Abstract/Summary

OBJECTIVES: This work aims to design, synthesise and characterise replacement Natural Moisturising Factor (NMF) composed of modified hygroscopic linear amino acids to pre-empt or repair skin barrier dysfunction. METHODS: Following synthesis and characterisation, thermo-gravimetric analysis and quantum mechanics molecular modelling quantified and depicted water-binding to the new compounds. Deliquescence relative humidity demonstrated the water-scavenging ability of the compounds, while snake skin moisturising studies showed they increased water uptake into snake skin. RESULTS: From thermal analysis, N-hydroxyglycine showed greatest water-holding capacity followed by N-hydroxyserine, L-homoserine and α-hydroxyglycine; coupled with quantum mechanics molecular modelling, between 8 and 12 molecules of water could associate with each molecule of either N-hydroxyglycine, N-hydroxyserine or L-homoserine. All of our modified amino acids were efficacious and induced similar or greater water uptake compared to the established moisturising compounds hyaluronic acid, glycerine and urea in snake skin. Incorporated at 10% in Oilatum, N-hydroxyserine induced >200% greater moisture uptake into dry snake skin compared to treatment with water alone, with efficacy related to the molecules structure and ability to bind to 12 water molecules. Oilatum cream spiked with all our unnatural amino acid hydrotropes increased water uptake into snake skin compared to Oilatum alone. The compound series was designed to elucidate some structure – efficacy relationships. Amino acid chirality did not affect the water holding capacity but did affect uptake into skin. Compounds with high melting points and bond energies tended to decrease water holding capacity. With isosteric replacement, the more electronegative atoms gave greater water holding capacities.