(1)T R In REATM Fulfillme D Depart ndian In MENT O W A Sub ent of the D OCTOR Ardhe Un Dr

Mr. ARDHENDU SEKAR GIRI

Golder, "Oxidative degradation of Dipyrone from afvalwater using Fenton reagent", Indian Chemical Engineering Congress (CHEMCON th Desember, 2012, Dr. Golder, "Degradation of Dipyrone in water by heterogeneous photo catalytic reaction: Degradation mechanism and reaction pathways", aangebied in Reflux-1.0 in Chemiese Ingenieurswese Departement, 27-29 Maart, 2013, IIT Guwahati, Assam, Indië.

Intro

O Pharma

HAPT

TER 1

Survey

Environmental impact of pharmaceuticals waste

Low levels of PhAC have been detected in surface, ground, and drinking water sources, in addition to wastewater, worldwide (Kolpin et al., 2002). Therefore, it is possible that PhACs may affect aquatic and terrestrial organisms (Adams et al., 2002).

Sources of PhACs in water and wastewater

Unregulated disposal of unused and expired drugs is the primary input of PhACs to the environment from hospitals and healthcare facilities (Chang et al., 2010). Surface water and groundwater: Residues of pharmaceutical products can enter the aquatic environment due to incomplete removal in WWTPs (Goutama et al., 2007).

Table 1.2. Concentrations of pharmaceuticals in water and solid wastes (Stasinakis et al., 2008)

Present Indian scenario: Pharmaceutical wastewater pollution

Almost all companies indiscriminately dump waste on nearby land and water bodies. There are thousands of pharmaceutical industries across the country that dump millions of gallons of untreated wastewater each time.

Techniques for Treatment of Pharmaceutical Wastewater .1 Adsorption technique

• Membranes processes
• Biological treatment
• Advanced oxidation processes (AOPs)

In the presence of UV radiation, iron ions (Fe3+) are also photocatalytically converted into ferrous ions (Fe2+) forming additional HO radicals (Equation 1.5) (Moraes et al., 2004). The UV radiation required for the photolysis of H2O2 is not available in the solar spectrum (Haddad et al., 2014).

Table 1.4. Performance of traditional techniques for treatment of pharmaceutical effluents

Advantages and Limitations of AOPs

• Treatment of Pharmaceutical Wastewater using AOPs: Literature Survey
• Knowledge gap and Objectives of the work

To determine the concentration of hydroxyl radical (HO.) and to develop the kinetic model of drug and degradation product degradation. K., "Oxidative degradation of diuron herbicide in aquatic environment by advanced oxidation processes based on Fenton reaction", Chem.

Table 1.5. Fenton process (FP) for removal of PhACs.

C HAPTER 2

Materials and Methods

• Chemicals and Reagents
• AR 144-55-8 Sodium nitrate (NaNO 3 ) 99 AR 7631-99-4
• AR 7783-85-9 Formaldehyde (HCHO) 37-41 AR 50-00-0
• AR 10034-99-8 Molybdenum trioxide (MoO 3 ) GR 5758
• Analytical Methods
• High Performance Liquid Chromatography (HPLC) for concentration determination of drug and iron-CHPL complex
• TOC determination
• Measurement of COD
• Derivatization procedure and determination of HO • concentration
• Liquid chromatography-mass spectrometry (LC-MS)
• Determination of inorganic ions
• FTIR spectroscopic analysis
• UV-Vis spectroscopy
• Antimicrobial activity test
• Experimental procedure

In the case of CHPL, CIP and DIPY mixture (CCD), methanol and water (70:30 v/v) at a flow rate of 0.4 mL/min was used as the mobile phase and scanning was performed at a wavelength of 236 nm. . The acidified sample (pH ≤ 2) was dissolved with a stream of N2 since bicarbonates in the sample dissolve in CO2. A second digestion vessel with the same amount of these reagents and DI water in place of the sample was used as a blank.

DI water was used to prepare the dilution water and this was aerated to oxygenate it before use. The sample was subjected to an additional filtration step using 0.45μm cellulose filter (manufacture: Pall India Pvt. UV/TiO2 Photocatalysis (UVPC): Rutile-type crystal TiO2 was used to decompose DIPY.

Figure 2.1. Chemical structure of chosen pharmaceuticals. (a) Chloramphenicol [2,2- [2,2-dichloro-N-((1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl) acetamide], (b) Ciprofloxacin [1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-

C HAPTER 3

Results and Discussion .1 Formation of FeCHPLCOM

• CHPL and FeCHPLCOM degradation in FP, PFP and UVP
• Degradation pathways of CHPL
• Antimicrobial activity of CHPL and its decomposition products Figure 3.21 shows the toxicity of CHPL and its degradation products towards E. coli in

The absorption spectra of CHPL and FeCHPLCOM showed three necessary maximum peaks (λmax) at 213, 263 and 389 nm (Figure 3.1). The faster CHPL and TOC removal can also be confirmed from the residual concentration of H2O2 and Fe2+. H2O2 was added after 10 minutes of chelation time and the variation of CHPL and FeCHPLCOM concentrations is shown in Figure 3.11.

Chromatogram of CHPL and FeCHPLCOM remaining found in FP and PFP at 10 minutes of reaction. CHPL degradation mechanisms are proposed and supported by fragments obtained in mass spectra. The proposed mechanism implies that most of the intermediates were formed by the degradation of the side chain of the CHPL molecule.

Figure 3.2. Chromatogram of pure CHPL and Fe 2+ -CHPL mixture at different Fe 2+

C HAPTER 4

Ciprofloxacin Degradation: Kinetic Modelling, Reaction Pathways and Toxicity Assay

Introduction

Most studies assume that HO• formation and disappearance rates are instantaneous (Mantzavinos et al., 1996). HO• can be measured by the concentration of hydroxylated products formed with aromatic compounds such as phenol, benzoic acid and salicylic acid (Gulkaya et al., 2006). Problems associated with the determination of HO• in AOP include: (i) multiple reactions, (ii) secondary generation of superoxide, (iii) adduct with limited solubility, and, (iv) iron complex formation (+2, + 3)- salicylic acid that inhibits the formation of HO• in Fenton and Fenton-like reactions (Kang et al., 2002).

To overcome these limitations, dimethyl sulfoxide (DMSO) as the chemical probe can be used for HO• determination. DMSO is highly water soluble and can trap most hydroxyl radicals (HO•) formed in AOPs. An oxidative kinetic equation involving HO• for [CIP] as well as for degradation products [DPs] was developed.

Determination of Mean Oxidation Number of Carbon (MONC)

The mechanism of CIP oxidation is proposed and supported by the results obtained in the LC-MS spectra. Studies of the antimicrobial activity of CIP and its degradation products were also carried out.

1.5 COD

• Kinetic Model Development
• Results and Discussion .1 Optimal Fe 2+ /H 2 O 2 molar ratio
• Optimal pH in FP
• Variation of MONC with reaction time
• Proposed mechanisms of CIP degradation
• Kinetic model for the oxidation of CIP and degradation products
• Antimicrobial activity of CIP and its decomposition products
• Major Findings

The removal of CIP, COD and TOC per unit HO consumption is shown in Figures 4.4 to 4.6. It clearly implies that HO* was mainly consumed for the fragmentation of daughter ions compared to CIP cleavage. The increased initial rate of HO formation resulted in a higher initial rate of removal of CIP (up to 5 min), COD (up to 15 min), and TOC (up to 15 min).

In general, the loss of carboxyl unit ([M+H- . 44]+) and fluoride ([M+H-22]+), are the typical fragmentation pathways of fluoroquinolone (Klauson et al., 2010). The appearance of such fragmentations in the MSn spectra gives some hints for the subtraction of different moieties based on their mass losses such as 44 for - COOH group. The variation of MONC also gives the hint for the successive oxidation of CIP molecule. Therefore, a better estimate of initial HO• radical concentration (COH0 ) and the second order rate constant of CIP oxidation can be made.

Figure 4.1. Chemical structure of CIP drug [1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1- [1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-Quinoline-3-carboxylic acid]

C HAPTER 5

Dipyrone Degradation: Mineralization, Reaction Pathways, Biodegradability and Toxicity Assay

Results and Discussion

• Optimal Fe 2+ concentration for 4-MAA degradation in FP
• pH dependent 4-MAA cleavage
• Influence of TiO 2 on 4-MAA decomposition in UVPC
• Biodegradability and antimicrobial activity of 4-MAA and its degradation products

Therefore, the reaction occurs in a diffusion-controlled regime in the case of UVPC (Petrovic et al., 2011). The slow second stage is associated with the opening and mineralization of the pyrazolinone ring (Gomez et al., 2007). Fe(III)-chelate complexes are more stable in FP due to less possibility of further degradation (Knight et al., 1975).

It indicates the formation of an iron-chelate complex, which is unstable under UV light (Zepp et al., 1992). The HO• radical can easily attack the N1 position of the pyrazolinone ring in the presence of a partially empty p-orbital of the N-atom (Sykes et al., 2005). It has a greater tendency to transform into the quinone form (Leonidas et al., 2007), i.e. formation of compound D25, obtained in both FP and UVP, which has positive properties of the benzene nucleus.

Figure 5.2. Effect of Fe 2+ concentration on removal of 4-MAA in FP. Experimental conditions: [4-MAA] 0 = 50 mg/L, H 2 O 2 = 20 mM, pH = 3.5 and temperature 25°C

Major Findings

A., "Kinetic Model for Advanced Oxidation Processes of Aromatic Hydrocarbons in Water: Application to Phenanthrene and Nitrobenzene", Ind. Pilot survey for the monitoring of pharmaceuticals and related compounds in a wastewater treatment plant located on the Mediterranean coast, "Chemisphera. R., "Degradation of dipyrone and its key intermediates by solar AOPs Identification of intermediate products and toxicity assessment", Catal.

R and Ghavami, M., "Taguchi Experimental Design Used for Nano-Photocatalytic Degradation of the Pharmaceutical Drug Aspirin," J. Tekin, H., Bilkay, O., Selale, S., and Tolga, H ., "Use of Fenton oxidation to improve the biodegradability of a pharmaceutical wastewater," J.

C HAPTER 6

Mixed Drug Decomposition: Comparison to Individual Drug Mineralization, Evolution of

Introduction

• Drugs removal and mineralization
• Effect of foreign anions
• Degradation pathways and formation of inorganic ions
• Antimicrobial activity of drug mixture and its decomposition products

The separate addition of HCO3 and NO3 reduced the degradation rate of five out of six PhACs in the UV/H2O2 process (Yuan et al., 2013). However, Cl- did not show any specific impact on the dissolution even because Cl- acts as an HO scavenger and it could also generate chlorine atom (Cl-) and dichloride anion radicals (Cl2--) (Anipsitakis et al., 2006). ). 2001) reported that the degradation efficiency of n-chlorobutane (BuCl) was hampered by the production of common ions such as NH4+, NO3-, HCO3- and CO32- and low molecular weight intermediates (Segura et al., 2012).

Park et al., (2008) reported an inhibitory effect of NO2- on the degradation of volatile organic carbon (VOC) during photolysis. It can be roughly said that the formation of higher molecular weight intermediates occurred more in CCD mixtures than separately (Trovo et al., 2013; Section 3.1 of Chapter 3, Section 4.4.5 of Chapter 4 and Section 5.2.5 of Chapter 5), probably due to enhanced chelation and polymerization. The neucleophilicity of both centers increases due to the presence of an amide group in the C2 center (Csay et al., 2012; Finar et al., 2001).

Table 6.1. Concentration and organic loading of pharmaceutical effluents.

Major Findings

D., "The effect of nitro substitution on the photochemistry of benzyl benzohydroxamate: photoinduced release of benzohydroxamic acid", J.L., "UV and solar-based photocatalytic degradation of organic pollutants by nano-sized TiO2 grown on carbon nanotubes", Catal. B., "Effects of nitrate on the UV photolysis of H2O2 for VOC degradation in an aqueous solution", Environ.

Degradation of the antibiotic chloramphenicol by the photo-Fenton process at laboratory scale and solar pilot plant: Kinetic evaluation, toxicity and inactivation”, Solar Energy.

C HAPTER 7

Conclusions, Limitations and Future Recommendations

Overall Conclusions

Most of the intermediates were formed by degradation of the side chain of the CHPL molecule, and the aliphatic amide chain was cleaved by HO• attack at the C2 center. Four primary daughter ions were generated after CIP cleavage and MONC increased from 1.27 to 2.1 at the optimal treatment condition. The proposed second-order kinetic model for the breakdown of both CIP and degradation products (DP) exhibited excellent agreement with the experimental data.

The proposed mechanism implies that most of the intermediates originated from the degradation of the pyrazolinone ring. A slightly lower mineralization efficiency of CHPL, CIP and DIPY was observed in an equimolar CCD mixture compared to individual drug degradation. Cl- and F- were formed during the degradation of CHPL and CIP, and their addition inhibited the degradation efficiency of CHPL and CIP by approximately 11.9 and 12.4%, respectively.

Limitations of the Work

Golder, "Fenton, Photo-Fenton, H2O2-photolysis and TiO2 photo-catalysis for Dipyrone oxidation: Drug removal, mineralization, biodegradability and degradation mechanism", Ind. Golder, "Ciprofloxacin degradation from aqueous solution by Fenton oxidation: Reaction kinetics and degradation mechanisms", RSC Adv. Golder, "Degradation of pharmaceutical from waste water: Oxidative Fenton process", Chemical Engineering Congress (CHEMCON th Fenton process), Chemical Engineering Congress (CHEMCON th December, 2011, Bangalore, India.

Golder, "Fenton oxidation process for the removal of an antimicrobial drug from wastewater", 2nd International Conference on Advanced Oxidation drug from wastewater", 2nd International Conference on Advanced Oxidation Processes (AOP 2012), October 5-8, 2012, Kottayam, Kerala . Golder, "Oxidative degradation of dipyrone from wastewater using Fenton reagent", Indian Chemical Engineering Congress (CHEMCON th Fenton reagent), Indian Chemical Engineering Congress (CHEMCON th December, 2012, Dr. Golder, "Mechanism and identification of reaction by-products for the degradation) of Chloramphenicol drug in heterogeneous photo-catalytic Process", degradation of Chloramphenicol drug in heterogeneous photo-catalytic Process", International Conference on Chemical and Bioprocess Engineering (ICCBPE th. November, 2013, National Institute of Technology Warangal, Andhra Pradesh, India.