4-Aminobenzoic acid

4-Aminobenzoic acid (also known as para-aminobenzoic acid or PABA because the two functional groups are attached to the benzene ring across from one another in the para position) is an organic compound with the formula H₂NC₆H₄CO₂H. PABA is a white crystalline solid, although commercial samples can appear gray. It is slightly soluble in water. It consists of a benzene ring substituted with amino and carboxyl groups. The compound occurs extensively in the natural world.

Production and occurrence

In industry, PABA is prepared mainly by two routes:

• Reduction of 4-nitrobenzoic acid
• Hoffman degradation of the monoamide derived from terephthalic acid.

Food sources of PABA include liver, brewer's yeast (and unfiltered beer), kidney, molasses, mushrooms, and whole grains. Other food sources of PABA include spinach, liver, and oat seeds.

Biology

Biochemistry

File:THFsynthesis pathway.svg

Tetrahydrofolate synthesis pathway

PABA is an intermediate in the synthesis of folate by bacteria, plants, and fungi. Many bacteria, including those found in the human intestinal tract such as E. coli, generate PABA from chorismate by the combined action of the enzymes 4-amino-4-deoxychorismate synthase and 4-amino-4-deoxychorismate lyase. Plants produce PABA in their chloroplasts, and store it as a glucose ester (pABA-Glc) in their tissues. Humans lack the enzymes to convert PABA to folate and so require folate from dietary sources, such as green leafy vegetables. In humans, PABA is considered nonessential and, although it has been referred to historically as "vitamin B_x", is no longer recognized as a vitamin because the typical human gut microbiome generates PABA on its own.

Sulfonamide drugs are structurally similar to PABA, and their antibacterial activity is due to their ability to interfere with the conversion of PABA to folate by the enzyme dihydropteroate synthetase. Thus, bacterial growth is limited through folate deficiency.

Medical use

The potassium salt is used as a drug against fibrotic skin disorders, such as Peyronie's disease, under the brand name Potaba. PABA is also occasionally used in pill form by sufferers of irritable bowel syndrome to treat its associated gastrointestinal symptoms, and in nutritional epidemiological studies to assess the completeness of 24-hour urine collection for the determination of urinary sodium, potassium, or nitrogen levels. PABA derivatives have also been proposed to function as acetylcholinesterase inhibitors in diseases that cause deficient cholinergic systems, such as Alzheimer's Disease.

Nutritional supplement

Despite the lack of any recognized syndromes of PABA deficiency in humans, except for those who lack the colonic bacteria that generate PABA, many claims of benefit are made by commercial suppliers of PABA as a nutritional supplement. The benefit is claimed for fatigue, irritability, depression, weeping eczema (moist eczema), scleroderma (premature hardening of the skin), patchy pigment loss in the skin (vitiligo), and premature grey hair.

Commercial and industrial use

PABA finds use in the biomedical sector. Its derivatives are found as a structural component in 1.5% of a database of 12111 commercial drugs. Other uses include its conversion to specialty azo dyes and crosslinking agents. PABA is also used as a biodegradable pesticide, though its use is now limited due to evolution of new variants of bio-pesticides. Specifically, studies have shown that PABA photodegrades through an O2-mediated pathway in which PABA is oxidized by O2 via hydrogen abstraction and decarboxylation.

In the past, PABA was widely used in sunscreens as a UV filter. It is a UVB absorber, meaning it can absorb wavelengths between 290 and 320 nm. while still allowing UVA wavelengths between 320-400 nm to pass through, producing a tan. The chemical structure of PABA, with the amino and carboxyl groups being para to each other, allows for easy electron delocalization, which reduces the gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). This makes it easier for the electrons in PABA to transition to a higher energy state upon absorbing light. Patented in 1943, PABA was one of the first active ingredients to be used in sunscreen. The first in vivo studies on mice showed that PABA reduced UV damage. In addition, it was shown to protect against skin tumors in rodents, as shown by a 1975 study ran by Dr. Diane Sekura Snyder and Dr. Marian May. However, animal and in vitro studies in the early 1980s suggested PABA might increase the risk of cellular UV damage. On the basis of these studies, as well as problems with allergies and clothing discoloration, PABA fell out of favor as a sunscreen. In 2008 it was banned as a sunscreen ingredient in the European Union and in 2019 the FDA proposed its limited use. However, water-insoluble PABA derivatives such as padimate O are currently used in some cosmetic products including mascara, concealer, and matte lipsticks.

As of 2008, the advancement of new sunscreen is focused on developing a broad spectrum of active ingredients that provide consistent protection across all wavelengths, including UVA. Researchers are considering the PABA–TiO₂ Hybrid Nanostructures that result from the method of aqueous in situ synthesis with PABA and TiO₂.

Safety considerations

PABA is largely nontoxic; the median lethal dose of PABA in dogs (oral) is 2 g/kg. Allergic reactions, specifically Allergic Contact Dermatitis and Photocontact Dermatitis, to PABA can occur. It is formed in the metabolism of certain ester local anesthetics, and many allergic reactions to local anesthetics are the result of reactions to PABA.