TD-DFT investigation on anion recognition mechanism of anthraldehyde-based fluorescent thiosemicarbazone derivatives

The mechanism of host–guest interaction of receptors towards fluoride ion has been investigated using computational methods. To distinguish the effect of aromaticity in host–guest interaction, we investigated unsubstituted (ATSC) and phenyl-substituted (APTSC) anthracene thiosemicarbazones towards different ions. In the ground state of receptor-fluoride complex, the added fluoride ion made hydrogen bond through N − H…F…H − N, whereas the intramolecular hydrogen bonding was through F − H…N in the excited state of receptor-fluoride complex. Experimental absorption and emission spectra were well reproduced by the calculated vertical excitation energies. The transition state (TS) calculations were performed to understand the thermodynamic features and mechanism of host–guest interaction. The natural bond orbital analyses show that the second perturbation energy for donor–acceptor interaction of F− with hydrogen is more than 300 kcal/mol−1 at the excited state of receptor-fluoride complex, which indicates the strong single bond between fluoride and hydrogen atom. The PES scan confirms that deprotonation took place at the excited state of receptor-fluoride complex. The results indicate the excited-state proton transfer (ESPT) process from N–H group nearby the anthracene moiety. The APTSC is a better chemosensor than ATSC. This infers that the aromaticity will increase the efficiency of fluorescence receptor towards fluoride ion. A schematic representation of sensing mode of anthracene-based thiosemicarbazones toward fluoride ion. The fluoride ion first makes a hydrogen bond with NH proton nearby anthracene moiety. The excited state proton transfer mechanism was confirmed by PES and NBO studies.


Introduction
In view of the fact that ions play a major role in many chemical and biological process, designing ion selective molecular sensors is a challenging entity in supramolecular chemistry [1,2]. Fluoride ion is a necessary trace element in the human body, which has vital role in a broad range of chemical, biological and environmental processes [3][4][5]. The excessive absorption of fluoride ion can cause fluorosis of bone, immune system disruption, urolithiasis, kidney damage and cancer [6]. It has one of the most perplexing ion recognition, due to its high electronegativity and hydration enthalpy [7]. The detection of fluoride ion can prevent and cure dental problems and osteoporosis [8]. There are many experimental reports as molecular optical sensors, whilst very few reports of selective fluorescence fluoride sensor are seen, due to the surface charge density and similar basicity of fluoride ion with other ions [9][10][11][12].
The theoretical characteristic and the detailed investigation of host-guest mechanism is perilous for fluorescent chemosensor. Based on the experimental results, researchers have proposed several categories of signalling mechanisms for fluoride chemosensor, such as photo-induced electron transfer (PET), intramolecular charge transfer (ICT), excimer and exciplex formation, metal ligand charge transfer (MLCT) and excited-state intramolecular proton transfer. [13][14][15][16]. Amongst these, the ESPT performs dynamic role in determining the photophysical and photo-chemical properties of organic molecules, which usually shows dual fluorescence behaviour [17,18]. The PET mechanism was used to describe the hydrogen bonding, in which enhancing or quenching corresponds to red or blue shifts in the absorption spectra [19][20][21]. Iverson and others demonstrated that charge transfer and π-π stacking interactions between a colourless guest and electron-rich aromatic rings produce coloured donor-acceptor complexes [22].
Amongst the chemosensors, fluorescent chemosensors have many advantages such as ease of detection, low cost, high sensitivity and biologically appropriate diagnostic tools. Recently, Udayakumari et al. reported APTSC as selective chemosensor for fluoride ion over other anions [23]. Taking this system as an example, herein we investigated the sensing mechanism of fluoride ion theoretically. The sensing mechanism of ATSC receptor was also investigated to evaluate the effect of aromatic group in sensing process. By using computational methods, we investigated the host-guest interaction of fluorescent thiosemicarbazones with anthraldehyde as receptors, which contain electron-rich aromatic rings. Furthermore, by comparing the results, we suggested that the aromaticity of the receptor will enhance the chemosensing behaviour.

Computational methods
The hybrid density functional theory (DFT) and Time Dependent DFT (TD-DFT) calculations were performed using Gaussian 09 programme. Optimizations have been carried out without symmetry constraints. The ground state of the receptors, receptor-fluoride complexes and deprotonated receptors were optimised using the hybrid B3LYP functional with 6-31G(d,p) basis set, whereas the optimization of excited state geometries were calculated using Handy and co-workers long-range modified version of B3LYP casted as Coulomb-attenuating method (CAM) hybrid function with long-range corrections (CAM-B3LYP) [24]. The vertical state excitation calculations were employed for the calculation of excitation state. The Polarised Continuum Model (PCM) with dimethyl sulfoxide solvent (dielectric constant = 46.826) calculation was implemented throughout the steps to include the solvent effect. To verify the ground state and excited state, optimised geometries are in local minima, and the vibrational frequency calculations were run for all the optimised structures. In order to understand and verify the nature of transition state and intermediate structures, the transition state (TS) and intrinsic reaction coordinate (IRC) calculations were carried out. The natural bond orbital (NBO) analyses were carried out at ground state and excited state structures of receptor-fluoride complexes to understand the charge distribution and energy of bonding and anti-bonding orbitals. The second order Fock matrix calculations were carried out to estimate the host-guest interactions [25,26]. The ESPT mechanism was confirmed with potential energy surface (PES) analysis [27].   In the ground state of APTSC, the dihedral angle between C5 − C4 − N3 − N2 was 34.39°. The dihedral angle between anthracene moiety and imine group was 115.99 and 1.248 for APTSC and ATSC receptors, respectively. These results revealed that the receptors, APTSC and ATSC, were not in coplanar. The N1 − H1 and N2 − H2 bond distance in APTSC is found to be 1.01 and 1.02 Å, respectively. The bond angle between C1-N1-C2 is 130.90°. The C-N bond distance in the APTSC is 1.28 Å. However, in the case of excited state of APTSC-F complex, the C-N bond distance found is 1.32 Å, The high bond length points the formation of single bond between C-N. In the ground state of receptorfluoride complex, the bond distance between F-H1 and F-H2 was found in the range of 1.50 and 1.46 Å, which indicated that the fluoride ion made hydrogen bond with receptor via N − H … F … H − N. The dihedral angles between phenyl group, imine group and anthracene moiety-imine group were found same in the APTSC and APTSC-F complex.

Geometric studies
In the excited state of APTSC-fluoride (APTSC-F*) complex, the calculated dihedral angle between anthracene moiety and imine group is 159.81, which is higher than the ground state structure of APTSC-F complex. In the APTSC-F*, the bond distance between F − H1 and F − H2 is found to be 1.91 and 0.99 Å, respectively. The lower bond length between fluoride and H2 implies the presence of strong bond between them, which indicates the proton transfer happened at excited state. Whilst in the case of excited state ATSC − F (ATSC − F*) structure, the F − H1, F − H2, N − H1 and N − H2 bond distance is calculated as1.97, 1.05, 1.01 and 1.40 Å, respectively. The higher bond distance between N-H2 and lower bond distance between F-H2 imply the deprotonation happened first at 'H2' proton of ATSC. Hence, it is evident of the excited state proton transfer (ESPT) process. The dihedral angle between anthracene moiety and imine group was twisted to 28.680° in ATSC − F*, which provides higher planarity and conjugation than pure receptor. The extension of the conjugation might help to delocalize the negative charge of the fluoride ion; hence, the photophysical property of the receptor-F complex varies from pure receptor.

Absorption and molecular orbital analysis
The absorption spectral studies were carried out for receptors and receptor-fluoride complexes to understand the change in optical behaviour in the host-guest process. The molecular orbitals involved in the major electronic transitions with the largest oscillator strength are shown in Figs. 3 and 4. Theoretical calculations predict six absorption transitions for each compound, and the dominant absorption transition of APTSC, APTSC-F complex, ATC and ATSC-F complex are given in Tables 3 and 4. The intense absorption transition for APTSC is calculated at 367.48 nm, with large oscillating strength 0.2957, which is assigned as π → π* transition from the highest occupied molecular orbital (HOMO, H) to the lowest unoccupied molecular orbital (LUMO, L). In HOMO, the electron delocalized over anthracene moiety and imine group, whereas in LUMO, the electron cloud only delocalized at anthracene moiety. The second dominant absorption peak was at 310 nm, which corresponds to HOMO, third lowest unoccupied molecular orbital (LUMO + 2, L + 2), where the electron delocalized throughout the anthracene moiety. Whilst in APTSC-F complex, the absorption peak at 367 nm decreases and accompanies with the formation of a new band at 374 nm. The high oscillating strength and percentage π → π* transition were between HOMO to LUMO. In the HOMO of APTSC-F complex, the electron was delocalized only on imine group, whereas the electron was delocalized on anthracene moiety in LUMO.
In the case of ATSC, the high oscillated frequency wavelength at 411 nm with 3.0136 eV energy. The high percentage orbital transition was in between HOMO-1 and LUMO. The second major absorption transition was at HOMO to LUMO orbitals. In HOMO, the electrons delocalized in anthracene moiety and thiosemicarbazide group, whilst the HOMO-1 and HOMO-2 orbitals had electron cloud only on imine group, not in anthracene moiety, whereas in LUMO, LUMO + 1 and LUMO + 2 orbitals, the electron clouded only at anthracene moiety. The resulting electron cloud rearrangement is cause for the changes in the photophysical properties of receptor in the host-guest interaction. Figure 5 displays the calculated orbital energies of APTSC and APTSC-F complex. The energy gap between HOMO and LUMO orbitals in emission profile is higher than that of absorption profile. The complete charge separation from thiosemicarbazone group to anthracene in the relaxation process is in good accordance with the definition of PET. The absorption profiles are calculated using the Gaussian models and compared with the experimental results.

Emission spectral analysis
To confirm the ESPT mechanism in chemosensing, the geometries at the ground state and excited states of both receptors (ATSC and APTSC) and receptor-F complexes were optimised. The fluorescence spectral analysis was performed in detail using six step vertical excited energy calculations. The emission spectra of APSTC and APSTC-F complex are shown in Fig. 6. The ground state energies of ATSC and APTSC are − 739,686.293 and − 884,475.883 kcal/ mol −1 , respectively, whereas the energies are very much higher in excited state, which are found to be − 802,369.249 and − 947,168.814 kcal/mol −1 for ATSC-F and APTSC-F complexes, respectively. It exhibits in S7 that the receptorfluoride complexes have less oscillator strength than corresponding receptors. The experimental emission peak of APTSC and APTSC-F complex was observed at 475 and 495 nm, whereas the calculated fluorescence peak was observed at 461 and 478 nm, respectively. The receptors ATSC and APTSC show low energy emission peak at 455 and 461 nm, respectively, which assign to π-π* transition of anthracene moiety, whereas the corresponding fluoride complexes, such as ATSC-F and APTSC-F, exhibit very intense emission peaks at 464 and 478 nm, respectively. The red shift in the fluorescence peaks after the addition of fluoride ion confirms sensing behaviour of the receptors. The intense red shift in the fluorescence spectra infers that the presence of fluoride ion extends the conjugation behaviour of receptors. For both receptors (ATSC and APTSC), the intense

Natural bond orbital (NBO) calculation
Natural bond orbital (NBO) analysis provides the most accurate possible 'natural Lewis structure' picture, because all orbital details are mathematically chosen to include the highest possible percentage of the electron density. Further confirming the ESPT process and the deprotonation of H2 from receptor via hydrogen bond, the NBO analysis was carried out at the ground state and excited state of receptor-fluoride complex. The binding energy (ΔE) between the binding sites of fluoride ion and the residue for receptor plays an important role in revealing the ability for fluoride anion to attach proton. The binding energies between the two segments separated by H1 − F and H2 − F of receptor-fluoride complexes were calculated. The second-perturbation energy of APTSC with fluoride ion suggested that the formation of intermolecular hydrogen bond between host and guest molecules and the energy details are listed in Table 5. The natural atomic hybrid calculation gave the bond order on each hybrid atoms. The hybridisation with single bond between N25 − H41 and N27 − H42 is listed in S3. In ground state APTSC-F complex, sp 3 nitrogen was hybridised to 's' hydrogen, but this bond was not in excited state. Resulting, a strong host-guest interaction between fluoride ion and APTSC occurred, which can be treated by the second-perturbation energy E(2). The interaction between host and guest can be explained by using second perturbation energy, which has been calculated using the equation, is the second perturbation energy, F ij is the off-diagonal element in the NBO Fock matrix, q i is the donor orbital occupancy and εi and εj are orbital energies. The NBO characters in ground state and excited state of ATSC-F complex are given in the S4. The σ-σ* and n-σ* host-guest interactions were seen at the ground state and excited state of ATSC − F and APTSC − F complexes. In the ground state, two modes of interactions were presented via fluoride to N25 − H41 and N27 − H42, whereas the excited state had only one interaction, which was via fluoride ion with H41. In the ground state of  receptor-fluoride complex, the second perturbation energies were varying from 0.3 to 44 kcal/mol −1 , which revealed that both the receptors make hydrogen bonding with fluoride ion in the ground state. But, the excited state of receptor-fluoride complexes has LP(F) → LP* (H41) interaction with more than 300 kcal/mol −1 energy, which shows that the fluoride ion makes strong bond with H(41) proton. This interaction generated from lone pair electron (n) of fluoride ion to n* of hydrogen (H41). The interactions were generated from core electron and lone pair electron. More overlap of the electron density confirms the strong donor-acceptor interactions; due to this, the H(41) preferred to interact with fluoride ion rather than H(43).

Potential energy curve of excited state geometry
To confirm the ESPT mechanism in host-guest interaction, the potential energy curve investigation of the ground state and excited state receptor-fluoride had been evaluated. The PES curve of APTSC-F complex in ground state and excited state is as shown in Fig. 9. is at nearby anthracene moiety and (N27) is nearby Phenyl group. The less energy was seen for the excited state N(25) − H(42) bond distance at 1.00 Å, and the same at ground state was more stable at 1.10 Å bond distance. These results confirm that the fluoride ion forms an intermolecular hydrogen bond with receptor's nitrogen (N2), which is the NH proton near by the anthracene moiety. In the host-guest interaction, the fluoride ion was first reacted with receptor and forms hydrogen bond via N − H … F, not in free H + ion. Hence, it shows a red shift in the fluorescence emission spectra and UV absorption spectra. This change in fluorescence colour signal can be directly detected with the naked eye. The potential energy curves of ATSC − F complex in ground state and excited state are as shown in S4.

Host-guest interaction
The hydrogen bond formation was confirmed in the ground state optimised structures of receptor-fluoride complexes, which has been defined as incipient proton transfer reaction from host to guest molecule. The reported experimental fluorescence quenching behaviour can be interpreted by the PET process when the fluoride anion is coordinated with APTSC. The fluorescence quenching was due to the electron transition from π-orbital of phenyl group to π -orbital of anthracene moiety. The optimised structure of receptor and receptor-fluoride complexes in the ground state and excited state suggested that the deprotonation took place at the excited state of receptor-fluoride complex, along the deprotonation that happened at the N − H proton nearby the anthracene moiety. The results from TS calculations, NBO and PES analyses confirm that the deprotonation takes place from the N-H proton, which is near by the anthracene moiety. The transition state and IRC studies confirmed the intermolecular hydrogen bond interaction between the fluoride ion with receptor. The shifts of the signals in absorption and emission spectra are prompted to enhance the strength of host molecules and result to increase the molecular conjugation when deprotonation happens. The great difference between fluorescent properties of the sensor can be used to recognise fluoride anions. The potential energy curve structure of receptor-fluoride in the ground state and the excited state defined the bond parameter for fluoride-sensing mechanism of receptor ATSC and APTSC. Figure 10 shows the sensing mechanism of receptors towards fluoride ion. The experimental absorption and emission spectra of APTSC receptor were well reproduced using TDDFT and vertical excited energy calculations from the optimised ground state geometries (receptor and receptor-F complex).

Conclusion
In summary, we have investigated the fluoride anion sensing mechanism of ATSC and APTSC receptors. The ground state and excited state geometry of receptors and receptor-fluoride complexes have been optimised. The experimental absorption and emission spectra are well reproduced by TDDFT and vertical transition energies computed from the ground state optimised geometries.