Lupine Publishers | Spectroscopy and Dipole Moment of the Molecule C13H20BeLi2SeSi Via Quantum Chemistry using Ab Initio, Hartree-Fock Method in the Base Set CC-Pvtz and 6-311G**(3df, 3pd)

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Abstract

The work characterizes the electric dipole moment and the infrared spectrum of the molecule C₁₃H₂₀BeLi₂SeSi. Calculations obtained in the ab initio RHF (Restrict Hartree-Fock) method, on the set of bases used indicate that the simulated molecule C₁₃H₂₀BeLi₂SeSi features the structure polar-apolar-polar predominant. The set of bases used that have are CC-pVTZ and 6-311G** (3df, 3pd). In the CC-pVTZ base set, the charge density in relation to 6-311G** (3df, 3pd) is 50% lower. The length of the molecule C₁₃H₂₀BeLi₂SeSi is of 15.799Å. The magnitude of the electric dipole moment || total obtained was p = 4.9771 Debye and p = 4.7936 Debye, perpendicular to the main axis of the molecule, for sets basis CC-pVTZ and 6-311**(3df, 3pd), respectively. The infrared spectra for absorbance and transmittance and their wavenumber (cm^-1) were obtained in the set of bases used. The infrared spectrum for Standard CC-pVTZ shows peaks in transmittance with Intensity (I), at wavenumber 1,125.44cm^-1, 1,940.70cm^-1, 2,094.82cm^-1, 2,178.43cm^-1, 2,613.99cm^-1 and transmittance 433.399km/mol, 399.425km/mol, 361.825km/mol, 378.993km/ mol, 433.774km/mol, respectively. While the infrared spectrum for Standard 6-311G** (3df,3pd), shows peaks in transmittance, at wavelengths 1,114.83cm^-1, 1,936.81cm^-1, 2,081.49cm^-1, 2,163.23 cm^-1, 2,595.24cm^-1 and transmittance 434.556 km/mol, 394.430 km/mol, 345.287 km/mol, 375.381 km/mol, 409.232 km/mol, respectively. It presents “fingerprint” between the intervals (680cm- 1 and 1,500 cm^-1) and (3,250cm^-1 and 3,500cm^-1). The dipole moments CC-pTZV are 3.69% bigger than 6-311G (3df, 3pd). As the bioinorganic molecule C₁₃H₂₀BeLi₂SeSi is the basis for a new creation of a bio-membrane, later calculations that challenge the current concepts of biomembrane should advance to such a purpose.

Introduction

The work characterizes the electric dipole moment and the infrared spectrum of the molecule C₁₃H₂₀BeLi₂SeSi [1]. Using a computational simulation using ab initio methods, RHF (Restrict Hartree-Fock), [2-9] set of basis CC-pVTZ [10-14] and 6-311G (3df, 3pd) [7,5-21]. Preliminary bibliographic studies did not reveal any works with characteristics studied here. There is an absence of a referential of the theme, finding only one work in [1]. To construct such a molecule, which was called a seed molecule, quantum chemistry was used by ab initio methods [2,3,15]. The equipment used was of the Biophysics laboratory built specifically for this task. The results were satisfactory. The ab initio calculations, by RHF [2-9] in the CC-pVTZ [10-14] and 6-311G (3df, 3pd) [7,15- 21], sets basis was shown to be stable by changing its covalent cyclic chain linkages, which was expected. The set of basis used was that of Ahlrichs and coworkers the TZVP keywords refer to the initial formations of the split valence and triple zeta basis sets from this group [22,23]. The structure of the C₁₃H₂₀BeLi₂SeSi is a Bio-inorganic seed molecule for a biomembrane genesis that defies the current concepts of a protective mantle structure of a cell such as biomenbrane to date is promising, challenging. Leaving to the Biochemists their experimental synthesis. The quantum calculations must continue to obtain the structure of the bioinorganic biomenbrane. The following calculations, which are the computational simulation via Mm+, QM/MM, should indicate what type of structure should form. Structures of a liquid crystal such as a new membrane may occur, micelles [1,24-62].

Methods

Hartree-Fock Methods

Hartree-Fock theory is one the simplest approximate theories for solving the many-body Hamiltonian [2-9]. The full Hartree-Fock equations are given by

The vast literature associated with these methods suggests that the following is a plausible hierarchy:

The extremes of ‘best’, FCI, and ‘worst’, HF, are irrefutable, but the intermediate methods are less clear and depend on the type of chemical problem being addressed. [63,64] The use of HF in the case of FCI was due to the computational cost [1, 24-62].

Hardware and Software

For Calculations A Computer Models was Used: Intel® CoreTM i3-3220 CPU@3.3 GHz x 4 processors [65], Memory DDR3 4 GB, HD SATA WDC WD7500 AZEK-00RKKA0 750.1 GB and DVDRAM SATA GH24NS9 ATAPI, Graphics Intel® Ivy Bridge [66]. The ab initio calculations have been performed to study the equilibrium configuration of C₁₃H₂₀BeLi₂SeSi molecule using the GAMESS [15,20]. The set of programs Gauss View 5.0.8 [67], Mercury 3.8 [68], Avogadro [69,70] are the advanced semantic chemical editor, visualization, and analysis platform and GAMESS [15,20] is a computational chemistry software program and stands for General Atomic and Molecular Electronic Structure System [15,20] set of programs. For calculations of computational dynamics, the Ubuntu Linux version 16.10 system was used [71].

Discussion

The Figure 1 shows the final stable structure of the bioinorganic C₁₃H₂₀BeLi₂SeSi molecule obtained by an ab initio calculation with the method RHF (Restrict Hatrree-Fock), in sets of bases such as: 6-311G**(3df,3pd) and CC-pVTZ. As an example of analysis the set of bases CC-pVTV, with the charge distribution (Δδ) through it, whose charge variation is Δδ = 0.680 a.u. of elemental charge. In green color the intensity of positive charge displacement. In red color the negative charge displacement intensity. Variable, therefore, of δ- = 0.340 a.u. negative charge, passing through the absence of charge displacement, represented in the absence of black - for the green color of δ+ = 0.340 a.u. positive charge. The magnitude of the electric dipole moment || total obtained was p =4.9771 Debye, perpendicular to the main axis of the molecule, for sets basis CC-pVTZ. By the distribution of charge through the bioinorganic molecule it is clear that the molecule has a polar-apolarpolar structure, Figure 2 and Table 1. An analysis of the individual charge value of each atom of the molecule could be made, but here it was presented only according to Figure 2, due to the objective being to determine the polar-apolar-polar, the polar characteristic of the molecule, whose moment of dipole is practically perpendicular to the central axis of the molecule. In Figure 2 the dipole moment is visualized 6-311G**(3df,3pd) and CC-pVTZ in base sets, being represented by an arrow in dark blue color, with their respective values in Debye. This also presents the orientation axes x, y and z and the distribution of electric charges through the molecule.

In the set of bases used the CC-pTZV and 6-311**(3df, 3pd) present the same characteristic for the distribution of charges to the polar end with Carbon atom (negative charge) bound to the -SiH3 radical and the two Lithium atoms. It is seen that Δδ =0.680 a.u. of CC-pTZV and Δδ =1.366 a.u. of 6-311 (3df, 3pd), this latter has a twice greater Δδ, Figure 2, although the dipole moments CC-pTZV are 3.69% larger, (Table 1). The main chain (backbone of the molecule) for the CC-pTZV base set has a small negative charge displacement for the Carbon atoms from the Hydrogen atoms attached to them. Therefore, with positive charge the Hydrogen atoms connected to the Carbon of the central chain. For the set of bases 6-311**(3df, 3pd) the carbon atoms of the main chain are presented with very small distribution of negative charge, coming from the Hydrogen linked to these neutrals, Figure 2. At the other polar end for the base set 6-311**(3df, 3pd) the cyclic chain shows the characteristics as the Beryllium atom with strong charge displacement positive, these charges shift to the Carbon atoms attached to it, Figure 2. The cyclic chain with a strong negative charge, displaced from the Beryllium atom. The two carbon atoms bonded in double bonds, present a slight positive charge, with their neutral Hydrogen, Figure 2. The Selenium atom connected to two Carbon atoms of the cyclic chain presents a slight negative charge, originating from the Carbon atom connected to the main chain with a slight positive charge, and the other Carbon atom connected to the cyclic chain presents a neutral charge, Figure 2. The magnitude of the electric dipole moment || total obtained was p = 4.7936 Debye for 6-311**(3df, 3pd), (Table 1). Figures 3 & 4 represent the normalized infrared spectrum for the base set RHF / 6-311G ** (3df, 3pd) and CC-pVTZ for Absorbance and Transmittance. Figures 5 represent the normalized infrared spectrum for the base set RHF/6-311G** (3df, 3pd and CC-pVTZ for absorbance, making a comparison between the two sets of base. The infrared spectrum for Standard RHF/CC-pVTZ shows peaks in transmittance, at wavelengths 1,125.44cm^-1, 1,940.70cm- 1, 2,094.82cm^-1, 2,178.43cm^-1, 2,613.99cm^-1 and transmittance 433.399km/mol, 399.425km/mol, 361.825km/mol, 378.993km/ mol, 433.774km/mol, respectively, Figure 3 and Table 2. The infrared spectrum for Standard RHF/6-311G**(3df,3pd) shows peaks in transmittance, at wavelengths 1,114.83cm^-1, 1,936.81cm- 1, 2,081.49cm^-1, 2,163.23 cm^-1, 2,595.24cm^-1 and transmittance 434.556km/mol, 394.430 km/mol, 345.287 km/mol, 375.381 km/ mol, 409.232 km/mol, respectively, Figure 4 and Table 3. It presents “fingerprint” between the intervals (680cm^-1 and 1,500cm^-1) and (3,250cm^-1 and 3,500cm^-1), Figures 3-5.

Conclusion

Calculations obtained in the ab initio RHF method, on the set of bases used, indicate that the simulated molecule, C₁₃H₂₀BeLi₂SeSi, is acceptable by quantum chemistry. Its structure has polarity at its ends, having the characteristic polar-apolar-polar. The 6-311G (3df, 3pd) set of basis exhibits the characteristic of the central chain, with a small density of negative charges, near the ends of the Carbons of this. In the CC-pVTZ base set, the charge density in relation to 6-311G (3df, 3pd) is 50% lower. It is characterized infrared spectrum of the molecule C₁₃H₂₀BeLi₂SeSi, for absorbance and transmittance, in Hartree method in the set of bases CC-pVTZ and 6-311G (3df, 3pd). The infrared spectrum for Standard RHF/ CC-pVTZ shows peaks in transmittance, at wavelengths 1,125.44cm- 1, 1,940.70cm^-1, 2,094.82cm^-1, 2,178.43cm^-1, 2,613.99cm^-1 and transmittance 433.399 km/mol, 399.425km/mol, 361.825km/ mol, 378.993km/mol, 433.774km/mol, respectively. The infrared spectrum for Standard RHF/6-311G**(3df,3pd) [7,30,60,71,72] shows peaks in transmittance, at wavelengths 1,114.83cm- 1, 1,936.81cm^-1, 2,081.49cm^-1, 2,163.23cm^-1, 2,595.24cm^-1 and transmittance 434.556km/mol, 394.430km/mol, 345.287km/ mol, 375.381km/mol, 409.232km/mol, respectively. It presents “fingerprint” between the intervals (680cm^-1 and 1,500cm^-1) and (3,250cm^-1 and 3,500cm^-1). The dipole moments CC-pTZV are 3.69% bigger than 6-311G (3df, 3pd). As the bio-inorganic molecule C₁₃H₂₀BeLi₂SeSi is the basis for a new creation of a biomembrane, later calculations that challenge the current concepts of biomembrane should advance to such a purpose.

Acknowledgement

To the doctors: Prof. Ph.D. Tolga Yarman, Okan University, Akfirat, Istanbul, Turkey & Savronik, Organize Sanayi Bolgesi, Eskisehir, Turkey, and Prof. Ph.D. Ozan Yarman, Istanbul University, Rihtim Nr:1, 81300 Kadikoy, Istanbul, Turkey, for their valuable contributions to the work.

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Lupine Publishers | Metals Phytotoxicity Assessment and Phyto Maximum Allowable Concentration

 Lupine publishers | An archive of organic and inorganic chemical sciences

Abstract

In this paper, the influence of metals (Cd, Pb, Cu, Co, Ni, Zn) on plants of spring barley (Hordeum vulgare L.) was investigated in polluted sod podzolic sandy loam on layered glacial sands and calcareous deep chernozem on loamy loess soils. We propose to highlight the metals’ phytotoxicity with help of the Phyto Maximum Allowable Concentration. The Phyto Maximum Allowable Concentration is a permissible level of metals for plants in polluted soil and represents the safe degree for plants in contaminated ecosystem. The Phyto Maximum Allowable Concentration gives the possibility to estimate and to forecast the danger of metals for plants as a biological object that plays a very important role in the life of ecosystem. This approach may be applied for another metals phytotoxicity assessment for other plants.

Keywords:Metals; Plants; Phyto Maximum Allowable Concentration; Assessment, Pollution; Phytotoxicity

Introduction

Metals are significant environmental pollutants, and their toxicity is a problem of increasing significance for ecological, evolutionary, nutritional and environmental reasons Nagajyoti [1]; Bieby Voijant Tangahu [2]; Mamatha [3]; Metals, such as cadmium, copper, lead, nickel, cobalt and mercury are major environmental pollutants, particularly in areas with high anthropogenic pressure. Metal accumulation in soils and plants is of concern in agricultural production due to the adverse effects on food safety and marketability, crop growth due to phytotoxicity, and environmental health of soil organisms. The influence of plants and their metabolic activities affects the geological and biological redistribution of heavy metals through pollution of the air, water and soil Nagajyoti [1]; Gyuricza [4] Anthropogenic metals contamination of ecosystems as a result of the application of industrial, transport, agrarian and other technologies causes a damage of the functioning of plants as an important component in ecosystem Bradl[5]; Alloway [6]; Kabata-Pendias [7] Often plants are the main accumulator of metals in polluted ecosystem. In the same time, plants play an important role in ecosystem as biomass producers and as biodiversity creators Rombke [8]; Kabata-Pendias [7]; Sardar [9]. Usually phytotoxicity is considered as a harmful influence of metal on plant growth and development Kabata Pendias [7]; Nagajyoti [1]; Satpathy[10]; Gill [11] . However, the setting of a safe level of toxicant for the plant is also very important, because it can help to prevent and to control the negative effects of metals in the ecosystem. Today a methodology that would determine the safe concentration of metals directly for plants in the soil is absent. After all, the existing standards for the content of metals in environmental objects are sanitary-hygienic and focused just on human health Lewis [12]; Smirnov [13]; Warne [14]. Determination of the metals safe level in the soil for plants can help to objectively assess state of the ecosystem and prevent the metals dangerous influence on plant Ryzhenko [15]. The Phyto Maximum Allowable Concentration (PMAC) was suggested as safe level of metal in the soil for plants.

Materials and Methods

Spring barley (Hordeum vulgare L.) was selected as a model plant. Spring barley (Hordeum vulgare L.) is one of the important cereals crop in Ukraine. Mean standard deviations, variance, and minimum, maximum, standard errors were calculated from at least three replicates. The experimental results were interpreted using standard statistical methods. The soils of experimental pots were: sod podzolic sandy loam on layered glacial sands (sod podzolic) and calcareous deep chernozem on loamy loess (chernozem). Sod podzolic soil has the following physic chemical characteristics: pHsalt 5,5; organic matter by Turin 0,87%, CEC 6,3mg eqv/100g. Chernozem soil has the following: pHsalt 6,2, organic matter by Turin 2,89%, CEC 27,1mg eqv/100g. Background concentration of metals in soil (1 M HCl, mg kg-1) was: Cd - 0,1; Pb - 0.3; Cu = 0.92; Zn - 2.4; Ni - 1.1; Co-1,5 (sod podzolic); Cd = 0.11; Pb - 0.32; Cu - 2.6; Zn - 5.3; Ni - 2.3; Co - 2,5 (chernozem). Studied trace elements: Cd, Pb, Zn, Cu, Co, Ni were applied separately in amount equal to the following concentration in the soils.

That amount corresponds with adopted in Ukraine Maximum Allowed Concentration (MAC) in soil (Medvedev [16]. The following metals salts: Pb(NO3)2, ZnSO₄. H₂O, CuSO₄.7H₂O, CdSO4, NiSO4·6H₂O, CoSO4·7H₂O were used for the trace elements application. The investigation was conducted in green house conditions. Plants grew in plastic Mitcherlikh’s pots. Soil preparation, pots filling, and trials were carried out in accordance with standard methodic Dospekhov [17]; Medvedev [16]. The metals were added to soil during soil preparation before filling the pots. Then, spring barley germinated seeds were planted into the pots and, in the stage of 3 leaves, the recommended population was established. The studied elements were extracted by 1 M HCl from the soils. The method of HM determination was thin layer chromatography (TLC). Method widely was used in our previous investigation and officially recognized in Ukraine Kavetsky [18].

Results and Discussion

In this study, the algorithm of calculation of PMAC was proposed similar to the existing approach of calculation of Maximum Allowable Toxic Concentration (MATC) (equation 1) Rand [19]. In the toxicology practice, the scheme to substance toxicity assessment using the LOEC and NOEC is quite effective and widely used Smirnov [12]; Warne [13] Environment Canada. Guidance document on statistical methods for Environmental Toxicity Tests [20]; Globally Harmonized System of Classification and Labeling of Chemicals (GHS), fourth revised version, [21]. These indicators are used also for calculate the Maximum Allowable Toxic Concentration (MATC) on behalf of assessing the toxicity of substances in the aquatic environment. MATC is calculated by the formula Rand [19]:

MATC=√((NOEC)*(LOEC)) , (1)

where NOEC is No Observed Effect Concentration.

LOEC is Lowest Observed Effect Concentration.

We propose to determine the Phyto Maximum Allowable Concentration by the formula:

PMAC=√(C_contr*〖PhLD〗_5 ) (2)

where Ccontr – background concentration (on the control variant of experiment–without additional metal input);

The PhLD5 is phytotoxic dose 5% (PhLD5) caused reduction of 5% of initial weight (height, length of root etc.).

In our opinion, 5% reduction of initial weight (height, length of root etc.) is the minimal effect, which is similar to the LOEC shows the preliminary changes in the productivity of the plant population. Moreover, the level of significance of deviations, which are considered sufficient for ecological and biological research at the level of 5% (p <0.05) was chosen. The algorithm of obtaining the PhLD5 was represented in previous papers Ryzhenko [22]. Table 2 shows the values of PhLD5 and PMAC for all investigated metals, as well as the background concentration in soil (0-20 centimeters). PMAC was obtained with the help of equation 2. The PMAC for Cd in sod podzolic soil was calculated in this way:

The lowest value of the PMAC had Cd, the highest value of the PMAC had Zn in two studied soils. The chornozem soil ad higher values of the PMAC than Sod podzolic soil. It could be explained by higher content of organic matter, granulometric composition of soil and other properties of chornozem soil. According to the value of PMAC, the metals can be ranked in the following descending order: Zn>Сo>Cu>Ni>Pb>Cd. The PMAC could be used as an environmental standard that regulate the safe level of pollutants in the soil for plant [23-25].

Conclusion

As a result of this investigation, it was proposed to use the Phyto Maximum Allowable Concentration as a permissible level for plants in soil in the polluted ecosystem. The algorithm of calculation of Phyto Maximum Allowable Concentration based on the approach of the existing calculation of Maximum Allowable Toxic Concentration (MATC). The Phyto Maximum Allowable Concentrations were obtained for Hordeum vulgare L. for all researched metals in two soils (mg kg-1;1 N HCl): Cd–1.21; Cu – 7.60; Co–9.77; Zn – 30.77; Ni – 7.40; Pb – 7.48 (sod podzolic sandy loam on layered glacial sands), and Cd – 1.46; Cu – 13.10; Co–13.61; Zn– 44.90; Ni – 12.69; Pb –9,20 calcareous deep chernozem on loamy loess). The Phyto Maximum Allowable Concentration gives the possibility to set the permissible level of metal in soil for plant as a biological organism, but not from the point of view of hygienic regulation. The using of concept of Phyto Maximum Allowable Concentration may be suitable for receiving a permissible level of metals in different soils for other plants in polluted ecosystems. Phyto Maximum Allowable Concentration gives the possibility to estimate the danger of metals directly for plants as a biological object that playing a very important role in the life of ecosystem.

https://lupinepublishers.com/chemistry-journal/pdf/AOICS.MS.ID.000170.pdf

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Lupine Publishers | Synthesis and Antitubercular Acitivity of New Imidazo [2,1-B] [1,3,4] Thiadiazole-Phenothiazine Derivatives

 

Lupine Publishers| An archive of organic and inorganic chemical sciences

Abstract

Keywords:Thiadiazole; Phenothiazine; Thiadiazole; Antitubercular Activity

Introduction

 

Materials and Methods

Synthesis of 5-Phenyl- [1,3,4] thiadiazol-2-ylamine

Equimolar mixture of thiosemicarbazide (0.004 mole) and benzoic acid (0.004mole) in presence of H₂SO₄ in dry ethanol (25ml) was refluxed on a water bath for about 2hrs TLC was used to check reaction progress, then mixture was removed and poured in crushed ice to get a white precipitate, compound 1. A solid product was obtained which was purified over a silica gel column using chloroform: methanol (8:2 v/v) mixture as eluant. The elute was concentrated to get a solid product which was recrystallized from ethanol to yielded compound 1: White crystalline solid. M.P. 223- 225 0C,Yield 70%, IR( ν max cm-1): 1430 (ν_C-C), 1070 (νC-N) 763 (ν_C-S), 1454 (ν_C=C), 1585 (ν_N=C), 3378 (ν_-NH2), 1H NMR: δ(ppm) 4.87 (2H, s, NH2) , 7.29 -7.73 (5H, m, Ar-H), 13C NMR : δ (ppm)126.9-131.01(C of aromatic ring), 169.4,163.8(C2,C5 of thiadiazole ring), Anal. Calcd. for C8H7N3S:C, 54.22, H, 3.98, N, 23.71% found C, 54.09, H, 3.70, N, 23.40%; MS 177.03 (M+).

The compounds 1a-1i were synthesized by the similar method as reported earlier.

a) 5-(2-chloro-phenyl)-[1,3,4]thiadiazole-2-ylamine: M.P.229-2300C, Yield 72%, IR( ν max cm-1): 1433(ν_C-C), 1072 (νCN ), 780 (ν_C-S),1541(ν_C=C), 1587 (ν_N=C), 745 (ν_C-Cl) 3380 (ν_-NH2), 1H NMR δ(ppm) 4.73(2H, s, NH2)7.27-8.18 (4H, m, Ar-H), 13C NMR: δ(ppm) 127.5-133.1(C of aromatic ring),163.3,169.4(C2C5 of thiadiazole ring), Anal. Calcd. for C8H6 ClN3S: C, 45.39, H, 2.86, N,19.85% found C,45.09, H, 2.70, N,19.40%; MS 211.01 (M+)

b) 5-(3-chloro-phenyl)-[1,3,4]thiadiazole-2-ylamine: M.P.228-2300C, Yield 69%, IR( ν max cm-1): 1429 (ν_C-C), 1069 (νC-N), 779 (ν_C-S), 1537(ν_C=C), 1587 (ν_N=C), 737 (ν_C-Cl) 3382 (ν_-NH2), 1HNMR: δ(ppm) 4.75 (2H, s, NH2), 7.35-7.68 (4H, m, Ar-H),13C NMR : δ (ppm) 126.91-31.01 (C of aromatic ring),169.2,162.9(C2C5 of thiadiazole ring), Anal. Calcd. for C8H6 ClN3S: C,45.39, H, 2.86, N, 19.85 % found C, 45.19, H, 2.65, N, 19.49%; MS 211.0 (M+)

c) 5-(4-chloro-phenyl)-[1,3,4]thiadiazole-2-ylamine: M.P.230-2320C,Yield73%, IR( ν max cm-1): 1427 (ν_C-C), 1050 (νCN ), 781 (ν_C-S), 1539 (ν_C=C), 1588 (ν_N=C), 749 (ν_C-Cl),3383 (ν_-NH2), 1HMNR: δ(ppm) 4.89 (2H, s, NH2), 7.73-7.85 (4H, m, Ar-H), 13C NMR: δ (ppm) 129.1-135.6 (C of aromatic ring), 163.4,168.8( C2C5 of thiadiazole ring), Anal. Calcd. for C8H6 ClN3S: C,45.39, H, 2.86, N, 19.85% found C, 45.19, H,2.61, N, 19.38%; MS 211.02 (M+)

d) 5-(2-bromo-phenyl)-[1,3,4]thiadiazole-2-ylamine: M.P.228-2300C,Yield 68%, IR ( ν max cm-1): 1426 (ν_C-C),1055 (νC-N), 768 (ν_C-S), 1545 (ν_C=C), 1640 (ν_N=C), 545 (νC-Br) 3386 (ν- NH2), 1HNMR: δ(ppm) 4.80 (2H, s, NH2) 7.25-7.89 (4H, m, Ar- H), 13C NMR : δ (ppm) 163.1,169.5( C2 C5 of thiadiazole ring), 120.7- 132.1(C of aromatic ring), Anal. Calcd. for C8H6BrN3S: C, 37.52, H, 2.36, N, 16.41% found C, 37.18, H, 2.21, N, 16.35%; MS 254.94 (M+).

e) 5-(3-bromo-phenyl)-[1,3,4]thiadiazole-2-ylamine: M.P. 229-2300C, Yield 67%, IR ( ν max cm-1): 1431 (ν_C-C), 1052 (νC-N), 767 (ν_C-S), 1540 (ν_C=C), 1646 (ν_N=C), 536 (νC-Br), 3388 (ν_-NH2), 1H NMR: δ(ppm) 4.84 (2H, s, NH2), 7.31-7.64 (4H, m, Hz, Ar-H), 13C NMR: δ (ppm): 118.1-132.9(C of aromatic ring),164.08,168.9(C2 C5 of thiadiazole ring), Anal. Calcd. for C8H6BrN3S: C, 37.52, H, 2.36, N, 16.41% found C, 37.28, H, 2.24, N, 16.25%; MS 254.82 (M+).

f) 5-(4-bromo-phenyl)-[1,3,4]thiadiazole-2-ylamine: M.P. 231-233 0C, Yield 69%, IR (ν max cm-1): 1429 (ν_C-C), 1041 (νC-N), 766 (ν_C-S), 1543 (ν_C=C), 1642 (ν_N=C), 541(νC-Br), 3390 (ν- NH2), 1H NMR: δ(ppm) 4.79(2H, s, NH2) ,7.68-7.79(4H, m, Ar-H), 13C NMR :δ (ppm) 124.0-131.0 (C of aromatic ring), 164.1- 169.5(C2 C5 of thiadiazole ring), Anal. Calcd. for C8H6BrN3S: C, 37.52, H, 2.36, N, 16.41% found C, 37.24, H, 2.20, N, 16.35%; MS 254 .86(M+).

g) 5-(2-nitro-phenyl)-[1,3,4]thiadiazole-2-ylamine: M.P. 257-2590C, Yield 78%, IR (ν max cm-1): 1428 (ν_C-C), 1053 (νC-N), 778 (ν_C-S), 1515 (ν_C=C), 1651 (ν_N=C), 1341(ν_C-NO2), 3391 (-νNH2), 1H NMR: δ(ppm) 4.90 (2H, s, NH2), 7.59-8.27 (4H, m, Ar- H), 13C NMR : δ (ppm) 127.5-148.3(C of aromatic ring), 164.01, 169.6(C2C5 of thiadiazole ring), Anal. Calcd. for C₈H₆N₄O_{2S: C, 43.24, H, 2.72, N, 25.21% found C,43.14, H, 2.52, N, 25.8%; MS 222.02 (M+).}

h) 5-(3-nitro-phenyl)-[1,3,4]thiadiazole-2-ylamine: M.P. 259-2610C, Yield 80%, IR: (ν max cm-1): 1426 (ν_C-C), 1048 (νC-N), 776 (ν_C-S), 1527 (ν_C=C), 1656 (ν_N=C), 1343 (ν_C-NO2), 3393 (-νNH2),1H NMR: δ(ppm) 4.78 (2H, s, NH2), 7.59-7.91 (4H, m, Ar- H),13CNMR: δ (ppm) 116.3-140.4 (C of aromatic ring), 164.2 169.3 (C2 C5 of thiadiazole ring), Anal. Calcd. for C₈H₆N₄O_{2S: C, 43.24, H, 2.72, N, 25.21% found C, 43.16, H, 2.62, N, 25.10%; MS 222.22 (M+).}

i) 5-(4-nitro-phenyl)-[1,3,4]thiadiazole-2-ylamine: M.P. 258-2600C, Yield 79%, IR(ν max cm-1): 1432 (ν_C-C), 1055(νCN ), 771 (ν_C-S), 1522 (ν_C=C), 1655 (ν_N=C), 1340 (ν_C-NO2), 3395 (ν_-NH2), 1H NMR: δ(ppm) 4.81(2H, s, NH2) , 7.71-8.27 (4H, m, Ar-H), 13C NMR: δ (ppm)117.2-140.4( C of aromatic ring), 164.2-168.8 (C2C5 of thiadiazole ring), Anal. Calcd. for C₈H₆N₄O_{2S: C, 43.24, H, 2.72, N, 25.21% found C, 43.26, H, 2.60, N, 25.12%; MS 222.19 (M+).}

Synthesis of 2-Chloro-1-phenothiazin-10-yl-ethanone

Chloroacetyl chloride (0.06 mol) was added drop wise at 0.5 0C to phenothiazine (0.06 mol) in dry benzene (100 ml) and the mixture was stirred for 2 hrs. Reaction progress was checked by TLC during the reaction. After the completion of the reaction, the benzene was distilled off to get a solid product washed with petroleum ether which was purified over a silica gel column using chloroform: methanol (8:2 v/v) mixture as eluant. The elute was concentrated to give a product which was recrystallized from ethanol to yielded compound 2. M.P.190-1920C, Yield 94%, IR: (ν max cm-1) 1470 (ν_C-C), 2936 (ν C-H), 1333(ν_N-C),1552 (ν_C=C), 2836 (ν-CH2),1671(νC=O), 685 (ν C-S-C),735(ν C-Cl). 1H NMR: δ(ppm) 4.35(2H, s acyclic CH2), 7.14-7.40 (8H, m, Ar-H),13C NMR δ (ppm) 123.1-138.8 (C of phenothiazine ring), 165.5(C=O acyclic), 42.2 (CH2 acyclic), Anal. Calcd. for C14H10ClNOS: C, 60.98; H, 3.66, N, 5.08, found C, 60.76, H, 3.50, N, 5.01, MS 275.02 (M+).

10-(2-Phenyl-imidazo[2,1-b] [1,3,4] thiadiazol-6-yl)- 10H-phenothiazine

Equimolar amount of 5-Phenyl- [1,3,4] thiadiazol-2-ylamine, compound 1 (0.004 Mole) and Chloro-1-phenothiazin-10-ylethanone, compound 2 (0.004mol) in ethanol (20ml) was refluxed on a water bath for about 18 hr. After the completion of the reaction, the methanol was distilled off to get a solid product which was purified over a silica gel column using chloroform: methanol (8:2 v/v) mixture as eluant. The elute was concentrated to give a product which was recrystallized from ethanol to yielded compound 3. Light green shinny crystalline solid. Light green crystalline solid, M.P. 210- 2120C, Yield 70%, IR: (ν max cm-1) 1481 (ν_C-C), 3171(ν_C-H),1638(νC=N thiadiazole),1589(νC=N imidazole),1286(ν_N-C),772(ν_C-S),1495 (ν_C=C), 681 (ν_C-S-C phenothiazine). 1H NMR:δ(ppm) 6.77(1H, s, imidazole),7.1-7.4 (8H, m, Ar-H phenothiazine),7.45-7.46 (3H, m Ar-H thiadiazole),8.00(2H, d, J = 8.0, Hz, Ar-H), 13C NMR: δ(ppm) 125.9-130.4(C of aromatic ring), 124.2, 144.0 and 116.6-128.1(C of phenothiazine), 175.2,164.4 (C2,C5 thiadiazole), 100.9 and 150.6(C of imidazole), Anal. Calcd. for C22 H14 N4 S2: C, 61.03, H, 3.03, N, 12.94 %, found C, 61.00, H,3.01, N, 12.74%; MS 398.06 (M+).

The compounds 3a-3i were synthesized by the similar method as reported earlier

a. 10-[2-(2-Chloro-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol- 6-yl]-10H-phenothiazine: M.P. 209-211 0C,Yield 71%, IR: (νmax cm-1)1479 (ν_C-C), 3172(ν_C-H), 1640 (νC=N thiadiazole), 1597(νC=N imidazole),1280(ν_N-C), 772(ν_C-S), 741(ν_C-Cl), 1493(ν_C=C),682(ν_C-S-C phenothiazine). 1H NMR: δ(ppm)6.71(1H, s, imidazole), 7.11-7.45 (8H, m, Ar-H phenothiazine), 7.40- 7.76 (4H, m, Ar-H aromatic ring),13C NMR:δ (ppm) 127.6- 133.2 (C of aromatic ring), 124.4,144.2 and 116.7-129.3 (C of phenothiazine),164.7,156.3 (C2,C5 thiadiazole), 100.8 and 150.4 (C of imidazole), Anal. Calcd. for C22H13Cl N4 S2, C, 61.03, H, 3.03, N,12.94%, found C, 61.00, H, 3.01, N, 12.74%; MS 432.03(M+).

b. 10-[2-(3-Chloro-phenyl)-imidazo[2,1-b][1,3,4] thiadiazol-6-yl]-10H-phenothiazine: M.P. 210-2110C, Yield 72%, IR:(ν max cm-1)1482 (ν_C-C), 3169 (ν_C-H), 1639 (νC=N thiadiazole), 1598 (νC=N imidazole), 1284(ν N-C),77(ν_C-S),737(νCCl ),1491(ν_C=C),679 (ν_C-S-C phenothiazine). 1H NMR: δ(ppm) 6.76(1H, s, imidazole), 7.42-7.71 (3H, m, Ar-H aromatic ring), 7.11-7.44 (8H, m Ar-H penothiazine), 7.95 (1H, t, J = 1.5, 0.4 Hz, Ar-H), 13C NMR: δ (ppm)126.9-131(C of aromatic ring), 124.1,145.1 and 116.6-128.0(C of phenothiazine), 157.7,164.3 (C2,C5 thiadiazole), 100.7 and 150.7 (C of imidazole), Anal. Calcd. for C22H13 ClN4S2: C, 61.03, H, 3.03, N, 12.94%, found C, 61.01, H, 3.00, N, 12.84%; MS 432.02 (M+).

c. 10-[2-(4-Chloro-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol-6- yl]-10H-phenothiazine: M.P. 212-2140C, Yield 70%, IR:(νmax cm-1) 1480 (ν_C-C), 3176 (ν_C-H), 1638 (νC=N thiadiazole), 1589 (νC=N imidazole), 1285 (ν N-C), 770 (ν C-S), 742 (ν C-Cl), 1488 (ν_C=C), 682 (ν C-S-C phenothiazine).1H NMR: δ(ppm) 6.79(1H, s, imidazole),7.68-7.70 (4H, m, Ar-H aromatic ring), 7.12- 7.46 (8H, m Ar-H phenothiazine), 13C NMR : δ (ppm) 127.2- 135.7 (C of aromatic ring), 124.4,145.3 and 116.1-128.3(C of phenothiazine),157.7,156.3 (C2,C5 thiadiazole), 100.6 and 150.3 (C of imidazole), Anal. Calcd. for C22 H13 Cl N4S2:C, 61.03, H ,3.03, N, 12.94%, found C, 61.00, H, 3.02, N, 12.72%; MS 432.05 (M+).

d. 10-[2-(2-Bromo-phenyl)-imidazo[2,1-b][1,3,4] thiadiazol-6-yl]-10H-phenothiazine: M.P. 211-2120C Yield 70%, IR: (νmax cm-1) 1478 (ν_C-C),3175 (ν_C-H),1637(νC=N thiadiazole), 1588(νC=N imidazole), 1279(ν N-C) ,768 (ν_C-S), 542 (νC-Br), 1490 (ν_C=C), 685 (ν C-S-C phenothiazine). 1H NMR: δ(ppm) 6.73(1H, s, imidazole), 7.37-7.77 (4H, m, Ar-H aromatic ring),7.11-7.48 (8H, m Ar-H phenothiazine), 13C NMR: δ (ppm) 120.7-132.1 (C of aromatic ring),124.5,145.5 and 116.5- 128.3(C of phenothiazine),156.2,164.5(C2, C5 thiadiazole), 100.4 and 150.1 (C of imidazole), Anal. Calcd. for C22 H13 Br N4 S2: C, 55.35, H, 2.74, N,11.74%, found C, 55.20, H, 2.52, N, 11.62%, MS 475.96 (M+).

e. 10-[2-(3-Bromo-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol- 6-yl]-10H-phenothiazine: M.P. 213-2140C, Yield 69%, IR:(ν max cm-1)1480(ν_C-C), 3174 (ν_C-H), 1638 (νC=N thiadiazole), 1590(νC=N imidazole),1281(ν_N-C)766 (ν_C-S), 540 (νC-Br) 1491 (ν_C=C), 683(ν_{CS- C} phenothiazine). 1H NMR: δ(ppm) 6.76 (1H, s, imidazole), 7.41-7.61 (3H, m, Ar-H aromatic ring), 7.10-7.49 (8H, m, Ar-H phenothiazine), 7.76 (1H, td, J = 1.5, Hz, Ar-H aromatic ring),13C NMR: δ(ppm)118.7-133.0 (C of aromatic ring), 124.6,145.7 and 116.7-128.4 (C of phenothiazine) , 175.1,164.4 (C2,C5 thiadiazole), 100.1 and 150.2(C of imidazole), Anal. Calcd. for C22 H13 Br N4 S2: C, 55.35%, H, 2.74, N,11.74 found C, 55.20, H, 2.52, N, 11.62%; MS 475.98(M+).

f. 10-[2-(4-Bromo-phenyl)-imidazo[2,1-b][1,3,4] thiadiazol-6-yl]-10H-phenothiazine: M.P. 215-2160C, Yield 68 %, IR:(ν max cm-1)1482 (ν_C-C), 3171 (ν_C-H), 1636 (νC=N thiadiazole), 1594 (νC=N imidazole), 1286 (ν_N-C) 769 (ν_C-S), 538 (νC-Br) 1489 (ν_C=C), 688 (ν_C-S-C phenothiazine), 1H NMR: δ(ppm) 6.72 (1H, s, imidazole), 7.69-7.78 (4H, m, Ar-H aromatic ring), 7.10-7.49 (8H, m Ar-H penothiazine), 13C NMR: δ(ppm)- 124- 131(C of aromatic ring), 124.2,145.8 and 116.8-128.7 (C of phenothiazine), 175.5,164.6 (C2,C5 thiadiazole), 100.3 and 150.7 (C of imidazole), Anal. Calcd. for C22H13BrN4S2: C, 55.35, H, 2.74, N, 11.74% found C, 55.19, H, 2.42, N, 11.72%; MS 475.99 (M+).

g. 10-[2-(2-Nitro-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol- 6-yl]-10H-phenothiazine: M.P. 215-2170C, Yield 74%, IR :(ν max cm-1) 1487 (ν_C-C), 3170 (ν_C-H),1642(νC=N thiadiazole), 1598 (νC=N imidazole), 1287 (ν_N-C), 770 (νC-C), 1343 (ν_C-NO2) 1494 (ν_C=C), 689 (ν_C-S-C phenothiazine), 1H NMR: δ (ppm) 6.73 (1H, s, imidazole), 7.49-8.35 (4H, m, Ar-H aromatic ring), 7.11-7.48 (8H, m Ar-H phenothiazine), 13C NMR : δ (ppm) 127.6-148.4 (C of aromatic ring), 124.7,144.9 and 115.9-127.8( C of phenothiazine), 156.5,164.4 (C2,C5 thiadiazole), 100.2 and 150.6 (C of imidazole), Anal. Calcd. for C₂₂H₁₃N₅O₂S₂: C, 59.58, H, 2.95, N, 15.79%, found C, 59.38, H, 2.85, N,15.59 %; MS 443.05 (M+).

h. 10-[2-(3-Nitro-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol- 6-yl]-10H-phenothiazine (3h): M.P. 216-2180C, Yield 75 %,IR: (νmax cm-1)(ν_C-C) 1483, (ν_C-H) 3172, 1641 (νC=N thiadiazole), 1596 (νC=N imidazole), 1286 (ν_N-C), 773 (ν_C-S), 1340 (ν_C-NO2) ,1492 (ν_C=C), 685 (ν_C-S-C phenothiazine), 1H NMR: δ (ppm) 6.68 (1H, s, imidazole), 7.58-8.84 (4H, m, Ar-H aromatic ring), 7.10- 7.49 (8H, m Ar-H phenothiazine), 13C NMR : δ (ppm) 116.4- 140.5(C of aromatic ring), 124.8, 145.9 and 115.8-128.5(C of phenothiazine), 175.7,164.6 (C2,C5 thiadiazole), 100.1 and 150.9 C of imidazole, Anal. Calcd. for C₂₂H₁₃N₅O₂S₂: C, 59.58, H, 2.95, N, 15.79 found C, 59.40, H, 2.81, N, 15.55; MS 443.04 (M+).

i. 10-[2-(4-Nitro-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol- 6-yl]-10H-phenothiazine: M.P.220-2220C,Yield 76%, IR: (νmax cm-1) 1480 (ν_C-C), 3170 (ν_C-H), 1638 (νC=N thiadiazole), 1592 (νC=N imidazole), 1285 (ν_N-C), 770 (ν_C-S),1338 (ν_C-NO2), 1491 (ν_C=C), 685 (ν_C-S-C phenothiazine), 1H NMR: δ (ppm) 6.72 (1H, s, imidazole), 7.80-8.33 (4H, m, Ar-H aromatic ring), 7.11- 7.49 (8H, m Ar-H phenothiazine), 13C NMR : δ(ppm) 117.3- 140.5( C of aromatic ring), 124.9,145.6 and 116.8-128 (C of phenothiazine),175.1,163.4 (C2,C5 thiadiazole),100.5 and 150.8 (C of imidazole), Anal. Calcd. for C₂₂H₁₃N₅O₂S₂: C, 59.58, H, 2.95, N,15.79%, found C, 59.37, H, 2.81, N, 15.59%; MS 443.02 (M+).

Antitubercular activity

The above synthesized compounds were screened against M. tuberculosis (H37Rv strain) using Lowenstein-Jensen (L.J.) Agar method at 50 and 100 μg/mL concentrations. The results were showing in Table 1. The standard antitubercular drugs isoniazid was taken as standards, showed 100% activity at both the above concentrations. The minimum inhibitory concentration (MIC) values of the synthesized compounds were determined.

Conclusion

In the conclusion we were successful in the initial hypothesis of synthesizing broad-spectrum antibiotics through experimentation. We report a successful effort to combine pharmacophoric groups; 5-Phenyl- [1,3,4] thiadiazol-2-ylamine and Chloro-1-phenothiazin- 10-yl-ethanone and the compounds were synthesised in good yield. The structures of compounds were established by FT-IR, 1H NMR, 13CNMR and Mass spectrometry techniques. The synthesized compounds posses antitubercular activity against Mycobacterium tuberculosis H37Rv strain.

 

 

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