study of semiconductor photocatalysed oxidation of

www.wjpps.com Vol 9, Issue 3, 2020.

1057

Meena. World Journal of Pharmacy and Pharmaceutical Sciences

STUDY OF SEMICONDUCTOR PHOTOCATALYSED OXIDATION OF

Γ-HYDROXYBUTYRIC ACID (GAMMA HBA) USED AS ILLEGAL

DRUG AND PHARMACEUTICAL INDUSTRIES

*Dr. Pushkar Raj Meena

*H.O.D. Chemistry, S.P.S.B. Govt. College-Shahpura, Bhilwara (Raj.)-India.

ABSTRACT

In the last century, scientists have made rapid and significant advances

in the field of semiconductor physics. In 1972, Fujishima and Honda

discovered the photocatalytic water splitting effect on TiO2.[1]

Since

then, many research efforts have been performed in understanding the

fundamental processes and in enhancing the photocatalytic efficiency

of TiO2.[2]

Semiconducting materials have been the subject of great

interest due to their numerous practical applications, and they provide

fundamental insights into the electronic processes involved.[3]

The

presence of pharmaceuticals and personal care products (PPCPs) in

surface water is an emerging environmental issue and provides a new challenge to drinking

water, wastewater, and water reuse treatment system.[5]

As a food additive[7-9]

, TiO2 (titanium

dioxide) is approved for use in various countries like EU, USA, Australia and New Zealand;

it is listed by INS number 270 or E number E-270. Gamma Hydroxybutyric acid is an illegal

and dangerous drug and banned by various countries word wide and it can be easily

manufactured with very little knowledge of chemistry. GHB is primarily known to the

general public as a date rape drug. GHB has been used in cases of drug-related sexual assault,

usually when the victim is vulnerable due to intoxication with a sedative, generally

alcohol,[14]

while available as a prescription for rare and severe forms of sleep disorder such

as narcolepsy in some other countries, notably most of Europe, GHB was banned in the U.S.

by the FDA in 1990. GHB is a central nervous system depressant used as an

intoxicant,[18]

although it produces a stimulant effect at lower doses due to its action on the

GHB receptor. It has many street names, including G, Liquid G, Liquid X, Liquid E,[19]

Georgia Home Boy, Juice, Mils, and Fantasy. Many remarkable organic methodologies were

developed in the last century, but toxic properties of many reagents and solvents were not

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 9, Issue 3, 1057-1071 Research Article ISSN 2278 – 4357

*Corresponding Author

Dr. Pushkar Raj Meena

H.O.D. Chemistry, S.P.S.B.

Govt. College-Shahpura,

Bhilwara (Raj.)-India.

Article Received on

06 Jan. 2020,

Revised on 26 Jan. 2020,

Accepted on 16 Feb. 2020

DOI: 10.20959/wjpps20203-15374


1058


known. It is therefore planed to investigate photo- oxidation of γ-hydroxybutyric acid by

semiconductors.

KEYWORDS: Gamma hydroxybutyric acid, titanium dioxide, photocatalysis, illegle drug.

INTRODUCTION

In the last century, scientists have made rapid and significant advances in the field of

semiconductor physics. In 1972, Fujishima and Honda discovered the photocatalytic water

splitting effect on TiO2.[1]

Since then, many research efforts have been performed in

understanding the fundamental processes and in enhancing the photocatalytic efficiency of

TiO2.[2]

Semiconducting materials have been the subject of great interest due to their

numerous practical applications, and they provide fundamental insights into the electronic

processes involved.[3]

Photocatalysis has become an intensively researched field due to practical interest in air and

water remediation, self-cleaning surfaces, self sterilizing surfaces, and hydrogen generation

using the green energy of sunlight. Many oxide semiconductors show practical performance

as photocatalysts in water disinfection and detoxification. The most studied photocatalyst,

Titania, is still being actively researched and has become quite well understood

experimentally and theoretically.[4]

The presence of pharmaceuticals and personal care products (PPCPs) in surface water is an

emerging environmental issue and provides a new challenge to drinking water, wastewater,

and water reuse treatment system.[5]

One class of antibiotics pharmaceuticals, sulfa drugs, is

frequently found in the environmental waters, such as sewage treatment plants water and

river.[8]

Several recent researches also demonstrated the potential omnipresence of sulfa

pharmaceuticals in the soil environment and manure.[6]

As a food additive[7-9]

, TiO2 (titanium

dioxide) is approved for use in various countries like EU, USA , Australia and New Zealand;

it is listed by INS number 270 or E number E-270.

Gamma Hydroxybutyric acid is an illegal and dangerous drug and banned by various

countries word wide. GHB can be easily manufactured with very little knowledge of

chemistry, as it only involves the mixing of its two precursors, GBL and an alkali

hydroxide, such as NaOH, to form the resulting GHB salt. Due to the ease of manufacture

and the availability of its precursors, it is not mainly produced in illicit laboratories like most


1059


other synthetic drugs. While available as a prescription for rare and severe forms of sleep

disorder such as narcolepsy in some other countries, notably most of Europe, GHB was

banned in the U.S. by the FDA in 1990. However, on 17 July 2002, GHB was approved for

treatment of cataplexy, often associated with narcolepsy. GHB is "colorless and odorless"[10]

in the typical scenario; GHB has been synthesized from γ-butyrolactone (GBL) by adding

NaOH (lye) in ethanol or water. GHB is also produced as a result of fermentation and so is

found in small quantities in some beers and wines, in particular fruit wines. The amount

found in wine is pharmacologically insignificant and not sufficient to produce psychoactive

effects.[11]

Synthesis of the chemical GHB was first reported in 1874 by Alexander

Zaytsev,[12]

but the first major research into its use in humans was conducted in the early

1960s by Dr. Henri Laborit to use in studying the neurotransmitter γ-aminobutyric acid

(GABA). GHB is also produced as a result of fermentation, and is found in small quantities in

some beers and wines, beef and small citrus fruits.[13]

GHB is primarily known to the general public as a date rape drug. GHB has been used in

cases of drug-related sexual assault, usually when the victim is vulnerable due to intoxication

with a sedative, generally alcohol.[14]

A date rape drug, also referred to as a predator drug, is

any drug that is an incapacitating agent which, when administered to another person,

incapacitates the person and renders them vulnerable to a drug facilitated sexual assault

(DFSA), including rape. It is also used illegally as an intoxicant, to try to increase athletic

performance, and as a date rape drug.[15]

Athletes also use GHB, as GHB has been shown to

elevate human growth hormone in vivo.,[16]

one study found that it doubled growth hormone

secretion in normal young males.[17]

GHB is a central nervous system depressant used as an intoxicant,[18]

although it produces a

stimulant effect at lower doses due to its action on the GHB receptor. It has many street

names, including G, Liquid G, Liquid X, Liquid E,[19]

Georgia Home Boy, Juice, Mils,

and Fantasy. At higher doses, GHB may induce nausea, dizziness, drowsiness,

agitation, visual disturbances, depressed breathing, amnesia, unconsciousness, and there are

thousands of cases of death by GHB high doses.

GHB has been used in a medical setting as a general anesthetic and as a treatment for

cataplexy, narcolepsy, and alcoholism.[20,21]

Consuming GHB with alcohol is dangerous as it

can lead to respiratory arrest and vomiting in combination with unrouseable sleep, a

potentially lethal combination.[22,23]

In humans, GHB has been shown to reduce the


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elimination rate of alcohol. This may explain the respiratory arrest that has been reported

after ingestion of both drugs.[24]

It is commonly used in the form of a salt, such as sodium γ-

hydroxybutyrate (Na GHB, sodium oxybate, or Xyrem) or potassium γ-hydroxybutyrate

(K.GHB, potassium oxybate). GHB is the active ingredient in the prescription medication

sodium oxybate (Xyrem). The only common medical use for GHB today are in the treatment

of narcolepsy and more rarely alcoholism.[25]

It is sometimes used off-label for the treatment

of fibromyalgia.[26]

Sodium oxybate is approved by the U.S. Food and Drug Administration

(FDA) for the treatment of cataplexy associated with narcolepsy[26]

and excessive daytime

sleepness (EDS) associated with narcolepsy. GHB has been shown to reliably increase slow-

wave sleep[27]

and decrease the tendency for REM sleep in modified multiple sleep latency

tests.[28]

Succinic semialdehyde dedehydrogenase deficiency is a disease that causes GHB to

accumulate in the blood. As certain succinate salts have been shown to elevate growth

hormone in vitro,[29]

and because GHB is metabolized into succinate some people have

suggested this plays a role in the growth hormone elevations from GHB. Succinic

semialdehyde dehydrogenase deficiency (SSADHD), also known as 4-hydroxybutyric

aciduria or gamma-hydroxybutyric aciduria, is a rare autosomal recessive disorder of the

degradation pathway of the inhibitory neurotransmitter γ-aminobutyric acid, or GABA.

SSADH deficiency is caused by an enzyme deficiency in GABA degradation. Under normal

conditions, SSADH works with the enzyme GABA transaminase to convert GABA

to succinic acid. Succinic acid can then be utilized for energy production via the Krebs cycle.

However, because of the deficiency, the final intermediate of the GABA degradation

pathway, succinic semialdehyde, accumulates and cannot be oxidized to succinic acid and is

therefore reduced to gamma-hydroxybutyric acid (GHB) by gamma-hydroxybutyric

dehydrogenase. This causes elevations in GHB and is believed to be the trademark of this

disorder and cause for the neurological manifestations seen.[30]

SSADH deficiency is

inherited in an autosomal recessive fashion. Such diseases are caused by an error in a single

DNA gene.

Gama-Hydroxybutyric acid has a great biological and pharmaceutical importance as

discussed above and it is one of the members of the series of hydroxyacids undertaken in this

study. In addition; although many remarkable organic methodologies were developed in the


1061


last century, but toxic properties of many reagents and solvents were not known. It is

therefore planed to investigate photo- oxidation of γ-hydroxybutyric acid by semiconductors.

EXPERIMENTAL

The organic compounds of γ -hydroxybutyric acid, Silica gel- G, Resublimed Iodine (sm),

ninhydrin, titanium oxide, tungsten oxide, iron oxide, zinc oxide, cadmium sulphide, stannic

oxide, copper oxide, some other semiconductors and other analytical chemicals are purchased

by SD Fine or E Merck chemical suppliers.

UV chamber with UV tube 30 W (Philips), spectrophotometer (Systronic), spectrometer

(Systronic), tungsten filament lamps 2 x 200 W (Philips) for visible light, 450 W Hg-arc

lamp, water shell to filter out IR radiations and to avoid any thermal reaction, necessary glass

wares, thin layer chromatography and paper chromatography kits for to determine the

progress of reaction, conductivity meter (Systronic) to determine the optimum yields of

photoproducts, magnetic stirrer, pH meter (Eutech pH 510), spectrophotometer (Systronic)

and I.R. spectrometer (Perkin- Elmer Grating-377) was used.

γ -Hydroxybutyric acid solutions are prepared in water and acetonitrile solvent as the

required concentrations as mentioned in the Tables. The required concentration of

semiconductor or mixed semiconductors has been added to the reaction mixture for

heterogeneous photocatalytic reactions. Variations were made to obtain the optimum yield of

photoproducts as the given practical conditions.

The progress of reaction was monitored by running thin layer chromatography at different

time intervals, where silica gel-G was used as an adsorbent. For colorless spot detection a

slide spot detector; UV chamber (Chino’s) was used. At the end of reaction or the process the

photoproducts has been isolated as its salts and by preparing appropriate derivatives were

identified by spectrophotometer, IR-spectrometer, NMR-spectrometer. The optimum yield of

obtained 2, 4-DNP [with 0.50gm and 84 ml HCl in 500 ml aqueous solution] was measured

by using spectrophotometers and conductivity meter. Various probable variations like the role

of different semiconductors, mixed semiconductors, visible and UV-light etc., was studied.

Some sets of experiments are also made in controlled conditions such as in absence of UV or

visible light, semiconductors and stirring etc.


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RESULTS AND DISCUSSION

Succinic acid was the photoproduct in the TiO2-sensitised photooxidation of dilute solution in

water of γ-hydroxybutyric acid. Following variations are studied in this part of thesis:-

(1)-The effect of substrate

The effect of amount of substrate on the oxidation of γ-hydroxybutyric acid was studied at

different concentrations varying from 0.92 × 10-2

M to 7.68 × 10-2

M (1 gm to 8 gms per litre)

at fixed amount TiO2 (1.26 × 10-2

M, i.e. 1 gm/Lt). The total volume of reaction mixture is 50

ml and the results are reported in the Table 5.25 and shown in Plot 5.25.

1. Solvent : Water

2. TiO2 : 1.26 × 10-2

M (1.00 g/L)

3. Irradiation time : 240 min

4. Visible light : 2 × 200 W Tungsten lamps

Table 5.25

S. No. Conc. Of Substrate

[γ-hydroxybutyric acid]

Percent yield of product

(Succinic acid)

1 0.90 10-2

M 28.2%

2 1.92 10-2

M 33.7%

3 2.88 10-2

M 39.6%

4 3.84 10-2

M 44.1%

5 4.80 10-2

M 52.7%

6 5.76 10-2

M 59.3%

7 6.72 10-2

M 66.2%

8 7.68 10-2

M 72.5%

Plot 5.25 The effect of substrate.


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(2) The effect of photocatalyst

Keeping all other factors identical the effect of amount of TiO2 has also been observed. The

total volume of reaction mixture is 50 mL and the results are reported in the following Table

5.26 and shown in Plot 5.26

1. Solvent : Water

2. γ-hydroxybutyric acid: 3.84 x 10-2

M (4.00 g/L)



Table 5.26

S. No. Conc. Of Substrate

(TiO2)

Percent yield of product

(Succinic acd)

1 1.251 × 10-2

M 44.1%

2 2.503 × 10-2

M 52.7%

3 3.754 × 10-2

M 59.3%

4 5.006 × 10-2

M 66.2%

5 6.257 × 10-2

M 72.5%

6 7.509 × 10-2

M 72.7%

7 8.760 × 10-2

M 72.9%

Plot 5.26 The effect of light.

(3) The effect of type of radiations

The effect of type of radiations on photocatalytic reaction was studied in visible light and

ultraviolet light keeping all other factors identical. The total volume of reaction mixture is 50


1064


mL and the results are reported in the Table 5.27 and shown in Plot 5.27.

1. Solvent : Water

2. TiO2 : 1.26 × 10-2

M (1.00 g/L)



5. UV Light : UV Chamber 30 W (Philips Tube)

Table 5.27

S.

No.

Conc. Of Substrate

[γ-hydroxybutyric

acid]

Percent yield of

product

(In visible light)

Percent yield of

product

(In UV light)

1 0.90 10-2

M 28.2% 45.3%

2 1.92 10-2

M 33.7% 51.7%

3 2.88 10-2

M 39.6% 62.3%

4 3.84 10-2

M 44.1% 68.5%

5 4.80 10-2

M 52.7% 73.6%

6 5.76 10-2

M 59.3% 78.3%

7 6.72 10-2

M 66.2% 82.0%

8 7.68 10-2

M 72.5% 86.1%

Fig. 5.27 Percent yield of product (Succinic acid).


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(4)-The effect of nature of photocatalyst

The effect of the nature of photocatalyst on photocatalytic reaction was studied by different

photocatalysts, which are Ferric oxide, Cadmium sulphide, Tungsten oxide, Titanium oxide,

Stannic oxide and Zinc sulphide. The total volume of reaction mixture is 50 ml and the

results are reported in the following Table 5.28 and shown in Plot 5.28

1. Solvent : Water

2. γ-hydroxybutyric acid : 4.80 × 10-2

M(5.00 gm)

3. Irradiation Time : 240 min.

4. Visible Light : 2 × 200 W Tungsten Lamps.

Table 5.28

S. No. Photocatalyst Band gap

(eV)

Wavelength

(nm)

Yield of

Photoproduct

1 Fe2O3 2.2 564 24.2%

2 CdS 2.4 516 28.1%

3 WO3 2.6 477 46.6%

4 TiO2 3.1 400 71.3%

5 ZnO 3.2 388 66.2%

6 SnO2 3.5 354 54.7%

7 ZnS 3.6 345 63.5%

Plot 5.28 Percent yield of product.

The effect of amount of on the oxidation of γ-hydroxybutyric acid was studied by using

variable amount of substrate, as reported in Table 5.25 and Plot 5.25. The highest efficiency

was observed at optimum concentration. It may be explained on the basis that as the


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concentration of substrate increases, more substrate molecules are available for photocatalytic

reaction and hence an enhancement on the rate was observed with increasing concentration of

substrate.

The amount of photocatalyst on oxidation of γ-hydroxybutyric acid was investigated

employing different concentrations of the TiO2 as reported in Table 5.26 and Plot 5.26. It was

observed that the yield of photo-product increasing with increasing catalyst level up to 5.006

× 10-2

M and beyond this, the yield of photo-product is constant. This observation may be

explained on the basis that on the initial stage, even a small addition of photocatalyst will

increase the yield of photoproduct as the surface area of photocatalyst increases, but after a

certain amount 5.006 × 10-2

M, addition of photocatalyst do not affect the yield of product

because of the fact that at this limiting amount, the surface at the bottom of the reaction

vessel become completely covered with photocatalyst. Now increase in the amount of

photocatalyst will only increase the thickness of the layer at the bottom. Keeping all the

factors identical the effect of the nature of photocatalyst on the photo-oxidation of γ-

hydroxybutyric acid was studied by using visible and UV light as shown in the Table 5.27and

Plot 5.27. As we know that the band gap for the formation of succinic acid is more suitable

for UV light and this property quite resembles the observed data as the table reported.

Titanium dioxide (TiO2) is the most common photocatalyst and comparably little research has

been conducted on zinc oxide, ZnO, which could be a viable alternative for some

applications. The effect of other semiconductor particle e.g. Fe2O3, CdS, WO3 (having low

band gap than TiO2 semiconductor) on the TiO2 catalyst photocatalytic reactions have also

been studied. TiO2 is the most frequently used photo catalyst because of its photo stability

and low cost, combined with its biological and chemical inertness and resistant to photo and

chemical corrosion. On the other hand, binary metal sulfide semiconductors such as CdS and

PbS are regarded as insufficiently stable for catalysis and are toxic. ZnO is also unstable in

illuminated aqueous solutions while WO3 has been investigated as a potential photo catalyst,

but it is generally less active catalytically than TiO2. However, these can be combined with

other semiconductors including TiO2 to achieve greater photo catalytic efficiency or stability.

Keeping all the factors identical the effect of the nature of photocatalyst on the photo-

oxidation of γ-hydroxybutyric acid was studied by using different photocatalysts as shown in

the Table 5.28 and Plot 5.28.


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It is now well established that the photocatalytic oxidation of several organic compounds by

optically excited semiconductor oxides is thermodynamically allowed in presence of oxygen

at room temperature. On the basis of analytical, chemical and spectral data the product was

characterized succinic acid.

Mechanism

On the basis of results and discussion the following tentative mechanistic part has discussed

for photocatalytic oxidation of γ-hydroxybutyric acid, with collaborating the results already

reported for other studied compounds.

With respect to a semiconductor oxide such as TiO2, photocatalytic reactions are initiated by

the absorption of illumination with energy equal to or greater than the band gap of the

semiconductor. When the suspension of titanium oxide irradiated with visible light electron

will be promoted from valence band to conduction band leaving a positive hole in the valence

band:

TiO2 + hv → (h – e) Excitation …(1)

(h – e) → h+ + e

– Separation …(2)

It was explained before, that the surface of TiO2 with high surface area retains subsets of

hydroxyls, where the net surface density is 4-5 hydroxyl per nm. In addition, suspension of

TiO2 in solution of γ-hydroxybutyric acid gives a surface hydroxide ion as locations for

primary photo-oxidation processes. Photo holes are trapped by surface hydroxyl groups,

whereas electrons are trapped by adsorbed oxygen:

h+ + OH

– (s) → OH

• …(3)

e– + O2 (abs) → O2

•− (abs) …(4)

The substrate γ-hydroxy butyric acid is believed to react with the formed OH• radical to form

the following γ-hydroxy butyric acid radical-

CH3(OH)CH2CH2COOH + OH• → CH2

•(OH)CH2CH2COOH + H2O ...(5)

The formed O2•−

radicals are reacted with adsorbed on the surface, is reacted with the formed

water to regenerate hydroxyl group on the surface of the catalyst:

O2•−

(abs) + H2O → OH− (s) + OH2

• …(6)

Succinic semialdehyde formed according the following steps:

CH2•(OH)CH2CH2COOH + OH2

• → CH(O)-CH2-CH2COOH + H2O2 …(7)


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CH2•(OH)CH2CH2COOH + OH

• → CH(O)-CH2-CH2COOH + H2O …(8)

2 CH2•(OH)CH2CH2COOH → CH(O)-CH2-CH2COOH + CH3(OH)CH2CH2COOH …(9)

The elementary photoproduct “Succinic semialdehyde” is detected about to one hour of

irradiation by TLC and other tests but the concentration was very poor so the irradiation time

increased up to 240 minutes. After 240 minutes of irradiation the succinic acid was found as

photoproduct in pleasant amount and that was detected well by the usual chemical tests and

derivatives of it. Hence, concluded that in these practical circumstances the succinic

semialdehyde may does not have stability and further undergoes oxidize and the final

photoproduct succinic acid is produced which was well identified by the simple chemical as

well as spectral tests.

According to references and literature available29

the further sensitized photo-oxidation of

succinic semialdehyde undergoes in the following manner. The succinic semialdehyde again

come in contact of the hole of semiconductor and its radical cation (CH(O)-CH2-

CH2COOH)•+

forms. Subsequent oxidation of this radical ion occurs with superoxide anion

radical to give succinic acid, as follows:

2(CH(O)-CH2-CH2COOH)•+

+ O2•−

(abs) → 2HOOC-CH2-CH2-COOH …(10)

The mechanism can be summarized as follows:-

Identification of Succinic acid

Adjust the pH of 5 ml of Succinic Acid solution (1 → 20) to about 7 with ammonia TS. Add

2－3 drops of ferric chloride solution (1 → 10). A brown precipitate is formed.

As discussed above γ- hydroxyl butyric acid is used illegally (under the street names juice,

liquid ecstasy, or G) as an intoxicant for increasing athletic performance and as a date rape

drug. In high doses, GHB inhibits the CNS, inducing sleep and inhibiting the respiratory


1069


drive. Hence this study arose interdisciplinary idea for biologists, chemists, pharmacists and

drug researchers to do more studies in such illegal compounds to dispose or management.

Succinic acid is a water-soluble (melting point 185－190℃), colorless crystal with an acid

taste that is used as a chemical intermediate, in medicine, the manufacture of lacquers, and to

make perfume esters. It is also used in foods as a sequestrate, buffer, and a neutralizing

agent.[30]

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