Computational study of the patterns of weaker intramolecular hydrogen bonds stabilizing acylphloroglucinols

Abstract

Acylphloroglucinols (ACPLs) are polyphenolic compounds derivative from phloroglucinol, characterized by the presence of at least one COR group and exhibiting a variety of biological activities, which makes them interesting for drug development possibilities. This study investigates patterns in the ways in which weaker intramolecular hydrogen bonds contribute to their conformational stabilization, considering the CH···O H‐bonds, present in all ACPLs, and the OH···π H‐bonds, present in ACPLs in which one or more substituents contain a π bond or system sufficiently close to a phenol OH for the H‐bond to be possible. The results in vacuo and in three different solvents (chloroform, acetonitrile, and water) show that, whereas CH···O plays a significant roles in all these media, the role of OH···π decreases with increasing solvent polarity. Calculations in vacuo are performed at various levels to enable performance comparisons; calculations in solution use the polarizable continuum model. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011

Antioxidant and antimalarial properties of butein and homobutein based on their ability to chelate iron (II and III) cations: a DFT study in vacuo and in solution

“…In a similar manner, the para substituted OH group (O4H4) in ring B can interact with neighbouring O3 to form an IHB, here called the second H-bond and denoted as HB2. IHBs are known to stabilise conformations [47][48][49][50][51][52][53][54][55] as well as to influence the biological activities of compounds, such as antioxidant activity [24,25,32,34].…”

Intramolecular Hydrogen Bonding and Conformational Preferences of Arzanol—An Antioxidant Acylphloroglucinol

“…Calculations were performed with the same levels of theory as in previous studies of ACPLs [ 7 , 8 , 9 , 10 , 11 ], to enable informative comparisons: Hartree Fock (HF) with the 6-31G(d,p) basis set and Density Functional Theory (DFT) with the B3LYP functional and the 6-31+G(d,p) basis set, both with fully relaxed geometry, and MP2 single-point (SP) calculations on the HF-optimised conformers. The general studies of ACPLs [ 7 , 8 , 9 , 10 , 11 ] had shown that HF gives reasonable results for this class of compounds and enables realistic trend-identifications with the reasonably cheap 6-31G(d,p) basis set.…”

“…ACPLs [ 6 ] are derivatives of phloroglucinol (1,3,5-trihydroxybenzene) characterised by the presence of a COR group (acyl group), whose sp 2 O can form an intramolecular hydrogen bond (IHB) with one of the two ortho OHs; following a practice introduced in previous works on ACPLs [ 7 , 8 , 9 , 10 , 11 ], this IHB (which is present in nearly all ACPLs) is here termed ‘first IHB’. In arzanol, R is a methyl group; an α-pyrone ring is attached to one position meta to the COR group (C3) and a prenyl chain is attached to the other meta position (C5).…”

“…The computational study of antioxidant ACPLs responds to the known tight relationships between the molecular properties of polyphenolic compounds and their biological activities [ 12 , 13 , 14 ]. The study of the ARZ molecule is also interesting in view of new information on ACPLs, as the fact that the PHL moiety is bonded to a ring of a different nature (PYR) makes ARZ different from the ACPLs considered so far [ 7 , 8 , 9 , 10 , 11 ], including the dimeric ACPLs in which both units are acylphloroglucinol moieties [ 15 ].…”

“…Conformers were calculated in the gas phase and in solution, considering the same three solvents as in the previous studies of ACPLs (chloroform, acetonitrile and water, [ 7 , 8 , 9 , 10 , 11 ]) to enable informative comparisons. These solvents cover the ranges of polarities and H-bonding abilities of the media in which a biologically active molecule may preferably be present within a living organism.…”