J. Sampath and P. Kathiravanjoics.org/gallery/ics-1772.pdfE – Mail address: [email protected] (T. Balakrishnan) 1. Introduction Dopamine, 3,4-dihydroxyphenylethylamine

HF and DFT calculations of Crystal Growth and Characterization of

Dopaminium nitrate, [2 - (3, 4 – Dihydroxyphenyl) ethanaminium nitrate]

C8H12NO2+.NO3

- single crystal

J. Sampatha* and P. Kathiravanb,

aAssistant Professor, Department of Physics, Annapoorana Engineering College, Salem-636

308,India

bCrystal Growth Laboratory, PG & Research Department of Physics, Annai Arts and Science

College, Harur-636903 Tamil Nadu, India.

Abstract

An effective organic nonlinear optical single crystal, dopaminium nitrate (DN), was

grown by slow evaporation solution growth technique at room temperature. The cell parameters

of grown single crystal were estimated by single crystal X – ray diffraction analysis. The

optimized geometrical parameters of dopaminium nitrate was obtained from ab initio HF and

DFT calculations. The computed geometrical parameters are in good agreement with the

observed X-ray diffraction data. The HOMO and LUMO energy gap explains the eventual

charge transfer interactions taking place within the molecule. Furthermore, the molecular

electrostatic potential (MEP) map, Mulliken atomic charges and thermodynamic properties of

DN were calculated and the results are discussed.

Keywords: Crystal growth, X – ray Diffraction, UV – Vis – NIR spectrum, Thermal analysis,

Antimicrobial activity

*Corresponding author Tel: +91 – 9443445535

E – Mail address: [email protected] (T. Balakrishnan)

1. Introduction

Dopamine, 3,4-dihydroxyphenylethylamine or 3-hydroxytyramine, one of the most

intense and dynamic areas of research in behavioral neuroscience is the study of the functions of

brain dopamine (DA) [1] DA has been implicated in several disorders, including schizophrenia,

depression and Parkinson’s disease. Moreover, the dominant paradigm in drug abuse research

has been, for the past several years, the hypothesis that DA is the critical neurotransmitter for the

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mailto:[email protected]

mediation of reinforcement phenomena [2]. The function of the dopamine (DA) transporter

(DAT) is to recycle DA following its neuronal release. In this way it regulates the extracellular

lifetime of this neurotransmitter. Interference with normal DA transport by drugs of abuse such

as amphetamine and cocaine [3-4] results in significant behavioral changes in animals.

Molecular cloning of the DAT, as well as other amine transporters, has permitted the

biochemical and pharmacological properties of these transporters to be examined in cultured

cells in detail [5] and without the interference of cytoplasmic amine clearance by the vesicular

monoamine transporter [6]. Dopamine is an important regulator of many physiological functions,

including control of locomotion, cognition, and neuroendocrine hormone secretion. The neural

transporter also plays major role in calibrating the duration and intensity of dopamine

neurotransmission in the central nervous system [7]. Sofian Gatfaoui et al., [8] have reported the

single crystal structure of Dopaminium nitrate and it belongs to triclinic system with the space

group P1. In the present study we report the DA single crystal growth from aqueous solution by

slow evaporation at room temperature.

2. Experimental

2.1 Synthesis

The AR grade dopamine hydrochloride and nitric acid were mixed in equimolar ratio in

double distilled water. The purity of the synthesized salt was further increased by repeated

recrystallization. The reaction mechanism of synthesis of dopaminium nitrate (DN) is depicted in

scheme 1.

OH

Dopaminehydrochloride + HNO3

OH

NH2

+ HNO3

OH

OH

NH+

3

+NO-3

Dopaminium nitrate

HClHCl

Scheme 1. The reaction mechanism of DN single crystal

2.2 Crystal Growth

The purified crystalline salt of DN was dissolved in double distilled water at room

temperature. The obtained solution was stirred for 30 min and then filtered using Whatman filter



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paper. The filtered solution was placed in a beaker covered with perforated polythene sheet and

placed in a dust free atmosphere for slow evaporation of solvent at room temperature. The good

quality single crystals of DN were harvested in about the growth period of 11 days. The size of

the grown DN crystal is about 5 × 3 × 3 mm3 (Fig.1.).

Fig. 1. As grown DN single crystals

3. Result and Discussion

3.1 X – ray diffraction study

One of the grown single crystals was subjected to single crystal X – ray diffraction

analysis at room temperature using ENRAF – NONIUS CAD 4 diffractometer with MoKα

radiation source (λ = 0.71073Å).

0 10 20 30 40 50 60 70 80 90

-1000

0

1000

2000

3000

4000

5000

6000

7000

11

0

01

1

-11

10

02

10

1-1

01

11

1

11

0

00

1

01

0

-11

00

12

12

00

21

-10

21

20

10

2

Inte

nsi

ty (

arb

.un

it)

2(degree)

11

2



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Fig. 2. Powder XRD pattern of DN.

The lattice parameters of DN crystals obtained are compared with the values reported by Sofian

Gatfaoui et al., [8] in Table 1. The powder X-ray diffraction study was carried using RICH

SEIFERT with Cu Kα (λ = 1.5406 Å) radiation in the 2θ range of 10 – 80◦ with a scan rate of 2

◦/min. Figure 2 shows the powder XRD pattern of DN and all the observed reflection peaks were

indexed using the software AUTOX 93.

Table 1. Single crystal X – ray diffraction data for grown DN crystals

Cell Parameters Present study Reported [8]

a 8.452 Å 8.3066 Å

b 10.56 Å 10.4856 Å

c 11.35 Å 11.2303 Å

α 80.16˚ 79.623˚

β 89.69˚ 89.868˚

γ 82.93˚ 82.357˚

Crystal system Triclinic Triclinic

3.2 Molecular geometry

In order to provide information with regard to the structural characteristics of

dopaminium nitrate, the Hartree–Fock and DFT-B3LYP correlation functional calculations were

carried out. The entire calculations were performed using the GAUSSIAN 09W software

package [9]. Initially, the HF level calculations, adopting the 6-311++G(d,p) basis set were

carried out and then the DFT employing the Becke 3LYP keyword, which invokes Becke’s

three-parameter hybrid method [10] was computed using the correlation function of Lee et al.

[11], implemented with 6-311++G(d,p) basis set. The molecular structure of dopaminium nitrate

is shown in Fig. 3. The optimization geometrical parameters of DN obtained by the ab initio HF

and DFT/B3LYP with 6-311++G(d,p) as basis set are listed in Table 2. The benzene ring appears

little distorted and angles slightly out of perfect hexagonal structure. It is due to the substitutions

of the –CH2-CH2-NH3+, NO3

- and hydroxyl groups. The structural data provided in Table 2

indicates that various bond lengths are found to be almost same at HF/6-311++G(d,p) and

B3LYP/6-311++G(d,p) levels. However, the B3LYP/6-311++G(d,p) level of theory, in general

slightly over estimates bond lengths but it yields bond angles in excellent agreement with the HF

method. The calculated geometrical parameters were compared with X-ray diffraction results



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[12]. The corresponding experimental and calculated geometric parameters agree well with each

other. The small deviations are probably due to the intermolecular interactions in the crystalline

state of the molecule and also due to that the theoretical calculations belong to isolated molecule

in gaseous phase while the experimental results belong to molecule in solid state. The calculated

geometrical parameters represent a good approximation and they are the bases for calculating

several thermodynamics parameters.



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Fig. 3. Molecular model of dopaminium nitrate along with numbering of atoms.

Table 2

Optimized geometrical parameters for dopaminium nitrate computed at HF and B3LYP methods with 6-311++G(d,p) basis set.

Bond

Length

Value (Å) Bond angle Value (o)

6-311++G(d,p) Expta 6-311++G(d,p) Expta

HF B3LYP HF B3LYP

R(1,2) 1.3943 1.4051 1.395 A(2,1,6) 119.5676 119.5832 119.46

R(1,6) 1.3811 1.391 1.385 A(2,1,10) 120.4129 120.0937 116.37



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R(1,10) 1.3447 1.3589 1.3674 A(6,1,10) 120.0186 120.3195 124.11

R(2,3) 1.3787 1.3893 1.3899 A(1,2,3) 119.7928 119.7505 119.73

R(2,11) 1.3513 1.3639 1.3738 A(1,2,11) 116.6061 116.1017 121.11

R(3,4) 1.3934 1.4012 1.389 A(3,2,11) 123.601 124.1473 119.15

R(3,7) 1.074 1.0838 0.93 A(2,3,4) 120.9957 120.9841 121.22

R(4,5) 1.3863 1.3979 1.395 A(2,3,7) 118.6725 118.8875 119.4

R(4,14) 1.5147 1.5146 1.5166 A(4,3,7) 120.3257 120.1252 119.4

R(5,6) 1.3885 1.3961 1.391 A(3,4,5) 118.7105 118.7076 118.26

R(5,8) 1.0769 1.0855 0.93 A(3,4,14) 119.236 118.9457 120.03

R(6,9) 1.0743 1.0835 0.93 A(5,4,14) 121.9607 122.2476 121.71

R(10,12) 0.9508 0.9684 0.89 A(4,5,6) 120.514 120.5763 120.29

R(11,13) 0.9576 0.9775 0.86 A(4,5,8) 120.355 120.2601 119.5

R(14,15) 1.0842 1.0931 0.97 A(6,5,8) 119.1297 119.1605 119.5

R(14,16) 1.0852 1.0942 0.97 A(1,6,5) 120.3309 120.2905 120.03

R(14,17) 1.5333 1.5393 1.497 A(1,6,9) 118.5854 118.6231 119.9

R(17,18) 1.0815 1.0916 0.97 A(5,6,9) 121.0745 121.0784 119.9

R(17,19) 1.0813 1.0919 0.97 A(1,10,12) 108.7774 107.5574 109.1

R(17,20) 1.4894 1.4994 1.4856 A(2,11,13) 110.8596 110.3256 111.0

R(20,21) 1.0368 1.0935 0.94 A(4,14,15) 109.9718 109.7302 109.3

R(20,22) 1.007 1.0193 0.90 A(4,14,16) 111.18 111.1913 109.3

R(20,27) 1.0109 1.0251 0.88 A(4,14,17) 112.8442 113.079 111.68

R(23,24) 1.2113 1.2404 1.2522 A(15,14,16) 106.981 106.8933 107.9



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R(23,25) 1.2423 1.2881 1.2596 A(15,14,17) 108.8958 108.9694 109.3

R(23,26) 1.2206 1.2464 1.2448 A(16,14,17) 106.7429 106.7448 109.3

A(14,17,18) 111.2267 111.0744 109.0

A(14,17,19) 111.1482 110.7942 109.0

A(14,17,20) 111.3386 111.6917 112.95

A(18,17,19) 108.7617 108.5416 107.8

A(18,17,20) 107.2079 107.3674 109.0

A(19,17,20) 106.9706 107.2016 109.0

A(17,20,21) 114.549 115.5764 113.2

A(17,20,22) 112.5828 112.0828 113.0

A(17,20,27) 112.3318 111.359 111.3

A(21,20,22) 107.2579 107.5801 110.9

A(21,20,27) 102.5394 102.4343 102.2

A(22,20,27) 106.813 107.0739 105.6

A(24,23,25) 119.7071 119.0018 119.63

A(24,23,26) 121.446 122.263 120.87

A(25,23,26) 118.8039 118.6864 119.5

aExperimental values are taken from Ref. [9].



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3.3 Thermodynamic properties

The values of some thermodynamic parameters (such as zero point vibrational energy,

thermal energy, specific heat capacity, rotational constants, entropy, and dipole moment) of DN

calculated by DFT/B3LYP with 6-311++G(d,p) basis set are listed in Table 3. The global

minimum energy obtained for structure optimization of DN is -797.82995653 Hartrees. Dipole

moment reflects the molecular charge distribution and is given as a vector in three dimensions.

Therefore, it can be used as descriptor to depict the charge movement across the molecule.

Direction of the dipole moment vector in a molecule depends on the centers of positive and

negative charges. Dipole moments are strictly determined for neutral molecules. For charged

systems, its value depends on the choice of origin and molecular orientation. In the present study,

the total dipole moment of DN determined by B3LYP method is 8.8507 Debye. The variation in

zero-point vibrational energies (ZPVEs) seems to be significant. The total energy and the change

in the total entropy of DN at room temperature are also presented. On the basis of vibrational

analysis at B3LYP/6-311++G(d,p) level, the standard statistical thermodynamic functions: heat

capacity (C), entropy (S), and enthalpy changes (∆H), for DN were obtained and are listed in

Table 4. From Table 4, it can be observed that these thermodynamic functions are increasing

with temperature ranging from 100 to 1000 K due to the fact that the molecular vibrational

intensities increase with temperature [13]. All the thermodynamic data supply helpful

information for the further study on the DN. They can be used to compute the other

thermodynamic energies according to relationships of thermodynamic functions and estimate

directions of chemical reactions according to the second law of thermodynamics in

thermochemical field [14].

Table 3 The thermodynamic parameters of dopaminium nitrate calculated by the DFT/B3LYP

method.

Parameters

Method/Basis set

B3LYP/6-311++G(d,p)

Optimized global minimum energy,(Hartrees) -797.82995653

Total energy(thermal), Etotal (kcal mol-1) 142.708

Heat capacity, Cv (kcal mol-1 k-1) 0.0540

Entropy, S (kcal mol-1 k-1)



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Total 0.1205

Translational 0.0420

Rotational 0.0322

Vibrational 0.0463

Vibrational energy, Evib (kcal mol-1)

Zero point vibrational energy, (kcal mol-1) 133.655

Rotational constants (GHz)

A 0.71728

B 0.52823

C 0.34877

Dipole moment (Debye)

μx 2.6533

μy -8.2428

μz -1.8306

μtotal 8.8507

Table 4 Thermodynamic properties at different temperatures at the B3LYP/6-311++G(d,p) level

for dopaminium nitrate.

T (K) S (J/mol.K) C (J/mol.K) ∆H (kJ/mol)

100.00 334.6 107.87 6.93

200.00 429.9 175.03 21.06

298.15 512.34 242.18 41.54

300.00 513.84 243.42 41.99

400.00 592.74 306.7 69.57

500.00 667.09 359.86 102.99

600.00 736.64 402.85 141.2

700.00 801.44 437.58 183.28

800.00 861.79 466.03 228.51



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900.00 918.09 489.66 276.33

1000.00 970.73 509.52 326.32

3.4 HOMO, LUMO analysis

Fig. 4 The atomic orbital compositions of the frontier molecular orbital for dopaminium nitrate.

The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular

orbital (LUMO) are very important parameters for quantum chemistry. The LUMO as an

electron acceptor (EA) represents the ability to obtain an electron and HOMO represents ability



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to donate an electron (ED). The electron transfer from ED groups to the efficient EA groups take

place through -conjugated path [15]. In the present study, the HOMO is located over hydroxyl

groups and the benzene ring; by contrast, the LUMO is delocalized over the –CH2-CH2-NH3+

and NO3- groups; consequently the HOMO→LUMO transition implies an electron density

transfer to –CH2-CH2-NH3+ and NO3

- groups from hydroxyl groups. Moreover, these orbitals

significantly overlap in the para position of the benzene ring for DN. The atomic orbital

compositions of the frontier molecular orbital along with HOMO–LUMO energy gap calculated

at B3LYP/6-311++G(d,p) are shown in Fig. 4. The lowering of HOMO–LUMO energy gap

explains the eventual charge transfer interaction within the molecule, which influences the

biological activity of the molecule.

3.5 Electrostatic potential, total electron density and molecular electrostatic potential

The electrostatic potential was used primarily for predicting sites and relative reactivities

towards electrophilic attack, and in studies of biological recognition and hydrogen bonding

interactions [16]. To predict reactive sites for electrophilic and nucleophilic attack for the

investigated molecule, the MEP at the B3LYP/6-311++G(d,p) optimized geometry was

calculated. In the present study, the electrostatic potential (ESP), electron density (ED) and the

molecular electrostatic potential (MEP) map figures for DN are shown in Fig. 5. The ED plots

for the title molecule show a uniform distribution. However, it can be seen from the ESP figures,

that while the negative ESP is localized more over the O-H groups and NO3- group and is

reflected as a yellowish blob, the positive ESP is localized on the rest of the molecule. This result

is expected, because ESP correlates with electro negativity and partial charges. The negative (red

and yellow) regions of the MEP are related to electrophilic reactivity and the positive (blue)

regions to nucleophilic reactivity, as shown in Fig. 5. As can be seen from the figure, the MEP

map shows that the negative potential sites are on electronegative oxygen atoms of hydroxyl

groups and NO3- group and the positive potential sites are around the hydrogen atoms of the

molecule. The different values of the electrostatic potential at the surface are represented by

different colours. Potential increases in the order red < orange < yellow < green < blue. The color

code of these maps is in the range between -0.09032 a.u. (deepest red) to 0.0932 a.u. (deepest

blue), where blue indicates the strongest attraction and red indicates the strongest repulsion.



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From these results, one can say that the H atoms indicate the strongest attraction and O and N

atoms indicates the strongest repulsion. These sites give information about the region from where

the compound can have intermolecular interactions. Thus, it would be predicted that the DN

molecule will be the most reactive site for both electrophilic and nucleophilic attack and this was

also in support with the literature [17].

Fig. 5 (a) Electrostatic potential (ESP); (b) electron density (ED) and (c) the molecular

electrostatic potential (MEP) map for dopaminium nitrate calculated at B3LYP/6-311++G(d,p)

level.



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3.6 Mulliken atomic charges

Mulliken atomic charge calculation [18] has an important role in the application of

quantum chemical calculation to molecular system, because atomic charges affect dipole

moment, polarizability, electronic structure, and much more properties of molecular systems.

The Mulliken atomic charges of DN obtained by DFT (B3LYP) with 6-311++G (d, p) basis set

are plotted in Fig. 6. The negative values on C1, C2 and C5 atom in the aromatic ring lead to a

redistribution of electron density. Due to this strong negative charges, C3, C4 and C6

accommodate higher positive charge and the molecule becomes more acidic. In the present

molecule, all the hydrogen atoms have a net positive charge; in particular, the hydrogen atom

H12 and H13 have charge of 0.289 and 0.314 respectively, owing to bound with more

electronegativity atom of oxygen.

Fig. 6 Mulliken population analysis chart of dopaminium nitrate.

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Documents

J. Sampath and P. Kathiravanjoics.org/gallery/ics-1772.pdfE – Mail address: [email protected] (T. Balakrishnan) 1. Introduction Dopamine, 3,4-dihydroxyphenylethylamine