designed. Moreover, the present approach could be treated as a general route that the molecules like HM having both acidic as well as basic moieties in a conjugated system (like others members of the β-carboline family like harmane, norharmane etc.) are expected to display similar logic behaviors upon interaction with these macrocyclics. Finally, here we designed a molecular memory device that operates through both-way memory units as well as a keypad lock operated through macrocyclic components.
Acknowledgement Research reported in this article was financially supported by the Department of Science and Technology, Govt. of India, New Delhi, under the award number of DST YSS/2015/000904, dated 17-Nov-2015 sanctioned to Dr. Tapas Majumdar. Monaj Karar gratefully acknowledges CSIR, Govt. of India, New Delhi, for his Senior Research Fellowship (SRF). Provakar Paul sincerely acknowledges CSIR, Govt. of India, New Delhi, for his Junior Research Fellowship (JRF). Conflicts of interest “There are no conflicts to declare.”
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Dual Macro-cyclic Component Based Logic Diversity
Macrocyclic component regulated unique reversible photoswitching of potent anticancer drug harmine plays the important role in capturing the final output of the logic functions. Promising functional properties of HM and macrocyclic components (micelles and β-CD) in terms of molecular logical view might be utilised to isolate the exact structural form of the biologically active HM molecule. Additionally, as a proof of principle we could say that molecules with similar functionalities like HM supposed to display similar logic response variations with indicated macrocyclics.
Research Highlights •
The present research highlights a new model of designing of special logic circuits, memory device as well as molecular lock directed by dual macrocyclic components
•
The developed systems are easily tuned to integrate multiple functionalities included into the sensor system which directly modulate the optical signal via macrocyclic component regulatory switch.
•
Here for the first time we designed a memory device that operates through both way memory unit as well as a keypad lock operated through macrocyclic components.
Conflict of interests
“There are no conflicts to declare.”