Journal of Chemical, Biological and Physical Sciences Structures ...

JCBPS; Section A; February 2018 – April 2018, Vol. 8, No. 2; 171-185.

E- ISSN: 2249 –1929

[DOI: 10.24214/jcbps.A.8.2.17185.]

Journal of Chemical, Biological and Physical Sciences An International Peer Review E-3 Journal of Sciences Available online atwww.jcbsc.org Section A: Chemical Sciences

CODEN (USA): JCBPAT

Research Article

Structures effects of two azo dyes associated with their antimicrobial activities Hanan M. Ali1, Hasanain A S. A Majeed1, Ihsan A. Mkashaf Al-Asadi1, Amel Salih Abdulredha2, Ala`a A. Hussain1 1

Department of Chemistry, College of Education for Pure Sciences, University of Basrah Iraq 2

Department of Biology, College of Education for Pure Sciences, University of Basrah, Iraq Received: 06 March 2018; Revised: 16 March 2018; Accepted: 24 March 2018

Abstract: Antimicrobial activity of two azo dyes, that contain 2-pyrimidinyl and 5-methyl-3-isoxazolyl were carried out against two bacterial species; Staphylococcus aureus (NCTC 6571), Escherichia coli (ATCC 25922) and fungus Candida albicans, using Agar-well diffusion method. The results were showed that the minimum concentration of each azo dye was inhibited Candida albicans and Staphylococcus aureus reasonably. But, the Escherichia coli were resistant against azo dye containing 2-pyrimidinyl. Theoretical studies were approved the structures of azo dyes and their fold a way same to that presents in biomolecules, and showed that the staggered and the eclipsed conformations are interconverted by the rotation about the C-C single bond with an energy variance. Therefore, the conformational analysis of each azo dye is affecting their internal coordinate mechanics (ICM). Add to which, the molecular mechanics (MM2) and molecular mechanics force field (MMFF94) were displayed that the molecular structures of the synthetic azo dyes are affecting their properties, binding and antimicrobial activities. Finally, the MM2 minimization was achieved efficiently with azo dye containing 2pyrimidinyl better than that contain 5-methyl-3-isoxazolyl; the later had high steric effect. But, the MMFF94 minimization and MMFF94 minimization/ sampling of each azo dye were attended successfully. 171

J. Chem. Bio. Phy. Sci. Sec. A, February 2018 – April 2018, Vol. 8, No. 2; 171-185; DOI:10.24214/jcbps.A.8.2.17185.]

Structures …

Hanan M. Ali et al.

Keywords: Antimicrobial activity, Azo dyes, Maximum deviation, Conformational Analysis, Internal Coordinates Mechanics, Molecular Mechanics INTRODUCTION Azo compounds were received high attention in scientific research1, and they have great importance in chemical analysis. Azo compounds contain one or more azo groups (–N=N–) which are linked to SP2 hybridized carbon atoms, based on the number of such groups2. A strongly coloured compounds extremely importance as dyes and also as pigments for a long time3. The 4-acet aminophenol-[2-(4azo)]-N-2-pyrimidinyl-benzene sulfonamide (1)4 and 4-acetamino phenol -[2-(4-azo)]-N-(5-methyl-3isoxazolyl benzene sulfonamide (2)4 were prepared as a new azo dyes using Fox method5. These azo dyes were identified by IR, UV-visible and elemental analysis (CHN)4 The optimized structures of (1) and (2) were obtained by molecular mechanics (MM+), followed by further geometry optimization by the semi-empirical molecular orbital theory at the level of AM14. Internal coordinates are an attractive alternative to the Cartesian coordinates of each atom when particular degrees of freedom are not of interest6. Internal coordinates such as bond lengths, bond angles, and torsion angles are natural coordinates for describing a bonded molecular system7. It has recently been suggested by Mu et al. [Proteins 58, 45 2005)] to use backbone dihedral angles instead of Cartesian coordinates in a principal component analysis of molecular dynamics simulations. Dihedral angles may be advantageous because internal coordinates naturally provide a correct separation of internal and overall motion, which was found to be essential for the construction and interpretation of the free energy landscape of a biomolecule undergoing large structural rearrangements8. Which describe the essential physics of a biomolecular process such as protein folding or molecular recognition9. Internal coordinate also has some advantages for suggesting a new derivatives10. Molecular modeling can be considered as a range of computerized techniques based on theoretical chemistry methods and experimental data that can be used either to analyse molecules and molecular systems or to predict molecular, chemical, and biochemical properties11. One of the major advantages of molecular mechanics compared to other computational techniques is the relative ease with which structures can be optimized via minimization of the corresponding potential energy functions 12. The area of molecular mechanics is to study the detailed structure and physical properties of molecules. Molecular mechanics calculates the energy of a molecule and then adjusts the energy through changes in the bond lengths and angles to obtain the minimum energy structure. More recently, it was recognized that to fully define molecular stereochemistry, one must also take into account change in the spatial arrangements of atoms that occur by low-energy processes involving rotations about single bonds, namely, changes in conformation13. Conformation structure is thus concerned with rotation about single bonds that alter the position of atoms in three dimensions to yield distinguishable stereoisomers called conformations13. Conformation analysis is a relatively new field of study with organic chemistry. Prediction of the energetics associated with conformational changes emerged in the 1940s-1950s, leading to what is now called molecular mechanics force field (MMFF) calculations13. Thomas14 introduced MMFF94, the initial published version of the MMFF. It describes the objectives set for MMFF, the form it takes, and the range of systems to which it applies. This study also outlines the methodology employed in parameterizing MMFF94 and summarizes its performance in reproducing computational and experimental data.

172

J. Chem. Bio. Phy. Sci. Sec. A, February 2018 – April 2018, Vol. 8, No. 2; 171-185. DOI:10.24214/jcbps.A.8.2.17185.]

Structures …

Hanan M. Ali et al.

For the more, the (Z)-4-amino-3-hydroxy-2-((4-(N-(5-methylisoxazol-3-yl) sulfamoyl) phenyl) diazenyl) naphthalene-1-sulfonic acid (3) was synthesised15. The azo dye characterized by IR spectrum, visible spectrum and CHN. Theoretical studies also intended for (3); the results of ICM were displayed that the angle type in most of atoms were dihedral. But, the results of molecular structure and MM2 properties indicated that the azo dye has high close contacts of atoms and high VDW interactions. And these interactions were increased after MM2 minimization, the later was also effected by high steric (1235.782) energy. But, the results of MMFF94 minimization and MMFF94 minimization/ sampling were revealed that the minimization can attended successfully using MMFF94 minimization.15 MATERIAL AND METHOD Culture media: Nutrient Agar (NA) and Sabouraud Dextrose Agar (SDA) were used to culture the bacterial and fungal strains, whereas the antimicrobial activity was carried out using Mueller Hinton Agar (MHA) and Sabouraud Dextrose Agar (SDA). Procedure: Agar-Well diffusion method16 was applied by pouring 20 mL of MHA (medium pathogenic bacteria) and SDA (pathogenic fungi) for each petri dish 90 mm). The mediums irrigated with 0.1 mL of bacterial suspension and 0.1 μm of optical suspensions respectively at a wavelength (540 nm), using a spectrophotometer with spreader glass diffuser. The dishes leave for 15-30 minutes until dried and drilled (0.5 mm) using a sterile metal well. The azo dyes solutions (100 μL) were added to each well and the DMSO (100 μL) was used as a control. Finally, the dishes were heated at 37° C for 24 hours in incubator and the diameter was gauged the inhibition zone. RESULT AND DISSECTION Antimicrobial activity depend on detailed structures of two synthetic azo dyes,4 that characterized 4acetaminophenol-[2-(4-Azo)]-N-2-pyrimidinyl-benzenesulfonamide (1) and 4-acetaminophenol-[2-(4Azo)]-N-(5-methyl-3-isoxazolyl-bezenesulfonamide (2) were studied. The variation in the structures of (1) and (2) were occurred in the part x; (x= 2-pyrimidinyl and 5-methyl-3-isoxazolyl respectively), (Figures 1and 2).

Figure (1): The structure of (1).

173


Structures …

Hanan M. Ali et al.

Figure (2): The structure of (2).

Antimicrobial activity of (1) and (2) as seen in Figure (3) below, were carried out against two bacterial species; Staphylococcus aureus (NCTC 6571) and Escherichia coli (ATCC 25922) and fungus Candida albicans using Agar-well diffusion method17.

(1)

(1)

(2)

(2)

(2) a

(1)

b

c

Figure (3): Antimicrobial activities of (1) and (2) against (a) Staphylococcus aureus, (b) Escherichia coli and (c) Candida albicans. The minimum concentration of each azo dye was gave inhibition against fungal culture and exhibited very well microbial activities. However, the Candida albicans was resistant against (1) in contrast with (2), the later exhibiting activity of fungus as shown in Table (1) below.

174


Structures …

Hanan M. Ali et al.

Table (1): Diameter of inhibition zone of (1) and (2) against bacterial and fungal infections Id

(a) Staphylococcus aureus 15 5

Azo dyes (1) (2)

Inhibition zones (mm) (b) Escherichia coli 15

(c) Candida albicans 28 32

The table illustrates the inhibition zones (mm) of each synthetic azo dye against bacterial and fungal infections. Then, the structures of (1) and (2) were studied theoretically in order to understand this effect in their biological activity. Therefore, the actual and optimal bond lengths between atoms were calculated as realized in Table (2). Table (2): The actual and optimal bond lengths between atoms in azo dyes (1) and (2)

No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32

175

Atoms (1) C(29)-H(49) C(29)-H(48) C(29)-H(47) N(28)-H(46) N(28)-S(25) S(25)-O(27) S(25)-O(26) C(23)-O(24) C(29)-C(23) N(22)-H(45) N(22)-C(23) O(21)-H(44) N(19)-N(20) C(18)-H(43) C(17)-H(42) C(17)-C(18) C(16)-H(41) C(16)-C(17) C(16)-N(15) C(14)-N(15) C(14)-N(28) N(13)-C(14) C(18)-N(13) C(12)-H(40) C(11)-C(12) C(11)-S(25) C(10)-H(39) C(10)-C(11) C(9)-H(38) C(9)-C(10) C(8)-C(9) N(20)-C(8)

(2) C(29)-H(50) C(29)-H(49) C(29)-H(48) C(28)-H(47) C(28)-H(46) C(28)-H(45) C(26)-O(27) C(26)-C(29) C(25)-H(44) C(26)-C(25) C(24)-C(25) N(23)-C(24) O(27)-N(23) N(22)-H(43) N(22)-C(24) N(22)-S(19) S(19)-O(21) S(19)-O(20) C(17)-O(18) C(28)-C(17) N(16)-H(42) N(16)-C(17) O(15)-H(41) N(13)-N(14) C(12)-H(40) C(11)-C(12) C(11)-S(19) C(10)-H(39) C(10)-C(11) C(9)-H(38) C(9)-C(10) C(8)-C(9)

Bond Length Ǻ Actual Ǻ (1) (2) 1.113 1.113 1.113 1.113 1.113 1.113 1.05 1.113 1.696 1.113 1.45 1.113 1.45 1.357 1.208 1.497 1.509 1.1 1.012 1.37 1.369 1.406 0.972 1.335 1.248 1.387 1.1 1.05 1.1 1.266 1.376 1.696 1.1 1.45 1.376 1.45 1.346 1.208 1.342 1.509 1.266 1.012 1.342 1.369 1.346 0.972 1.1 1.248 1.395 1.1 1.79 1.395 1.1 1.79 1.395 1.1 1.1 1.395 1.395 1.1 1.395 1.395 1.26 1.395


Optimal Ǻ (1) (2) 1.113 1.113 1.113 1.113 1.113 1.113 1.05 1.113 1.113 1.45 1.113 1.45 1.323 1.208 1.497 1.509 1.1 1.012 1.42 1.369 1.42 0.972 1.358 1.248 1.1 1.05 1.1 1.462 1.42 1.1 1.45 1.42 1.45 1.358 1.208 1.358 1.509 1.462 1.012 1.358 1.369 1.358 0.972 1.1 1.248 1.42 1.1 1.42 1.1 1.42 1.1 1.1 1.42 1.42 1.1 1.42 1.42 1.456 1.42

Structures …

33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48

Hanan M. Ali et al.

C(7)-H(37) C(7)-C(12) C(7)-C(8) N(19)-C(6) C(5)-H(36) C(5)-C(6) C(4)-C(5) C(4)-N(22) C(3)-H(35) C(3)-C(4) C(2)-H(34) C(2)-C(3) C(1)-C(6) C(1)-C(2) C(1)-O(21)

N(14)-C(8) C(7)-H(37) C(7)-C(12) C(7)-C(8) N(13)-C(6) C(5)-H(36) C(5)-C(6) C(4)-C(5) C(4)-N(16) C(3)-H(35) C(3)-C(4) C(2)-H(34) C(2)-C(3) C(1)-C(6) C(1)-C(2) C(1)-O(15)

1.1 1.395 1.395 1.26 1.1 1.395 1.395 1.345 1.1 1.395 1.1 1.395 1.395 1.395 1.355

1.26 1.1 1.395 1.395 1.26 1.1 1.395 1.395 1.345 1.1 1.395 1.1 1.395 1.395 1.395

1.1 1.42 1.42 1.456 1.1 1.42 1.42 1.345 1.1 1.42 1.1 1.42 1.42 1.42 1.355 -

1.456 1.1 1.42 1.42 1.456 1.1 1.42 1.42 1.345 1.1 1.42 1.1 1.42 1.42 1.42 1.355

The table indicates that the actual and optimal bonds length of azo (-N=N-) group was equal to 1.248 Ǻ in each azo dye. However, the close contact of atoms in the structures of (1) and (2) were calculated, (Table 3). Table (3): Close contact of (1) and (2) No

Atoms of (1)

Atoms of (2)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

N(20)-H(40) N(15)-C(18) C(14)-C(17) N(13)-C(16) S(25)-N(15) H(31)-C(23) C(3)-C(23) C(9)-C(12) C(8)-C(11) N(19)-H(34) C(7)-C(10) N(19)-C(9) O(21)-N(20) C(1)-N(20) N(19)-O(21) C(3)-C(6) C(2)-C(5) C(1)-C(4)

N(14)-H(37) S(19)-H(40) S(19)-C(25) H(31)-C(17) C(3)-C(17) C(9)-C(12) C(8)-C(11) N(13)-H(34) C(7)-C(10) N(13)-C(9) O(15)-N(14) C(1)-N(14) N(13)-O(15) C(3)-C(6) C(2)-C(5) C(1)-C(4)

Actual close contact atoms Ǻ of (1) 1.214 2.717 2.687 2.717 2.736 2.385 2.727 2.79 2.79 2.03 2.79 2.333 2.039 2.333 2.704 2.79 2.79 2.79

Actual close contact atoms Ǻ of (2) 1.214 2.666 2.915 2.385 2.727 2.79 2.79 2.03 2.79 2.333 2.039 2.333 2.704 2.79 2.79 2.79

The table displays that the shortest non-bonded contact atoms in (1) and (2) was equal to 1.214 Ǻ, which was seemed to be higher than the closest allowed contact distance in the their structures. The maximum deviations of close contact atoms were calculated, for example the maximum deviation of C(9)-C(12) close contact atoms in (1) and (2), which equal to 2.790 Ǻ in each, from C-C bond which equal to 1.376 Ǻ and 1.012 Ǻ were corresponds to about 1.414 and 1.778 respectively. Add to which, the dihedral angles of (1) and (2) were calculated, the results were showed that the dihedral angles were in the range (±180), which indicated that the two synthetic azo dyes folding in a way same to 176


Structures …

Hanan M. Ali et al.

that presents in biomolecules18. Then, the conformational energies around C-C single bond in each side of azo (-N=N-) group were studied theoretically, the energies of C(7)-C(8)-N(20)-N(19) (a) and C(1)-C(6)-N(19)-N(20) (b) conformations in (1) and C(7)-C(8)-N(14)-N(13) (c) and C(1)-C(6)N(13)-N(14) (d) conformations in (2) were calculated as present in Figures (4) below.

Conformational Energy


b

a

620.0

Energy

Energy

616.0 612.0

605.0

607.0

590.0

602.0 -180 -135 -90 -45 0 45 90 135 180 C(7)-C(8)-N(20)-N(19)(degrees)

575.0 -180 -135 -90 -45 0 45 90 135 180 C(1)-C(6)-N(19)-N(20)(degrees) Conformational Energy

574.0

577.0

c

569.0

Energy

Energy


d 562.0

565.0

547.0

560.0 -180 -135 -90 -45 0 45 90 135 180 C(7)-C(8)-N(14)-N(13)(degrees)

532.0 -180 -135 -90 -45 0 45 90 135 180 C(1)-C(6)-N(13)-N(14)(degrees)

Figure (4): The energies of C(7)-C(8)-N(20)-N(19) (a) and C(1)-C(6)-N(19)-N(20) (b)conformations in (1) and C(7)-C(8)-N(14)-N(13) (c) and C(1)-C(6)-N(13)-N(14) (d) conformations in (2). The results were illustrated that the staggered and eclipsed conformations are interconverted by rotation about the C-C single bond with an energy difference, (Figure 4). Figure 4(a) displays that the higher energy eclipsed E for E(-180o), E(-40o) and E(140o) conformations, have torsional strain equal to 612.83, 620.33 and 620.22 kcal/ mole respectively. But, the lower energy staggered E(-140o), E(45o) and E(180o) conformations have torsional strain equal to 602.07, 602.23 and 612.83 kcal/ mole respectively. Then, figure 4(b) shows that the eclipsed E for E(-180o), E(-75o), E(-15o) and E(140o) conformations have torsional strain equal to 586.19, 588.37, 633.98 and 593.88 kcal/ mole respectively. But, the staggered E(-135o), E(-60o), E(50o) and E(180o) conformations have torsional strain equal to 574.54, 591.11, 576.69 and 586.19 kcal/ mole respectively. Then again, figure 4(c) demonstrates that the eclipsed E for E(-180o), E(-40o) and E(140o) conformations have torsional strain equal to 570.37, 577.85 and 577.76 kcal/mole respectively. But, the staggered E(-140o), E(40o) and E(180o) conformations have torsional strain equal to 559.61, 559.70 and 570.37 kcal/mole respectively. As well as, figure 4(d) indicates that the eclipsed E for E(-180o), E(-75o), E(-15o) and E(140o) conformations have torsional strain equal to 586.19, 588.37, 633.98 and 593.88 kcal/ mole respectively. But, the staggered E(-135o), E(-45o), E(50o) and E(180o) conformations have torsional strain equal to 532.11, 554.26, 534.32 and 543.76 kcal/ mole respectively. Thus, the ICM of (1) and (2) were also envisioned hypothetically, the results obtained before, (Tables 4 and 5 respectively) and after, (Tables 6 and 7 respectively) rotation around C-C signal bound.

177


Structures …

Hanan M. Ali et al.

Table (4): Internal coordinate (ICM) of (1)

No

Atom

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45

C(1) C(2) C(3) H(30) C(4) H(31) C(5) N(22) C(6) N(19) O(21) H(32) N(20) C(8) C(7) C(9) C(10) H(34) C(11) H(35) C(12) S(25) H(33) H(36) C(23) H(41) N(28) O(26) O(27) C(14) H(42) N(13) N(15) C(16) C(17) H(37) C(18) H(38) H(39) C(29) O(24) H(40) H(43) H(44) H(45)

178

Bond Atom

Bond Length (Ǻ)

Angle Atom

Angle ( )

C(1) C(2) C(2) C(3) C(3) C(4) C(4) C(1) C(6) C(1) C(5) N(19) N(20) C(8) C(8) C(9) C(9) C(10) C(10) C(7) C(11) C(7) C(12) N(22) N(22) S(25) S(25) S(25) N(28) N(28) C(14) C(14) N(15) C(16) C(16) N(13) C(17) C(18) C(23) C(23) O(21) C(29) C(29) C(29)

1.395 1.395 1.1 1.395 1.1 1.395 1.345 1.395 1.26 1.355 1.1 1.248 1.26 1.395 1.395 1.395 1.1 1.395 1.1 1.395 1.79 1.1 1.1 1.369 1.012 1.696 1.45 1.45 1.266 1.05 1.342 1.342 1.346 1.376 1.1 1.346 1.1 1.1 1.509 1.208 0.972 1.113 1.113 1.113

C(1) C(1) C(2) C(2) C(3) C(3) C(2) C(1) C(2) C(4) C(6) N(19) N(20) C(7) C(8) C(8) C(9) C(9) C(8) C(10) C(8) C(7) C(4) C(4) C(11) C(11) C(11) S(25) C(14) N(28) N(13) C(14) N(15) N(15) C(14) C(16) N(13) N(22) N(22) C(1) C(23) C(23) C(23)

119.997 120.002 120 120 120.003 119.998 120.003 120 119.999 120.002 107.5 107.5 120.001 119.997 120.001 119.999 120.001 119.999 120.003 120 119.999 120 120 120 109.462 109.5 109.442 120.001 120 116.97 126.063 115.609 123.545 118.228 115.611 122.186 118.227 120 120 108 109.5 109.442 109.461

o

2nd Angle Atom

2nd Angle (o)

2nd Angle Type

C(3) C(1) C(4) C(2) C(5) C(3) C(5) C(6) C(6) C(1) C(6) N(19) N(20) C(7) C(10) C(8) C(11) C(9) C(12) C(12) C(11) C(3) C(23) C(10) N(28) O(26) C(11) S(25) S(25) N(28) N(13) C(14) C(17) N(15) C(18) C(17) C(4) C(29) C(2) N(22) H(43) H(43)

120.001 -0.006 120 0.001 119.998 0.006 120 119.998 120.001 0 180 179.995 120.002 -0.006 120 0.001 120 0.006 120.001 119.999 120 0 120 -120.001 109.462 109.442 -179.999 120 -179.999 116.968 -0.008 0.006 118.228 0.005 122.184 118.23 -90 120.001 -180 0 109.442 109.462

Pro-R Dihedral Pro-R Dihedral Pro-R Dihedral Pro-S Pro-S Pro-R Dihedral Dihedral Dihedral Pro-R Dihedral Pro-R Dihedral Pro-S Dihedral Pro-R Pro-S Pro-R Dihedral Pro-R Dihedral Pro-S Pro-S Dihedral Pro-R Dihedral Pro-R Dihedral Dihedral Pro-S Dihedral Pro-R Pro-S Dihedral Pro-S Dihedral Dihedral Pro-S Pro-R


Structures …

Hanan M. Ali et al.

Table (5): Internal coordinate (ICM) of (2)

No

Atom

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46

C(1) C(2) C(3) H(30) C(4) H(31) C(5) N(16) C(6) N(13) O(15) H(32) N(14) C(8) C(7) C(9) C(10) H(34) C(11) H(35) C(12) S(19) H(33) H(36) C(17) H(38) N(22) O(20) O(21) C(24) H(39) N(23) C(25) C(26) H(40) O(27) C(29) C(28) O(18) H(37) H(41) H(42) H(43) H(44) H(45) H(46) 179

Bond Atom

Bond Length (Ǻ)

C(1) C(2) C(2) C(3) C(3) C(4) C(4) C(1) C(6) C(1) C(5) N(13) N(14) C(8) C(8) C(9) C(9) C(10) C(10) C(7) C(11) C(7) C(12) N(16) N(16) S(19) S(19) S(19) N(22) N(22) C(24) C(24) C(25) C(25) N(23) C(26) C(17) C(17) O(15) C(28) C(28) C(28) C(29) C(29) C(29)

1.395 1.395 1.1 1.395 1.1 1.395 1.345 1.395 1.26 1.355 1.1 1.248 1.26 1.395 1.395 1.395 1.1 1.395 1.1 1.395 1.79 1.1 1.1 1.369 1.012 1.696 1.45 1.45 1.266 1.05 1.335 1.406 1.37 1.1 1.387 1.497 1.509 1.208 0.972 1.113 1.113 1.113 1.113 1.113 1.113

Angle Atom

Angle ( )

C(1) C(1) C(2) C(2) C(3) C(3) C(2) C(1) C(2) C(4) C(6) N(13) N(14) C(7) C(8) C(8) C(9) C(9) C(8) C(10) C(8) C(7) C(4) C(4) C(11) C(11) C(11) S(19) S(19) N(22) N(22) C(24) C(24) C(24) C(25) N(16) N(16) C(1) C(17) C(17) C(17) C(26) C(26) C(26)

119.997 120.001 120 120 120.003 119.998 120.003 120 119.999 120.001 107.5 107.5 120.002 119.997 120 120 120.003 119.998 120.003 120.002 119.998 120 120 120 109.462 109.5 109.442 120 120 123.96 123.96 103.824 128.088 105.246 125.196 119.999 120.001 108 109.5 109.442 109.462 109.5 109.443 109.46

o

2nd Angle Atom

2nd Angle (o)

2nd Angle Type

C(3) C(1) C(4) C(2) C(5) C(3) C(5) C(6) C(6) C(1) C(6) N(13) N(14) C(7) C(10) C(8) C(11) C(9) C(12) C(12) C(11) C(3) C(17) C(10) N(22) O(20) C(11) C(24) S(19) N(23) N(22) C(26) N(22) O(27) C(4) C(28) C(2) N(16) H(41) H(41) C(25) H(44) H(44)

120.002 -0.006 120 0.001 119.998 0.006 120 119.999 120.002 -0.005 180 -180 120.002 -0.006 120 0.001 119.998 0.006 120.001 119.999 120 0 120 -120.001 109.462 109.442 180 120 -180 112.08 -180 128.088 -179.999 125.195 -90 120 -180 0 109.442 109.462 -180 109.44 109.464

Pro-S Dihedral Pro-S Dihedral Pro-R Dihedral Pro-R Pro-S Pro-R Dihedral Dihedral Dihedral Pro-R Dihedral Pro-R Dihedral Pro-S Dihedral Pro-R Pro-S Pro-S Dihedral Pro-S Dihedral Pro-S Pro-S Dihedral Pro-R Dihedral Pro-S Dihedral Pro-R Dihedral Pro-R Dihedral Pro-R Dihedral Dihedral Pro-S Pro-R Dihedral Pro-S Pro-R


Structures …

Hanan M. Ali et al.

Table (6): Internal coordinate (ICM) of (1) after rotation

No

Atom

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46

C(1) C(2) C(3) C(4) C(6) H(34) C(5) O(21) H(35) N(19) N(22) H(36) H(44) N(20) C(23) Lp(50) Lp(51) C(8) C(29) H(45) Lp(32) C(7) O(24) H(47) Lp(33) C(9) H(48) H(49) Lp(52) Lp(53) C(10) C(12) C(11) H(37) H(38) S(25) H(39) H(40) N(28) C(14) O(26) N(13) O(27) H(46) Lp(54) Lp(55) 180

Bond Atom

Bond Length (Ǻ)

Angle Atom

Angle ( )

C(1) C(2) C(3) C(1) C(2) C(4) C(1) C(3) C(6) C(4) C(5) O(21) N(19) N(22) O(21) O(21) N(20) C(23) N(22) N(19) C(8) C(23) C(29) N(20) C(8) C(29) C(29) O(24) O(24) C(9) C(7) C(10) C(7) C(9) C(11) C(10) C(12) S(25) N(28) S(25) C(14) S(25) N(28) O(26) O(26)

1.395 1.395 1.395 1.395 1.1 1.395 1.355 1.1 1.26 1.345 1.1 0.972 1.248 1.369 0.6 0.6 1.26 1.509 1.012 0.6 1.395 1.208 1.113 0.6 1.395 1.113 1.113 0.6 0.6 1.395 1.395 1.395 1.1 1.1 1.79 1.1 1.1 1.696 1.266 1.45 1.342 1.45 1.05 0.6 0.6

C(1) C(2) C(2) C(1) C(3) C(2) C(2) C(1) C(3) C(4) C(1) C(6) C(4) C(1) C(1) N(19) N(22) C(4) C(6) N(20) N(22) C(23) C(8) C(7) C(23) C(23) C(23) C(23) C(8) C(8) C(9) C(8) C(8) C(10) C(9) C(7) C(11) S(25) C(11) N(28) C(11) C(14) S(25) S(25)

119.997 120 120.003 120.002 120.003 119.998 120 120 119.998 120.001 108 107.5 120 109.815 110.335 107.5 120 120 109.939 120.002 120 109.501 109.939 119.997 109.442 109.462 120 109 120 120.003 120.003 119.998 120 120.002 119.999 120 109.462 120 109.5 116.968 109.442 120 120 120

o

2nd Angle Atom

2nd Angle (o)

2nd Angle Type

C(1) C(3) C(3) C(2) C(6) C(4) C(5) C(5) C(6) C(2) C(1) C(3) H(44) H(44) C(6) C(4) C(23) N(20) N(19) C(29) N(22) N(19) N(20) H(47) H(47) N(22) N(22) C(7) C(9) C(8) C(12) C(10) C(12) C(11) C(11) C(10) C(11) N(28) S(25) O(26) S(25) C(11) C(11)

-0.006 0.006 120.001 0.001 119.999 120 120 119.998 120.002 180 0 0 109.815 110.335 -180 -90 120 109.939 179.995 120 0.001 109.939 120.001 109.441 109.462 -180 0 -0.006 0.006 0.001 119.999 120 120.001 119.998 120 -120 -180 109.462 -180 109.442 120 -180 0

Dihedral Dihedral Pro-R Dihedral Pro-R Pro-R Pro-R Pro-R Pro-R Dihedral Dihedral Dihedral Pro-S Pro-R Dihedral Dihedral Pro-R Pro-S Dihedral Pro-R Dihedral Pro-S Pro-S Pro-S Pro-R Dihedral Dihedral Dihedral Dihedral Dihedral Pro-R Pro-S Pro-S Pro-R Pro-R Dihedral Dihedral Pro-S Dihedral Pro-S Pro-S Dihedral Dihedral


Structures …

47 48 49 50 51 52 53 54 55 56 57

N(15) Lp(56) Lp(57) C(16) C(18) C(17) Lp(30) Lp(31) H(41) H(42) H(43)

Hanan M. Ali et al.

C(14) O(27) O(27) N(15) N(13) C(16) N(13) N(15) C(16) C(17) C(18)

1.342 0.6 0.6 1.346 1.346 1.376 0.6 0.6 1.1 1.1 1.1

N(13) S(25) S(25) C(14) C(14) N(15) C(14) C(14) N(15) C(16) N(13)

126.063 120 120 115.609 115.611 123.544 107.895 107.895 118.228 122.185 118.229

N(28) C(11) C(11) N(13) N(15) C(14) C(18) C(16) C(17) C(18) C(17)

116.968 180 0 -0.003 0.002 0.002 107.895 107.895 118.227 122.185 118.229

Pro-R Dihedral Dihedral Dihedral Dihedral Dihedral Pro-S Pro-S Pro-S Pro-S Pro-R

Table (7): Internal coordinate (ICM) of (2) after rotation

No

Atom

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33

C(1) C(2) C(3) C(4) C(6) H(34) C(5) O(15) H(35) N(13) N(16) H(36) H(41) N(14) C(17) Lp(32) Lp(33) C(8) C(28) H(42) Lp(30) C(7) O(18) H(45) Lp(31) C(9) H(46) H(47) Lp(51) Lp(52) C(10) C(12) C(11) 181

Bond Atom

Bond Length (Ǻ)

Angle Atom

Angle (o)

C(1) C(2) C(3) C(1) C(2) C(4) C(1) C(3) C(6) C(4) C(5) O(15) N(13) N(16) O(15) O(15) N(14) C(17) N(16) N(13) C(8) C(17) C(28) N(14) C(8) C(28) C(28) O(18) O(18) C(9) C(7) C(10)

1.395 1.395 1.395 1.395 1.1 1.395 1.355 1.1 1.26 1.345 1.1 0.972 1.248 1.369 0.6 0.6 1.26 1.509 1.012 0.6 1.395 1.208 1.113 0.6 1.395 1.113 1.113 0.6 0.6 1.395 1.395 1.395

C(1) C(2) C(2) C(1) C(3) C(2) C(2) C(1) C(3) C(4) C(1) C(6) C(4) C(1) C(1) N(13) N(16) C(4) C(6) N(14) N(16) C(17) C(8) C(7) C(17) C(17) C(17) C(17) C(8) C(8) C(9)

119.998 119.997 120.005 120.001 120.005 120.001 120.001 120.002 119.997 120.001 108.002 107.502 120 109.814 110.333 107.502 120.001 120 109.939 120.002 120.003 109.501 109.939 119.997 109.442 109.461 120 109 120 120.003 120.003

2nd Angle Atom

2nd Angle (o)

2nd Angle Type

C(1) C(3) C(3) C(2) C(6) C(4) C(5) C(5) C(6) C(2) C(1) C(3) H(41) H(41) C(6) C(4) C(17) N(14) N(13) C(28) N(16) N(13) N(14) H(45) H(45) N(16) N(16) C(7) C(9) C(8)

-0.006 0.006 120.001 0.001 119.994 120.001 120 119.998 120.002 -180 -0.005 0 109.814 110.333 180 -89.999 120 109.939 -180 119.996 0 109.939 120.001 109.441 109.46 180 0 -0.006 0.006 0.001

Dihedral Dihedral Pro-S Dihedral Pro-S Pro-S Pro-R Pro-R Pro-R Dihedral Dihedral Dihedral Pro-S Pro-R Dihedral Dihedral Pro-R Pro-S Dihedral Pro-S Dihedral Pro-S Pro-S Pro-S Pro-R Dihedral Dihedral Dihedral Dihedral Dihedral


Structures …

34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58

H(37) H(38) S(19) H(39) H(40) N(22) O(20) C(24) O(21) N(23) H(43) Lp(53) Lp(54) C(25) O(27) Lp(55) Lp(56) C(26) Lp(57) C(29) H(44) Lp(58) H(48) H(49) H(50)

Hanan M. Ali et al.

C(7) C(9) C(11) C(10) C(12) S(19) S(19) N(22) S(19) C(24) N(22) O(20) O(20) C(24) N(23) O(21) O(21) C(25) N(23) C(26) C(25) O(27) C(29) C(29) C(29)

1.1 1.1 1.79 1.1 1.1 1.696 1.45 1.266 1.45 1.335 1.05 0.6 0.6 1.406 1.387 0.6 0.6 1.37 0.6 1.497 1.1 0.6 1.113 1.113 1.113

C(8) C(8) C(10) C(9) C(7) C(11) C(11) S(19) C(11) N(22) S(19) S(19) S(19) N(22) C(24) S(19) S(19) C(24) C(24) C(25) C(24) N(23) C(26) C(26) C(26)

119.998 120 120.002 119.999 120 109.462 109.5 120 109.442 123.96 120 120 120 123.96 105.246 120 120 103.824 110.493 125.195 128.088 109.507 109.5 109.442 109.462

C(12) C(10) C(12) C(11) C(11) C(10) N(22) C(11) O(20) S(19) C(24) C(11) C(11) N(23) N(22) C(11) C(11) N(22) O(27) O(27) C(26) C(26) C(25) H(48) H(48)

119.999 120 120.001 119.998 120 -120 109.462 -180 109.442 180 120 180 0 112.081 -180 -180 0 -179.999 110.493 125.195 128.088 109.507 -180 109.441 109.462

Pro-S Pro-R Pro-R Pro-S Pro-S Dihedral Pro-S Dihedral Pro-S Dihedral Pro-S Dihedral Dihedral Pro-S Dihedral Dihedral Dihedral Dihedral Pro-S Pro-R Pro-R Pro-R Dihedral Pro-S Pro-R

Tables (6) and (7) were indicated that the conformational analysis of synthetic azo dye can affect their ICM, due to affect their properties, binding and biological activity subsequently. Furthermore, the MM2 properties was intended for (1) and (2), the results showed that the (stretch: 45.8638, bend: 318.2066, stretch-bend:-0.2599, torsion: 181.5290, Non-1,4 VDW: 44.5307, 1,4 VDW: 25.8409, dipole/ dipole: -2.8761 and total energy: 612.8350 kcal/ mol) and the (stretch: 46.6635, bend: 325.4775, stretch-bend: -1.7085, torsion: 135.9717, Non-1,4 VDW: 46.3284, 1,4 VDW: 21.0006, dipole/ dipole: -3.3589 and total energy: 570.3743 kcal/ mol) respectively. The results were also demonstrated that the stretch, bend, stretch-bend and Non-1,4 VDW values of (1) seems to be lower than (2), but the torsion, 1,4 VDW, dipole/ dipole and total energy values of (1) were higher than (2). In contrast of these results with that received by antimicrobial activity, we find that the low concentration of each azo dye was given reasonable and variable reactivates. The MM2 properties of 2-pyrimidinyl and 5-methyl-3-isoxazolyl (part x) in (1) and (2) respectively were also intended, the results were showed that the (stretch: 21.1387, bend: 4.0772, stretch-bend: 0.0082, torsion: 60.9597, Non-1,4 VDW: -0.3427, 1,4 VDW: 3.8389, dipole/ dipole: -0.0317 and total energy: 89.6482 kcal/ mol) and (stretch: 21.9329, bend: 14.1072, stretch-bend: -1.5580, torsion: 16.4623, Non-1,4 VDW: 0.4616, 1,4 VDW: 0.3519, dipole/ dipole: 0.0740 and total energy: 50.9087 kcal/mol) respectively. Further, the biological activity and the total energies of (1) and (2) were studied as seen in Figure (5) below.

182


Structures …

Hanan M. Ali et al. Candida albicans 40

Staphylococcus aureus

Escherichia coli

Biological activity

35 30 25 20 15 10 5 0 612.835

570.3743

1

2 Total Energy (kcal/ mol)

Figure (5): The biological activity of (1) and (2). The figure illustrates that the best antimicrobial activity of each azo dye was remained against fungal infection. Also, the Candida albicans and Escherichia coli were inhibited by low energy azo dye (2) more than high energy azo dye (1), the latter is resisting action of Escherichia coli. Further, the MM2 minimization for (1) and (2) were calculated, the results were showed that the (stretch:, 1.4631 bend: 144.2188, stretch-bend: -0.1458, torsion: 30.6399, non-1,4 VDW: -3.5324, 1,4 VDW: 22.7469, dipole/ dipole: -2.4708 and total energy 192.9198 kcal/ mol) and the (stretch: 1.2307, bend: 151.9259, stretch-bend: -0.2032, torsion: 28.4755, non-1,4 VDW: -3.4265, 1,4 VDW: 16.0604, dipole/ dipole: -0.8864 and total energy: 193.1764 kcal/ mol) respectively, the steric effect was increased after MM2 minimization in (2). The MMFF94 minimization iteration was also calculated, this minimization terminated normally because the gradient norm is less than the minimum gradient norm and the final energies of (1) and (2) were equal to -87.4877 kcal/ mol and -53.1368 kcal/ mol respectively. Thus, the final energies of MMFF94 minimization/ sampling of (1) and (2) were equal to -87.5526 kcal/ mol and -53.2344 kcal/ mol respectively. These results were showed that the MMFF94 minimizations were attended successfully for each azo dye. CONCLUSIONS This study was focused on the extent of antimicrobial activity; which remained contingent on structures of synthetic azo dyes, which have different rings and different steric energies. The structure of each azo dye was affected by conformational analysis, which affects their molecular mechanics and internal coordinate, due to affect their properties, binding and biological activity subsequently. Therefore, we recommend these azo dyes as a novel candidate for targeting microorganisms. REFERENCES 1. B. Kirkan, R. Gup, Synthesis of New Azo Dyes and Copper (II) Complexes Derived from Barbituric Acid and 4-Aminobenzoylhydrazone. Turk. J. Chem. (2008), 32: 9 – 7.

183


Structures …

Hanan M. Ali et al.

2. H. Zollinger, Color chemistry; synthesis, properties and Application of organic Dyes and Pigments, Weinheim, New York,(1991). 3. J. Otutu, Synthesis and application of azo dyes derived from 2-amino-1, 3,4-thiadiazole2-thiol on polyester fibre'', J. IJRRAS (2013), 15: 292 – 296. 4. H. Majeed, Synthesis, Characterization and study of the spectral and electronic properties of a New Azo Dyes Compounds, J. Thi-Qar Sci (2013), 4: 91 – 101. 5. J. Fox, J. Chem. Soc. (1910), 97: 1339 (b) H. Majeed, A. Al-Ahmad, K. Hussain, The Preparation, Characterization and the Study of the Linear Optical Properties of a New Azo Compound, Journal of Basrah Researches ((Sciences)) (2011), 37: 64 – 73. 6. D. Schwieters, M. Clore, Internal Coordinates for Molecular Dynamics and Minimization in Structure Determination and Refinement, Journal of magnetic resonance (2001),152: 288 –302. 7. N. Vaidehi, A. Jain, Internal coordinate molecular dynamics: A foundation for multiscale dynamics, Journal of Physical chemistry (2015), 119: 1233 – 1242. 8. A. Alexandros, N. Phuong, H. Rainer, S. Gerhard, Dihedral angle principal component analysis of molecular dynamics simulations, The Journal of chemical physics (2007), 126: 244 – 111. 9. F. Fayadh, A. Ali, F. Al –Jabri, Synthesis and Identification Symmetrically Azo Dyes Derived from Sulfa Compounds and Spectrophotometric study of Nickel (II) Complexes with Prepared Dyes, International Journal of Engineering and Technical Research (IJETR) (2015), 3: 25 – 28. 10. H. Ali, Synthesis, theoretical studies of N1,N2,1,2-tetraphenylethane-1,2-diimine and their Derivatives, The International Institute for Science, Technology and Education (IISTE) (2016), 8: 91 – 99. 11. T. Stan (2003) An Introduction to Computational Biochemistry; Molecular modeling: molecular mechanics, New York, United States. 12. J. Ponder, F. Richards, An efficient newton-like method for molecular mechanics energy, Journal of Computational Chemistry (1987), 8: 1016 – 1024. 13. L. David, G. Jerome (2000) Organic Conformational Analysis and Stereochemistry from Circular Dichroism Spectroscopy, Wiley, New York. 14. A. Thomas, Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94, Journal of Computational Chemistry (1996), 17: 490 – 519. 15. H. Ali, H. Majeed, A. Hussain, Synthesis, Analytical and Theoretical studies of (Z)-4amino-3-hydroxy-2-((4-(N-(5-methyl isoxazol-3yl) sulfamoyl) phenyl) diazenyl) naphthalene-1-Sulfonic Acid, Journal of Natural Sciences Research (2017), 7: 81 – 88. 16. C. Rabinovitz, D. Pogni, M. Pogni, S. Hauschild (1979) Medical Microbiology, Pathological Society of Great Britain and Ireland, Churchill, Livingstone.

184


Structures …

Hanan M. Ali et al.

17. C. Perez, M. Paul, P. Bazerque, Antibiotic assay by agar well diffusion method, Acta Biol Med Exp. (1990), 15: 113 – 115. 18. H. Ali, Theoretical Studies of Trans-Alkene Mycolic Acid, Journal of Natural Sciences Research (2016), 6: 54 – 63.

Corresponding author: Hanan M. Ali, Department of Chemistry, College of Education for Pure Sciences, University of Basrah Iraq Online publication Date: 24.03.2018

185
