Phenolphthalein

phenolphthalein, with the formula C₂₀H₁₄O₄, is a pH indicator that in In acid solutions it remains colorless, but in basic solutions it takes on a pink color with a turning point between pH=8.2 (colorless) and pH=10 (magenta or pink). However, at extreme pH (very acidic or basic) it presents other color changes: phenolphthalein in strongly basic solutions turns colorless, while in strongly acidic solutions it turns orange.

It is an organic chemical compound that is obtained by the reaction of phenol (C₆H₅OH) and phthalic anhydride (C₈ H₄O₃) in the presence of sulfuric acid.

Pharmacology and others

In pharmacology and therapy it is used as a cathartic laxative. In Mexico and other countries, despite the fact that its use as a medicine has been limited given the assumption that it has carcinogenic effects, it was incorporated into the homeopathic pharmacopoeia and continues to be sold in pharmacies as a homeopathic specialty. In Chile, the ethical presentation of the drug continues to be sold.

In clinical tests, phenolphthalein is used as a diagnostic agent to investigate kidney function and in the determination of residual urine in the bladder. Here an injectable form of the drug is used.

In microbiology, this chemical compound is also used in the form of phenolphthalein diphosphate for the identification of specific bacteria (positive for acid phosphatase) in some selective culture media.

Background

The cathartic action of phenolphthalein was discovered accidentally. Towards the end of the 18th century the government of Hungary, to help its people buy cheap wine, decreed that adulterated wine was marked with phenolphthalein, since in the presence of alkali it turned bright red and was supposed to be innocuous. It was soon seen that those who drank the drink suffered from diarrhea, thus discovering a new purgative.

Action

The action of the drug is similar to that of the anthracene group and exerts a stimulating effect on intestinal peristalsis by direct action on the nerve endings of the colon. Since it is a compound that is insoluble in water but forms soluble salts with alkalis, its action depends to some degree on the alkalinity of the gastrointestinal tract.

Pharmacokinetics

A therapeutic dose passes through the stomach unchanged and is dissolved in the intestine by the combined action of bile salts and alkaline intestinal contents. About 15% is absorbed into the circulation; the remainder appears unchanged in the feces. A portion of what is absorbed appears in the urine, which if it becomes alkaline will have a red coloration, and another portion is excreted back into the intestinal tract with the bile, which again increases intestinal activity and its effects continue to be felt. 3 or 4 days after its initial administration. The action begins 4 or 8 hours after oral administration and is effective as a purgative, showing little colic action. In the late 1960s and early 1970s, approximately 28 pharmaceutical preparations containing phenolphthalein as the main ingredient were registered.

Undesirable effects

At high doses and in susceptible people an excessive purgative effect, colic, palpitations, altered breathing and collapse may occur. A fatal case has been registered due to the use of phenolphthalein

Other manifestations are dermatitis in the form of erythema multiforme or pink macular plaques that can become purple. Burning and stinging sensation may be felt.

Derivatives of phenolphthalein have been synthesized but cathartic activity was found to be much lower in those derivatives in which the benzene portion of the carbon skeleton was lengthened by substitution or when the phthalide was replaced by phthalamide or anthrone.

Description and uses

It usually occurs as a white powder that melts at 260 °C. It is frequently used as a non-extreme pH indicator, since in acid solutions (not extremely very acid) it remains colorless, but in the presence of basic solutions (not extremely very basic) it turns pink. In chemistry it is used in laboratory analysis, research and fine chemistry. In chemical analysis it is used as an indicator of acid-base titrations, its turning point being around the pH value 9, making the chromatic transition from colorless to pink. The reagent is prepared at 1% w/v in 90° alcohol and has an indefinite shelf life.

Other uses: Phenolphthalein is used as a reagent in the Kastle-Meyer test, to detect trace amounts of blood.

Chemical properties

Colour changes occur in certain pH ranges, and can be described by the following chemical equations:

From neutral medium to basic medium:
H₂Phenolphthalein + 2 OH^- ↔ Phenolphthalein^2- + 2 H₂O
Colorless → Pink

From medium basic to medium very basic:
Phenolphthalein^2- + OH^- ↔ Phenolphthalein(OH)^3-
Pink → Colorless

From a basic medium to a neutral or acid medium:
Phenolphthalein^2- + 2 H⁺ ↔ H₂Phenolphthalein
Pink → Colorless

From a neutral or acid medium to a very acid medium:
H₂Phenolphthalein + H⁺ ↔ H₃Phenolphthalein⁺
Colorless → Orange

Thus, in strongly basic solutions, phenolphthalein becomes colorless. In strongly acidic solutions it is orange. Therefore it has different intervals of action:

Species	H3Fenolftaleine+	H2Fenolftaleine	Fenolftaleine2−	Fenolftaleine(OH)3−
Structure
Model
pH	¢Ü	0−8.2	8.2−9.8	9,8-12,0
Conditions	strongly acid	acid or neutral	basic	strongly basic
Color	orange	colorless	Pink	colorless
Image

Reaction mechanisms: H3In+ → H2In → In2− → In(OH)3−

Phenolphthalein is normally dissolved in alcohol for use in experiments. Phenolphthalein is a weak acid that loses H⁺ cations in solution. The phenolphthalein molecule is colorless, whereas the anion derived from phenolphthalein is pink. When a base is added, phenolphthalein (being initially colorless) loses H⁺, forming the anion and causing it to take on a pink color. The color change cannot be explained on the basis of deprotonation alone, a structural change occurs with the appearance of a ketoenolic tautomerism.

Precautions

In people with jaundice, phenolphthalein has no effect. Children under two years of age should not take it. Idiosyncrasies to the drug may occur.

Pharmaceutical presentations

• It can be found in 60 mg tablets. If presented yellowly, it is a less purified form of the drug.
• Solution bottle with 50 g.
• Dissolution indicates 1 percent phenolfthalein.