XRD Studies, Spectral Characteristics, TGA and DFT of 2,4-Diamino-6-phenyl-1,3,5-triazine: Phenylthioacetic Acid Cocrystal

The title compound was prepared crystallizing together the co-formers namely, 2,4-diamino-6phenyl-1,3,5-triazine (DAPT) and phenylthioacetic acid (PTAA) in methanol. The compound crystallized in the orthorhombic space group Pca21 with a = 12.384(2) Å, b = 18.698 (3) Å, c = 7.0428(11) Å, V = 1630.8(5) Å, and Z = 4. The compound existed as a 1:1 cocrystal. The dihedral Original Research Article Kumaresan et al.; AJOCS, 2(4): 1-11, 2017; Article no.AJOCS.32615 2 angle between the two formers is 50.89(9)°. The primary and secondary interactions between DAPT and PTAA form two different discrete chains C(3) that link the DAPT ribbons in adjacent layer. Mass spectra indicate the transfer of a carboxylic acid proton to form PTAA to the nitrogen of DAPT.


X-ray Structure
The crystal structures were determined using a BRUKER APEX 2 X-ray (three-circle) diffractometer. Intensity datasets were collected at room temperature on a BRUKER SMART APEXII CCD [16] area-detector diffractometer equipped with graphite monochromated Mo Kα radiation (λ = 0.71073 Å). The data were reduced using the program SAINT and empirical absorption corrections were carried out using the SADABS [16]. The structures were solved by  direct  methods  using  SHELXS-97  and  subsequent Fourier analyses, refined anisotropically by full-matrix least-squares method using SHELXL-97 [17] within the WINGX suite of software, based on F 2 with all reflections. All carbon-hydrogen's were positioned geometrically and refined by a riding model with Uiso1.2 times that of attached atoms. All non-H atoms were refined anisotropically. The molecular structures were drawn using the ORTEP-III [18] and POV-ray [19] programs.

Computational Methodology
All calculations were performed using Gaussian 09 software [20]. Gas phase geometry was fully optimized at Density Functional Theory (DFT/B3LYP-6-31G(d)) method. The electronic properties were calculated from the Koopmans' theorem and the molecular properties like geometry, total energy, molecular electrostatic potential, E HOMO , E LUMO , dipole moment, electron affinity, ionization potential, chemical potential, electronegativity, absolute hardness, softness, and nucleophilicity were carried out as reported [21].

IR Spectra
IR spectrum was recorded to confirm the transfer of carboxylic proton from PTAA to DAPT and also to identify the specific hydrogen bonds. If a proton transfer occurs from the acid to N of the base moiety, very broad peaks would appear around 2500±100 cm -1 . However, absence of any such band in the IR of the cocrystal is indicative of the nontransfer of proton from the acid to the base [22]. The IR spectrum of the cocrystal shows C=O stretching frequency at 1641cm -1 and -OH stretching frequency at 3214 cm -1 . There are significant variations in the stretching frequencies of -OH, C=N, and C=O groups compared to those of the cocrystal formers. Changes in the carbonyl frequencies in the crystal [23,24], in general, indicate the formation of the cocrystal. The C=O str of the cocrystal (1641 cm -1 ) shows a difference of 64 cm -1 from that of the free acid, PTAA (1705 cm -1 ). Thus it is understood that the C=O group is involved in H-bonding.

Mass Spectra
The ESI mass spectrum of DAPT:PTAA in negative ion mode shows the base peak at 167.04 (M+ • of PTAA is 168.04). This indicates the loss of an amu i.e. a proton from PTAA forming in to anion. The mass spectrum of DAPT:PTAA cocrystal in positive ion mode shows the base peak at 188.08 (M+ • of DAPT is 187.08). This is due to the acceptance of a proton from PTAA by DAPT. Thus the protonated DAPT appears at m/z 188.08 under the mass spectral conditions.

Thermogravimetric Analysis
TGA measurement of DAPT:PTAA shows that the cocrystal remains intact until 150°C. The first weight loss of 9.9% (calc.9.85%) may be due to the elemination of one each of NH 3 and H 2 O molecules at 125.8-141.3°C. The second stage decomposition of the cocrystal occurs between 160 and 270°C (66%). There is a gradual decomposition after 180°C-400°C. The cocrystal is thermally stable up to 180°C [25][26][27][28].

Single Crystal XRD Analysis of the Cocrystal DAPT:PTAA
Crystal Structure of DAPT:PTAA shows that the molecule crystallized in Pca2 1 space group existing as a 1:1 co-crystal. The chemical structure of DAPT:PTAA is given in Fig. 1 and ORTEP diagram and packing arrangement of the title compound are shown in Fig. 2. It consists of one molecule of 2,4-diamino-6-phenyl-1,3,5triazine (DAPT) and one molecule of 2phenylthioacetic acid (PTAA) in the asymmetric unit. The dihedral angle between the triazine moiety of DAPT and thioacetyl moiety of PTAA is found to be 50.89(9).  Twisting of the acid and 3° amino groups across the O-H···N hydrogen bond gives the neutralsingle interaction motif as shown below [29].
The crystal structure shows that there is no proton transfer from the carboxyl group of PTAA to the DAPT in the asymmetric unit. The predicted intermolecular hydrogen bonding motif N 2 -H-O 2 is observed between the nitrogen of DAPT and carboxyl group of PTAA. It could be noticed that steric requirements warrant the Hbonding to occur between N 2 and H-O 2 -and naturally the other nitrogens are spared. The crystal data collection and refinement details are presented in Table 1. When there is an insufficient pKa difference between the COOH and amino group, proton transfer does not occur to form any hydrogen bond such as N + -H---O. In the cocrystal, each DAPT molecule links two different PTAA molecules through O2-H...N2 and N4-H...O1 iii [symmetry code: 1/2-x, y, -1/2+z] hydrogen bonds. The dihedral angle between the phenyl ring and the thioacetyl group of PTAA is found to be 11.51 (11) Fig. 4 The two different discrete chains C(3) formed by the primary and secondary interactions between DAPT and PTAA molecules link DAPT ribbons in the adjacent layer. Twisting of the acid and 3° amino groups across the O-H···N hydrogen bond gives the neutralsingle interaction motif as shown below [29].

H-bondings
The crystal structure shows that there is no proton transfer from the carboxyl group of PTAA to the DAPT in the asymmetric unit. The predicted intermolecular hydrogen bonding motif N 2 -H-O 2 is observed between the nitrogen of DAPT and carboxyl group of PTAA. It could be noticed that steric requirements warrant the Hbonding to occur between N 2 and H-O 2 -and naturally the other nitrogens are spared. The crystal data collection and refinement details are presented in Table 1.   Fig. 4 The two different discrete chains C(3) formed by the primary and secondary interactions between DAPT and PTAA molecules link DAPT ribbons in the adjacent layer. Twisting of the acid and 3° amino groups across the O-H···N hydrogen bond gives the neutralsingle interaction motif as shown below [29].

H-bondings
The crystal structure shows that there is no proton transfer from the carboxyl group of PTAA to the DAPT in the asymmetric unit. The predicted intermolecular hydrogen bonding motif N 2 -H-O 2 is observed between the nitrogen of DAPT and carboxyl group of PTAA. It could be noticed that steric requirements warrant the Hbonding to occur between N 2 and H-O 2 -and naturally the other nitrogens are spared. The crystal data collection and refinement details are presented in Table 1.   Fig. 4 The two different discrete chains C(3) formed by the primary and secondary interactions between DAPT and PTAA molecules link DAPT ribbons in the adjacent layer.      (Fig. 4). The crystal structure is stabilized by the faceface π-π stacking force that is found between the parallel presence of triazine moiety of DAPT and the phenyl ring of PTAA.

Supplementary Information
The

Theoretical Studies
The DFT method represents good correlation between the calculated geometrical parameters and the single crystal XRD (SCXRD) data. This method also helps in the calculation of the other parameters for the acid (PTAA) and the cocrystal (DAPT:PTAA). Table 3 reveals that the geometrical parameters of theoretical studies are nearly the same as the experimental ones for the acid (PTAA) and the cocrystal (DAPT:PTAA). The acid (PTAA) and the cocrystal (DAPT:PTAA) have been studied theoretically in the absence of their SCXRD data using the B3LYP/3-21G(d) level of theory. Thus we have investigated the electronic structures of the acid (PTAA) and the cocrystal (DAPT:PTAA) using the DFT method. Fig. 5 shows the optimized structures of the acid (PTAA) and the cocrystal (DAPT:PTAA). Cocrystal (DAPT:PTAA) has lower energy (-1480.18eV) than the acid (PTAA) (-621.02eV) and triazine (-853.67) ( Table 3).

Frontier Molecular Orbitals
Frontier molecular orbital's (FMO) could provide information regarding the inverse dependence of stabilization energy on orbital energy difference. E HOMO is generally associated with the electron donating ability of a molecule. High values of E HOMO are likely to denote the tendency of the molecule to donate electrons to acceptor molecules of lower energy MO. E LUMO , indicates the ability of the molecule to accept electrons [34]. The binding ability of the molecule increases with increasing HOMO and decreasing LUMO energy values. Thus, the lower the value of E LUMO , the most probable it is that the molecule would accept electrons. Fig. 6 reveal the HOMO and LUMO of the cocrystal (DAPT:PTAA). From this results E HOMO and E LUMO value of the cocrystal is -5.6235 and -1.4171 respectively ( Table 3).
The difference between the HOMO and LUMO energy levels (DE) of the molecule is an important parameter determining the reactivity of the molecule. As DE decreases (especially for the cationic species), the reactivity of the molecule increases making the molecule less stable. Table 3 reveals that the HOMO-LUMO energy gap of the cocrystal (DAPT:PTAA) is lower than that of acid (PTAA) and triazine.
The dipole moment, which is defined as the first derivative of the energy with respect to an applied electric field, is mainly used to study the intermolecular interactions such as van der Waals type dipole-dipole forces etc. The larger the dipole moment, the stronger will be the intermolecular attraction [35]. The cocrystal (DAPT:PTAA) has higher dipole moment (3.1456 D) which reveals it to be more polar than the acid and triazine. Absolute hardness, η, and softness, σ, are important properties to measure the molecular stability and reactivity. A hard molecule has a large energy gap and a soft molecule has a small energy gap. Soft molecules are more reactive than hard ones because they could easily offer electrons to an acceptor. For the simplest transfer of electrons, absorption could occur at the part of the molecule where σ has the highest magnitude whereas η has the lowest [36]. The nucleophilicity, ω, measures the electrophilic power of a molecule. It has been reported that the lower the value ω, the lower the capacity of the molecule to donate electrons [37]. Table 3 shows that cocrystal (DAPT:PTAA) has moderate energy gap (ΔE, 4.2064 eV).
According to the molecular orbital (MO) theory, HOMO and LUMO are the most important factors affecting the bioactivity. The interaction between these molecules and the receptor of bacteria are correlated to π-π or hydrophobic interaction among these frontier molecular orbitals. If the charged parameters are responsible for antimicrobial activity of these molecules, then the negative charges mainly located on carbonyl Oatom may be said to interact with the positive portion of the receptor. The N-H and C-H, being the most positively charged parts, can interact with the negatively charged region of the receptor easily. We have finally resolved that the HOMO and LUMO of the cocrystal is mostly having π-antibonding type orbitals and thus, the electronic transitions from the HOMO to LUMO are mainly derived from the contribution of π-π  bands [38].

Mulliken Charge Analysis
Generally, Mulliken atomic charge calculation has an important application of quantum chemical calculations to molecular systems. It plays a vital role in the packing of crystals in the solid state by means of intermolecular interaction and it has significant influence on dipole moment, polarizability, electronic structure and vibrational modes [39]. The Mulliken charge analysis of molecules DAPT:PTAA are calculated at the HF and DFT/B3LYP levels for the molecule under study which are given in Table 4 and the corresponding population analysis graph are shown in Fig. 7.

CONCLUSION
The cocrystal 2,4-diamino-6-phenyl-1,3,5triazine:phenylthioacetic acid (DAPT:PTAA) has been prepared. The IR(KBr) of DAPT:PTAA indicates changes in the stretching frequencies of C=O group ascertaining the formation of the cocrystal. The recorded TGA of the cocrystal shows its thermal stability upto 180°C. The ESI mass spectra indicate that proton transfer does occur under mass spectral (ESI) conditions whereas the non transfer of proton from PTAA to DAPT happens at ambient conditions (as indicated by SCXRD). Single crystal XRD of DAPT:PTAA displays the presence of a neutralsingle interaction (OH…N) between the two molecules. Further the crystal structure of DAPT:PTAA is found stabilized by various Hbondings as well as π-π stackings.