Synthesis, growth, spectral studies, first-order molecular hyperpolarizability and Hirshfeld surface analysis of isonicotinohydrazide single crystals

Abstract

Single crystals of (E)-N′-((4-fluorophenyl)(phenyl)methylene)isonicotinohydrazide dihydrate were grown by the slow evaporation solution growth technique. The structure was elucidated by single crystal X-ray diffraction analysis and the crystal belongs to the triclinic system with the space group P1̄. The crystallinity of the material was confirmed by powder X-ray diffraction which coincides well with the simulated pattern with varied intensities. The band gap energy is estimated by the application of the Kubelka–Munk algorithm. Theoretical calculations were performed using density functional theory (DFT), to derive the optimized geometry, dipole moment, HOMO–LUMO energies and first-order molecular hyperpolarizability, β (∼84 times that of urea). The energy and oscillator strengths calculated by TD-DFT results complement the experimental findings. The atomic charge distributions of the various atoms were obtained by Mulliken charge population analysis. The molecular stability and bond strength were investigated by applying natural bond orbital analysis. Investigation of the intermolecular interactions and crystal packing via Hirshfeld surface analysis, based on single-crystal XRD, reveals that the close contacts are associated with molecular interactions. Fingerprint plots of the Hirshfeld surfaces were used to locate and analyze the percentage of hydrogen-bonding interactions. The grown crystals were further characterized by FT-IR, FT-Raman and TG/DTA.

---

1. Introduction

Organic single crystals possess unique optoelectronic properties because the molecules have delocalized electrons and exhibit various photoresponses such as photoconductive, photovoltaic, photocatalytic behavior and so on. Isoniazid, the hydrazide of isonicotinic acid is recognized as an effective antitubercular agent and is employed in the treatment and prevention of TB disease, not only as a single drug but also combined with others. The hydrazone group plays an important role in the antimicrobial activity and possesses interesting antibacterial, antifungal^1–3 and antitubercular activities.^4–9 In spite of the toxicity of repeated dosing, isonicotinylhydrazone (INH) is still considered to be a first line drug for chemotherapy of tuberculosis.¹⁰ Aromatic hydrazone molecules dispersed in a binder polymer are used as the main constituent of electrophotographic devices due to their excellent hole-transporting properties and relatively simple synthesis.^11–14 Recently, we have reported synthesis, growth, characterization and theoretical studies of 4-benzoylpyridine isonicotinyl hydrazone monohydrate,¹⁵ benzophenone-2-furoyl hydrazone¹⁶ and (E)-N′-(diphenylmethylene)isonicotinohydrazide dihydrate.¹⁷ The growth, structure and characterization of (E)-N′-((4-fluorophenyl)(phenyl)methylene)isonicotinohydrazide dihydrate (FPMI) have not been reported so far to the best of our knowledge. In the present study, we report the synthesis, growth, structure, optical, dipole moment, first-order molecular hyperpolarizability, Hirshfeld surface and fingerprint analysis of the organic crystal (E)-N′-((4-fluorophenyl)(phenyl)methylene)isonicotinohydrazide dihydrate. Experimental observations are mostly supported by theoretical studies.

2. Experimental

2.1. Synthesis and crystal growth

(E)-N′-((4-Fluorophenyl)(phenyl)methylene)isonicotinohydrazide dihydrate (FPMI) was synthesized by mixing stoichiometric amounts of p-fluorobenzophenone (Sigma Aldrich) and isoniazid (Sigma Aldrich) in the molar ratio of 1 : 1 (Scheme 1). The reactants were dissolved in ethanolic medium with a catalytic amount of concentrated sulphuric acid and refluxed for 3–5 h to form aryl acid hydrazone. The product formation was identified by thin layer chromatography. The reaction mixture was then poured into ice cold water and the precipitate obtained was filtered and dried. The purity of the compound was improved by successive recrystallization processes using ethanol as a solvent.

Scheme 1

2.2. Crystal growth

FPMI single crystals were grown by the slow evaporation solution growth technique at room temperature. A saturated solution of FPMI in ethanol was prepared and the solution was stirred for 2–3 h at room temperature to obtain a homogeneous solution. A beaker containing the solution was tightly covered with a thin polythene sheet to control the evaporation rate of the solvent and was kept undisturbed in a dust free environment. Numerous plate-like crystals were formed at the bottom of the container due to spontaneous nucleation. Macroscopic defect-free crystals were harvested after a period of 9 to 11 d and the photographs of the as-grown crystals are shown in Fig. 1.

Fig. 1 Photo images of as-grown FPMI crystals.

2.3. Computational details

Computational studies were done using the GAUSSIAN09W¹⁸ software package without any constraints on the geometry using density functional theory (DFT) and the molecules were visualized with the GAUSSVIEW 5.0 program.¹⁹ Hirshfeld surfaces and fingerprint plots were generated from the crystal data using the DFT method with 6-31G(d,p) as the basis set.²⁰

3. Results and discussion

3.1. FT-IR and FT-Raman

The characteristic vibrational bands observed in the FT-IR (experimental and theoretical) and FT-Raman spectra are shown in Fig. S1 and S2 (see ESI†). The molecular structure of FPMI consists of 44 atoms and 186 electrons and hence this molecule has 126 normal modes of vibration. The molecular conformation yielded by geometry optimization exhibits no special symmetries and hence the molecule belongs to the C₁ point group. The C=O stretching vibration is observed at 1672 cm⁻¹ (theoretically 1665 cm⁻¹). The C=N stretching vibration appeared as a sharp intensity band around 1600 cm⁻¹ (theoretically 1607 cm⁻¹). The absorption band around 1128 cm⁻¹ (theoretically 1127 cm⁻¹) corresponds to O=C–N stretching vibrations. The peak at 770 cm⁻¹ (theoretically 792 cm⁻¹) is due to aromatic C–H out of plane bending vibrations. The peak at 1034 cm⁻¹ (theoretically 1028 cm⁻¹) corresponds to C–F stretching vibrations. The observed FT-IR and FT-Raman vibrational bands of FPMI are listed along with literature^{15–17,21–24} data for some hydrazones as a comparative measure in Table 1.

Table 1 Observed vibrational bands of FPMI (cm⁻¹)

Assignments of vibration	FPMI		BPIH^a		BPFH^b	DPMI^c	PMBH^d		MPNH^e	MPINH^e
	FT-IR	FT-Raman	FT-IR	FT-Raman	FT-IR	FT-IR	FT-IR	FT-Raman	FT-IR	FT-IR
a Ref. 15.b Ref. 16.c Ref. 17.d Ref. 23.e Ref. 24.
C=O stretching	1672	1663	1672	1694	1687	1699	1697	1683	1637	1671
C=N stretching	1600	1601	1597	1599	1627	1639	1611	1627	1594	1647
C=C stretching	1507	1506	1507	1493	1513	1498	1582	1580	1548	1557
C–H stretching	3073	3072	3057	3061	3000–3100	3000–3100	3085, 3168	3100	3079	3026
N–H stretching	3452	—	3452	—	3351 and 3435	3427	3349	—	3444	3452
O=C–N stretching	1128	1130	1130	1133	1123	1118	—	—	—	—
C–F stretching	1034	1032	—	—	—	—	—	—	—	—

---

3.2. Optical studies

The Kubelka–Munk theory²⁵ provides a correlation between reflectance and concentration. The concentration of an absorbing species can be determined using the Kubelka–Munk formula,

F(R) = (1 − R)²/2R = α/s = Ac/s

where F(R) is the Kubelka–Munk function, R is the reflectance of the crystal, α is the absorption coefficient and s is the scattering coefficient, A is the absorbance and c is the concentration of the absorbing species. The direct and indirect band gap energies obtained from the intercept of the resulting straight lines with the energy axis at [F(R)hν]² = 0 and [F(R)hν]^1/2 = 0 are 3.21 eV (direct) and 2.96 eV (indirect) respectively as shown by the Tauc plots in Fig. S3.†

The optical absorbance spectrum of FPMI was recorded in the spectral range of 200 to 600 nm as shown in Fig. 2a. It reveals that the absorbance is at a minimum in the visible region with the wavelength cut-off at ∼304 nm. UV-vis spectral data of FPMI were calculated by TD-DFT/ZINDO/CIS methods and the absorption peak, excitation energy and oscillator strength values are summarized in Table 2. The theoretical spectra of FPMI are shown in Fig. 2b–d. It appears that the ZINDO method is more accurate since it closely resembles the experimental value.

Fig. 2 UV-vis spectra of (a) experimental, (b) ZINDO, (c) TD-DFT and (d) CIS.

Table 2 Theoretical electronic absorption spectral values of FPMI

Method	Wavelength (λmax, nm)	Excitation energies (eV)	Oscillator strengths (f)
ZINDO	304	3.0437	0.7465
TD-DFT	331	3.3198	0.5841
CIS	237	2.3740	0.904

---

3.3. Thermal analysis

In order to test the thermal stability of FPMI the thermogravimetric analysis (TG) and differential thermal analysis (DTA) have been carried out simultaneously. The TG/DTA response curve is shown in Fig. S4.† From the figure it is observed that the TG curve loses 10% of mass due to the removal of water molecules (experimentally observed loss: 3.6%; theoretically expected: 3.5%). In the DTA curve the endothermic peak observed at 115 °C is attributed to melting of the FPMI crystal. In the TG curve the major weight loss is from 300 to 400 °C. It is clearly revealed that the mass of the samples remains unchanged until a temperature of 300 °C and loses its weight almost completely at around 400 °C. This variation in weight loss after 300 °C indicates the decomposition of the sample and it extends up to 400 °C. No exothermic or endothermic peak was observed below the melting point endotherm, indicating the absence of any isomorphic phase transitions in the sample. The sharpness of the endothermic peak shows a good degree of crystallinity of the as-grown material.

3.4. X-ray diffraction analysis

The as-grown FPMI crystal was finely powdered and subjected to powder XRD analysis. The indexed powder XRD pattern of the as-grown FPMI is shown in Fig. 3 along with the simulated one. The XRD profiles show that the sample is of single phase without a detectable impurity. The well defined Bragg peaks at specific 2θ angles show the high crystallinity of the material. Most of the peak positions in the powder and simulated X-ray diffraction patterns from the single crystal XRD analysis coincide but the relative intensities differ. Possibly this could be due to the preferred orientation of the sample used for the diffractogram measurement and the difference in the mosaic spread of the powder and single crystal patterns.

Fig. 3 Simulated and experimental indexed powder XRD patterns of FPMI.

The FPMI crystal belongs to the triclinic system with the centrosymmetric space group P1̄. The ORTEP and packing diagrams are shown in Fig. 4 and the crystal data are given in Table 3.

Fig. 4 (a) ORTEP, (b) optimized molecular structure and (c) packing diagram of FPMI.

Table 3 Crystal data and structure refinement for FPMI

Empirical formula	C19H18 FN3O3
Formula weight	355.36
Temperature	293(2) K
Wavelength	0.71073 Å
Crystal system, space group	Triclinic, P1̄
Unit cell dimensions	a = 8.6739(4) Å, α = 75.1390(10)°
	b = 9.7386(4) Å, β = 74.865(2)°
	c = 11.1516(5) Å, γ = 88.181(2)°
Volume	878.28(7) Å^3
Z, calculated density	2, 1.344 Mg m^−3
Absorption coefficient	0.100 mm^−1
F(000)	372
Crystal size	0.35 × 0.30 × 0.30 mm^3
Theta range for data collection	2.17 to 25.00°
Limiting indices	−10 ≤ h ≤ 10, −11 ≤ k ≤ 11, −13 ≤ l ≤ 13
Reflections collected/unique	15 680/3108 [R(int) = 0.0257]
Completeness to theta = 22.20	99.9%
Absorption correction	Semi-empirical from equivalents
Max. and min. transmission	0.9836 and 0.9536
Refinement method	Full-matrix least-squares on F^2
Data/restraints/parameters	3108/7/266
Goodness-of-fit on F^2	1.058
Final R indices [I > 2 sigma(I)]	R1 = 0.0384, wR2 = 0.1055
R indices (all data)	R1 = 0.0470, wR2 = 0.1124
Extinction coefficient	0.012 (3)
Largest diff. peak and hole	0.179 and −0.131 e Å^−3

---

In the title compound the fluorine atom is disordered over two positions with the site occupancy ratio of 63 : 37. The anisotropic displacement parameters of the disordered atom were restrained with an effective standard deviation of 0.02 Ų. The O1 atom and the hydrazinic N3 atom are cis with respect to the C14–N2 bond. The structure of the compound reveals the quasi coplanarity of the whole molecular skeleton with localization of the double bonds in the central [double bond splayed left]C=N–N–C=O moiety which has an E-configuration with respect to the double bond of the hydrazone bridge. A trans configuration is fixed around the N2–N3 single bond of length 1.3800(16) Å. The central part of the molecule C7–N3–N2–C14–O1, adopts a completely extended conformation. The bond lengths C7–N3 (1.2891(18) Å) and C14–O1 (1.2182(16) Å) are typical of double bonds. In the crystal structure, molecules are linked through intermolecular C–H⋯O, C–H⋯F, O–H⋯O and O–H⋯N hydrogen bonds (Fig. 4c). The hydrogen bond symmetry is listed in Table 4.

Table 4 Hydrogen bonds geometry of FPMI (Å, °)^a

D–H⋯A	d(D–H)	d(H⋯A)	D(D⋯A)	<(DHA)
a Symmetry transformations used to generate equivalent atoms: #1 x, y + 1, z; #2 −x, −y + 2, −z + 3; #3 −x + 1, −y + 1, −z + 2; #4 x, y − 1, z + 1.
C(2)–H(2)⋯O(3)^#1	0.93	2.55	3.413(2)	153.7
C(16)–H(16)⋯F(1)^#2	0.93	2.38	3.173(2)	143.1
O(2)–H(2A)⋯O(3)^#3	0.904(16)	1.921(16)	2.813(2)	169(2)
O(2)–H(2B)⋯O(1)	0.900(16)	2.005(19)	2.8521(17)	156(2)
O(3)–H(3A)⋯N(1)	0.902(16)	2.003(17)	2.8491(19)	156(2)
O(3)–H(3B)⋯O(2)^#4	0.897(16)	1.933(17)	2.7841(18)	158(2)

---

The experimental and calculated data refer to bond length (exp.) and bond length (cal.), respectively. The agreement between the theoretical and experimental results has been expressed by the root mean square deviation (RMSD) using the following expression:

where n is the number of experimental or calculated data. The RMSD of the observed single crystal XRD bond length is found to be of 0.5160% error. This is caused by neglecting anharmonicity and electron correlation.

3.5. First-order molecular hyperpolarizability

The calculated polarizability (α), first-order molecular hyperpolarizability (β) and dipole moment (μ) of the specimen are 37.10 × 10⁻²⁴ esu, 23.458 × 10⁻³⁰ esu (∼84 times that of urea) and 8.4513 D, respectively (Table 5). The maximum value of hyperpolarizability is due to the nonzero μ values. High β is associated with high charge transfer. The β values of some hydrazide derivatives are listed in Table 6. It is interesting to observe that the substitution of fluorine in the para position of the benzophenone ring enhances the hyperpolarizability significantly i.e., ∼16 times that of the unsubstituted hydrazide which is ∼84 times that of urea. But even this significant rise in β could not be translated at the macro level and a negligible second harmonic generation efficiency is observed due to an orientation effect resulting in a centrosymmetric structure. The optimized molecular structure of FPMI (Fig. 4b) closely resembles the displacement ellipsoid diagram (Fig. 4a).

Table 5 The calculated dipole moment (in D), β components (a.u.), β_tot value (in esu), α components (a.u.), α_tot value (in esu) and HOMO–LUMO (eV) characteristic for FPMI

First-order molecular hyperpolarizability
βxxx	2514.006
βxxy	21.951
βxyy	162.925
βyyy	127.131
βxxz	−52.112
βxyz	25.779
βyyz	−31.628
βxzz	33.914
βyxx	−13.582
βzzz	8.221
βtot (×10^−30)	23.458

---

Polarizability
αxx	349.687
αxy	16.8106
αyy	263.897
αxz	11.930
αyz	−5.925
αzz	136.058
αtot (×10^−24)	37.10

---

Dipole moment
μx	−5.192
μy	6.645
μz	−0.556
μ	8.451

---

Frontier molecular orbital
EHOMO	−6.3538
ELUMO	−2.1418
EHOMO − ELUMO	4.2120

---

Table 6 First-order molecular hyperpolarizability (β) values of some hydrazides

Compound	β (×10^−30) esu	Ref.
4-Benzoylpyridine isonicotinyl hydrazone monohydrate	2.799 (∼10 times that of urea)	15
Benzophenone-2-furoyl hydrazone	0.817 (∼2.5 times that of urea)	16
(E)-N′-(Diphenylmethylene)isonicotinohydrazide dihydrate	1.673 (∼5 times that of urea)	17
(E)-N′-((Pyridin-2-yl)methylene)benzohydrazide monohydrate	4.360 (12 times that of urea)	23
N′-(2-Methyl-3-phenylallylidene)nicotinohydrazide	18.380	24
(E)-N′-((4-Fluorophenyl)(phenyl)methylene)isonicotinohydrazide dihydrate	23.458 (∼84 times that of urea)	Present work

---

3.6. Molecular electrostatic potential

The molecular electrostatic potential (MEP) at a point in the space around a molecule gives an indication of the net electrostatic effect produced at that point by the total charge distribution (electron + proton + nucleus) of the atom or molecule and correlates with the dipole moments, electronegativity, partial charges and chemical reactivity of the molecule. The different values of the electrostatic potential at the surface are represented by different colors: red represents regions of most negative electrostatic potential, blue represents regions of most positive electrostatic potential, and green represents regions of zero potential. The order of increase of potential is, red < orange < yellow < green < blue. The electrophiles tend to the negative and the nucleophiles tend to the region of positive MEP (Fig. 5a). In FPMI, the carbonyl group behaves as an electrophilic region and it is denoted as red. Likewise, the nucleophilic region was graphically shown as blue. Molecular surfaces obtained at the B3LYP level with 6-31G(d,p) as the basis set are shown in Fig. 5.

Fig. 5 Molecular surface images of FPMI.

3.7. Mulliken population analysis

In the application of quantum mechanical calculations to molecular systems, the calculation of the effective atomic charge plays an important role. Mulliken atomic charges are calculated by determining the electron population of each atom as defined by the basis function. Fig. 6a and b show the Mulliken atomic charges of FPMI. From the atomic charge values, the oxygen (O26, O37 and O40), nitrogen (N22, N23 and N34), fluorine (F44) and carbon (C1–C5, C12–C17, C28 and C29) atoms in FPMI had a large negative charge and behaved as electron donors. The remaining atoms are acceptors exhibiting positive charges. The negative charges on nitrogen/oxygen/fluorine, which are donor atoms, and the net positive charge on the hydrogen atom, which is an acceptor atom, suggest the presence of intermolecular hydrogen bonding interactions in FPMI. Hydrogen bonding interactions are clearly shown by the packing diagram from single crystal XRD data (Fig. 5c).

Fig. 6 (a) Mulliken atomic charge distribution and (b) Mulliken plot of FPMI.

3.8. Natural bond orbital (NBO) analysis

The NBO analysis examines all possible interactions between filled (donor) Lewis-type NBOs and empty (acceptor) non-Lewis NBOs and estimates their energetic importance by second-order perturbation theory.²⁶ The one-centre lone pairs and two-centre bonds from NBO analysis present an exact representation of chemical bonding for a stable molecular species, corresponding to a single Lewis structure. The non-Lewis set includes unoccupied valence nonbonding (LP*) and extra-valence-shell Rydberg (RY*) orbitals as well as the valence antibonds (BD*). The deficiency of the Lewis-type NBOs (bonds and lone pairs) in representing the density matrix can be quantified with the occupancy of these NBOs. The energy of the delocalization, ΔE_ij is calculated as

E⁽²⁾ = ΔE_ij = q_iF(i,j)²/(ε_j − ε_i)

where E⁽²⁾ is the energy of hyperconjugative interactions, q_i is the occupancy of the donating (Lewis-type) orbital, ε_i and ε_j are the energies of the donating and accepting orbitals, and F_ij is the off-diagonal element of the Fock matrix in the NBO basis.²⁷ NBO analysis has been performed on the FPMI molecule at the B3LYP/6-31G(d,p) level in order to explain the intramolecular hybridization and delocalization of electron density within the molecule. The intramolecular hyperconjugative interactions of the σ(C10–N22) orbital with the σ*(C12–C14) orbital lead to strong stabilization energies of 0.65 kJ mol⁻¹. The most important interaction energy in this molecule is the electron donation from the LP orbital (N23) to the antibonding acceptor π*(C25–O26), resulting in a lower stabilization energy of 51.58 kJ mol⁻¹. The interaction of the same σ(N23) with π*(C25–O26) leads to a moderate stabilization energy of 27.84 kJ mol⁻¹. Interaction of the LP orbital (N23) with the antibonding acceptor σ*(C25–O26) leads to a strong stabilization energy of 1.12 kJ mol⁻¹. The maximum stabilization delocalization takes part in the σ–σ* transition. The E⁽²⁾ values and types of the transition are shown in Table 7.

Table 7 Second order perturbation theory analysis of the Fock matrix in NBO basis set for FPMI

Donor (i)	ED (i)^a/(e)		Acceptor (j)	ED (j)^a/(e)	E^(2)^b/kJ mol	E(j) − E(i)^c/a.u.	F(i,j)^d/a.u.
a ED is the occupation number.b E^(2) is the energy of hyperconjugative interactions.c Energy difference between donor and acceptor i and j NBO orbitals.d F(i,j) is the Fock matrix element between i and j NBO orbitals.
(σ) C10–C11	1.96577	RY*	(σ) C2	0.0048	1.3	1.94	0.045
		BD*	(σ) C12–C13	0.02417	1	1.2	0.031
		BD*	(π) C12–C13	0.3722	0.9	0.66	0.024
		BD*	(σ) N22–N23	0.02204	5.25	1.03	0.066
(σ) C10–C12	1.97447	RY*	(σ) C11	0.0065	2.1	1.84	0.056
		BD*	(σ) C10–N22	0.01772	1.44	1.25	0.038
		BD*	(σ) C13–C15	0.01408	2.35	1.22	0.048
(σ) C10–N22	1.98537	RY*	(σ) C11	0.0065	0.97	2.08	0.04
		BD*	(σ) C12–C14	0.02418	0.65	1.44	0.027
		BD*	(σ) N23–C25	0.07764	2.33	1.34	0.051
(σ) C19–F44	1.99588	RY*	(σ) C19	0.00924	0.85	1.84	0.035
		BD*	(σ) C13–C15	0.01408	1.33	1.59	0.041
		BD*	(σ) C14–C17	0.014	1.32	1.59	0.041
(σ) N22–N23	1.98544	RY*	(π) C10	0.00514	1.04	1.8	0.039
		BD*	(σ) C10–C11	0.03727	3.28	1.33	0.059
		BD*	(σ) C10–N22	0.01772	0.57	1.45	0.026
(σ) N23–H24	1.9876	RY*	(σ) N22	0.00669	0.97	1.61	0.035
		BD*	(σ) C25–O26	0.01949	3.67	1.27	0.061
		BD*	(π) C25–O26	0.29574	0.54	0.72	0.019
(σ) N23–C25	1.98887	RY*	(σ) N22	0.00669	1.44	1.75	0.045
		BD*	(σ) C10–N22	0.01772	2.11	1.42	0.049
		BD*	(σ) N22–N23	0.02204	0.69	1.21	0.026
		BD*	(σ) N23–H24	0.04055	0.59	1.26	0.025
		BD*	(σ) C25–O26	0.01949	0.76	1.41	0.029
		BD*	(σ) C27–C29	0.0209	1.28	1.4	0.038
(σ) C25–O26	1.99438	RY*	(σ) C25	0.01648	1.31	1.86	0.044
		BD*	(σ) N23–C25	0.07764	0.75	1.48	0.03
(σ) C30–N34	1.98754	RY*	(π) C28	0.00211	1.19	1.59	0.039
		BD*	(σ) C30–H35	0.01943	0.54	1.3	0.024
		BD*	(σ) C32–N34	0.01615	1.18	1.36	0.036
		BD*	(σ) C32–H36	0.02165	1.95	1.33	0.046
(σ) C32–N34	1.98689	RY*	(π) C29	0.00257	1.44	1.65	0.044
		BD*	(σ) C30–N34	0.01686	1.2	1.36	0.036
		BD*	(σ) C30–H35	0.01943	2.39	1.29	0.05
(σ) N22	−1.99928	BD*	(σ) C10–C11	0.03727	0.52	14.66	0.079
		BD*	(σ) C10–C12	0.04447	0.96	14.63	0.107
		BD*	(σ) N23–H24	0.04055	0.64	14.62	0.087
		BD*	(σ) N23–C25	0.07764	0.64	14.64	0.088
(σ) O26	−1.99975	RY*	(σ) C25	0.01648	5.7	19.7	0.3
		BD*	(σ) N23–C25	0.07764	0.59	19.32	0.097
(σ) F44	−1.99994	RY*	(σ) C19	0.00924	2.53	25.27	0.226
(σ) N23	1.64853	BD*	(π) C10–N22	0.20304	27.84	0.29	0.084
		BD*	(σ) C25–O26	0.01949	1.12	0.85	0.03
		BD*	(π) C25–O26	0.29574	51.58	0.3	0.113
(π) O26	1.85975	BD*	(σ) N23–C25	0.07764	28.12	0.7	0.127
		BD*	(σ) C25–C27	0.06747	17.44	0.67	0.098
(π) C32–N34	0.37342	BD*	(π) C27–C29	0.32643	155.83	0.02	0.088
		BD*	(π) C28–C30	0.30186	205.07	0.01	0.079
(π) C10–N22	0.20304	BD*	(π) C3–C11	0.37837	75.23	0.02	0.066
(π) C32–N34	1.70795	BD*	(π) C27–C29	0.32643	13.78	0.33	0.06
		BD*	(π) C28–C30	0.30186	26.96	0.32	0.083
(π) C28–C30	1.64346	BD*	(π) C27–C29	0.32643	21.06	0.29	0.071
		BD*	(π) C32–N34	0.37342	16.58	0.27	0.06

---

3.9. Hirshfeld surfaces analysis

The Hirshfeld surfaces of FPMI have been demonstrated in Fig. 7, showing surfaces that have been mapped over d_norm, shapeindex, curvedness, d_e and d_i. The Hirshfeld surface^28–30 surrounding a molecule is defined by the points where the contribution to the electron density from the molecule under contribution is equal to the contribution from all the other molecules. For each point on that isosurface two distances are determined: one is d_e representing the distance from the point to the nearest nucleus external to the surface, and the second is d_i representing the distance to the nearest nucleus internal to the surface. The normalized contact distance (d_norm) is based on both d_e and d_i. The surfaces are shown as transparent to allow visualization of the molecule around which they were calculated. Hydrogen bonding contacts are revealed by circular depressions (deep red) visible on the Hirshfeld surface, and the other visible spots are due to hydrogen bonding interactions: O⋯H (8.2%), H⋯O (7.1%), H⋯F (5.0%), F⋯H (4.6%) and F⋯F (2.1%) contacts (Fig. 7a) and O⋯H (8.2%), H⋯O (7.1%), H⋯F (5.0%), F⋯H (4.6%) and F⋯F (2.1%) interactions (Fig. 7b). The deep red coloured spots in d_e (Fig. 7c) are strong interactions such as O⋯H (8.2%). The dominant interactions are H⋯O (7.1%) and H⋯F (5.0%), which can be seen in the d_i surface plots as the bright red area in Fig. 7d. Hirshfeld surfaces of individual molecules are given in Fig. 7 for a better understanding of the molecular interactions. The red spots on the surface indicate close contacts. The shapeindex indicates the shape of the electron density surface around the molecular interactions. The small range of area and the light color on the surface represent weaker and longer contacts other than hydrogen bonds. The curvedness surface indicates the electron density surface curves around the molecular interactions. Three dimensional images of the crystal packing along the a-axis, b-axis and c-axis are shown in Fig. 8–10. The deformation density, the difference between the total electron density of a molecule and the electron density of “neutral spherical unperturbed atoms” superimposed at the same atomic positions of the molecule, is calculated as 0.008 (maximum) and −0.008 (minimum) a.u. (a.u. is atomic units). A graphical view of the deformation density is shown in Fig. 11.

Fig. 7 Hirshfeld surface analysis of FPMI (a) d_norm (front view) (b) d_norm (back view) (c) d_e (d) d_i (e) curvedness (f) shapeindex.

Fig. 8 Crystal packing showing hydrogen bonding interactions along the ‘a’ axis.

Fig. 9 Crystal packing showing hydrogen bonding interactions along the ‘b’ axis.

Fig. 10 Crystal packing showing hydrogen bonding interactions along the ‘c’ axis.

Fig. 11 Deformation density surface of FPMI.

3.10. Fingerprint analysis

The two-dimensional fingerprint plots³⁰ of FPMI exemplify the strong evidence for the intermolecular interactions pattern. In the fingerprint plots (Fig. 12), O⋯H (8.2%) interactions are represented by a spike at the bottom of the plot whereas the H⋯O (7.1%) interactions are represented by a spike in the top left region. Hydrogen bonding interactions H⋯H (40.4%) are very high when compared to the other bonding interactions. The sharp curved spike at the bottom left area indicates the H⋯F (5.0%) interaction and the top left corner with the curved spike indicates the F⋯H (4.6%) interaction. The fingerprint at the top left area represents H⋯C (7.2%) interactions and the top right area represents C⋯H (9.6%) interactions. The fingerprint at the bottom right area represents N⋯H (2.3%) interactions and the top left area represents H⋯N (1.8%) interactions. The sharp curved spike at the centre area indicates the F⋯F (2.1%) interactions. The combination of d_e and d_i in the form of a two-dimensional fingerprint plot provides a summary of the intermolecular contacts in the crystal. The numbers of interactions in terms of percentages are represented in a pie chart (Fig. 13).

Fig. 12 Fingerprint plots of FPMI.

Fig. 13 Relative contribution of the various intermolecular interactions in FPMI.

4. Conclusions

Single crystals of (E)-N′-((4-fluorophenyl)(phenyl)methylene)isonicotinohydrazide dihydrate were successfully synthesized and grown by the slow evaporation solution growth method at room temperature. The grown crystals have been subjected to various characterization studies. The functional groups of the grown compound have been identified by FT-IR and FT-Raman analyses. The total molecular weight was confirmed by mass spectral analysis. The number of protons and carbons present in the compound were confirmed by NMR analysis. The crystallographic data indicate that the FPMI crystallizes in the triclinic system with the centrosymmetric space group P1̄ while the precursor benzophenone belongs to the orthorhombic system with the noncentrosymmetric space group P2₁2₁2₁. The minimum absorption in the visible region is observed from the UV-vis measurement. This is an important requirement for materials having NLO properties. Optimized geometrical parameters are close to the experimental values. Molecular stability was successfully analysed using NBO second order Fock matrix analysis. Electron delocalization is confirmed by MEP, ESP, total density and alpha density maps. The intermolecular charge transfer is evidenced by Mulliken charge population analysis. High first-order molecular hyperpolarizability associated with high charge transfer clearly reveals the molecular level nonlinearity. The analysis of Hirshfeld surface derived fingerprint plots is an effective method to identify the different types of intermolecular interactions. Further work is in progress to design a noncentrosymmetric structure so that nonlinearity at the macrolevel can be achieved.

Acknowledgements

The authors thank SAIF, IIT Madras, Chennai for providing single crystal XRD facility. The authors thank the Council of Scientific and Industrial Research (CSIR), New Delhi, for financial support through research grant No. 03(1233)/12/EMR-II, and VM is grateful to CSIR project for the award of SRF (Extended).

References

1. C. Loncle, J. M. Brunel, N. Vidal, M. Dherbomez and Y. Letourneux, Eur. J. Med. Chem., 2004, 39, 1067–1071.
2. S. Papakonstantinou-Garoufalias, N. Pouli, P. Markos and A. Chytyroglou-Ladas, Il Farmaco, 2002, 57, 973–977.
3. P. Vicini, F. Zani, P. Cozzini and I. Doytchinova, Eur. J. Med. Chem., 2002, 37, 553–564.
4. B. K. Kaymakcroglu and S. Rollas, Il Farmaco, 2002, 57, 595–599.
5. R. Maccari, R. Ottana and M. G. Vigorita, Bioorg. Med. Chem. Lett., 2005, 15, 2509–2513.
6. M. T. Cocco, C. Congiu, V. Onnis, M. C. Pusceddu, M. L. Schivo and A. Logu, Eur. J. Med. Chem., 1999, 34, 1071–1076.
7. D. G. Rando, D. N. Sato, L. Siqueira, A. Malvezzi, C. Q. F. Leite, A. T. Amaral, E. I. Ferreira and L. C. Tavares, Bioorg. Med. Chem., 2002, 10, 557–560.
8. J. Patole, D. Shingnapurkar, S. Padhye and C. Ratledge, Bioorg. Med. Chem. Lett., 2006, 16, 1514–1517.
9. A. Maiti and S. Ghosh, J. Inorg. Biochem., 1989, 36, 131–139.
10. D. Sriram, P. Yogeeswari and K. Madhu, Bioorg. Med. Chem. Lett., 2005, 15, 4502–4505.
11. N. Mori, US patent No. 5, 567, 557, 1996.
12. N. Tatsya and U. Minoru, Japan Patent No. 8, 101, 524, 1996.
13. Y. Suzuki, US Patent No. 5, 6656, 500, 1997.
14. N. Jurban, Z. Tokarski and T. P. Smith, US Patent No. 6, 340, 548, 2002.
15. V. Meenatchi, K. Muthu, M. Rajasekar and SP. Meenakshisundaram, Spectrochim. Acta, Part A, 2014, 124, 423–428.
16. V. Meenatchi, K. Muthu, M. Rajasekar and SP. Meenakshisundaram, Optik, 2014, 125, 4196–4200.
17. V. Meenatchi, K. Muthu, M. Rajasekar, G. Bhagavannarayana and SP. Meenakshisundaram, Optik, 2014, 125, 4181–4185.
18. M. J. Frisch and G. W. Trucks, et al., Gaussian09, Revision C.01, Gaussian, Inc., Wallingford, CT, 2009.
19. R. Dennington, T. Keith and J. Millam, GaussView, Version 5, Semichem Inc., Shawnee Mission KS, 2009.
20. B. Schlegel, J. Comput. Chem., 1982, 3, 214–218.
21. R. M. Silverstein, F. X. Webster and D. J. Kiemle, Spectroscopic identification of organic compounds, John Wiley & Sons, 7th edn, 2005.
22. S. Sylvestre and K. Pandiarajan, Spectrochim. Acta, Part A, 2011, 78, 153–159.
23. N. Ramesh Babu, S. Subashchandrabose, M. Syed Ali Padusha, H. Saleem, V. Manivannan and Y. Erdogdu, J. Mol. Struct., 2014, 1072, 84–93.
24. A. Manimekalai, N. Saradhadevi and A. Thiruvalluvar, Spectrochim. Acta, Part A, 2010, 77, 687–695.
25. P. Kubelka and F. Munk, Zeitschrift fur technische Physik, 1931, 12, 593–601.
26. E. D. Glendening, J. K. Badenhoop, A. D. Reed, J. E. Carpenter and F. Weinhold, NBO 3.1, Theoretical Chemistry Institute, University of Wisconsin, Madison, WI, 1996.
27. J. J. Dannenberg, Chem. Rev., 1999, 99, 1225–1241.
28. F. L. Hirshfeld, Theor. Chim. Acta, 1977, 44, 129–138.
29. S. K. Wolff, D. J. Grimwood, J. J. McKinnon, M. J. Turner, D. Jayatilaka and M. A. Spackman, CrystalExplorer (Version 3.1), University of Western Australia, 2012.
30. M. A. Spackman and J. J. McKinnon, CrystEngComm, 2002, 4, 378–392.

---

Footnote

† Electronic supplementary information (ESI) available: Characterization techniques (methodology), FT-IR vibrational modes (experimental and theoretical), FT-Raman, band gap energy and thermal analyses. CCDC 947423. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ra08454g

---