Fluorination as a route towards unlocking the hydrogen bond donor ability of phenolic compounds in self-assembled monolayers

Pinfold, Harry; Pattison, Graham; Costantini, Giovanni

doi:10.1039/d0ce00213e

Cited by 3 publications

(2 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Medicinal chemists who are making oxygen to fluorine bioisosteric replacements need to understand the effects this replacement will have on the physicochemical properties of a molecule, particularly lipophilicity because of the key role it plays in biodistribution, metabolism, and binding. As part of our interest in the chemistry of fluorinated aromatic compounds, − in this paper, we will describe how structural features in a drug-like molecule may affect the change in lipophilicity on transformation of an aromatic hydroxy or methoxy group to a fluorine atom.…”

Section: Introductionmentioning

confidence: 99%

Effects of Replacing Oxygenated Functionality with Fluorine on Lipophilicity

Glyn

Pattison

2021

J. Med. Chem.

Self Cite

View full text Add to dashboard Cite

The replacement of oxygenated functionality (hydroxy and alkoxy) with a fluorine atom is a commonly used bioisosteric replacement in medicinal chemistry. In this paper, we use molecular matched-pair analysis to better understand the effects of this replacement on lipophilicity. It seems that the reduced log P of the oxygenated compound is normally dominant in determining the size of this difference. We observe that the presence of additional electron-donating groups on an aromatic ring generally increases the difference in lipophilicity between an oxygenated compound and its fluorinated analogue, while electron-withdrawing groups lead to smaller differences. Ortho-substituted compounds generally display a reduced difference in log P compared to para- and meta-substituted compounds, particularly if an ortho-substituent can form an intramolecular hydrogen bond. Hydrogen-bond acceptors remote to an aromatic ring containing fluorine/oxygen can also reduce the difference in log P between oxygen- and fluorine-substituted compounds.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of Replacing Oxygenated Functionality with Fluorine on Lipophilicity

Glyn

Pattison

2021

J. Med. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the magnitude of this increase is poorly understood, as is how other functional groups that are present in a molecule may affect this magnitude. As part of an interest in the chemistry of fluorinated aromatic compounds, [25][26][27][28][29][30][31] in this paper we will describe how structural features in a drug-like molecule may affect the change in lipophilicity on transformation of an aromatic hydroxy or methoxy group to a fluorine atom.…”

Section: Introductionmentioning

confidence: 99%

The Effects on Lipophilicity of Replacing Oxygenated Functionality with Their Fluorinated Bioisosteres

Glyn¹,

Pattison²

2021

Preprint

Self Cite

View full text Add to dashboard Cite

The replacement of oxygenated functionality (hydroxy, alkoxy) with a fluorine atom is a very commonly used bioisosteric replacement in medicinal chemistry. In this paper we use a Molecular Matched Pair Analysis approach to better understand the effects of this bioisosteric replacement on the physicochemical properties of compounds, particularly in terms of lipophilicity. We observe that the presence of electron-donating groups on an aromatic ring generally increase the difference in lipophilicity between an oxygenated compound and its fluorinated analogue.

show abstract

The Effects on Lipophilicity of Replacing Oxygenated Functionality with Their Fluorinated Bioisosteres

Rj¹,

Pattison

2021

Preprint

View full text Add to dashboard Cite

show abstract

Fluorination as a route towards unlocking the hydrogen bond donor ability of phenolic compounds in self-assembled monolayers

Abstract: Fluorination turns a prototypical diphenol into an effective hydrogen-bond-donating building block for the formation of 2D phenol–pyridine cocrystals.

Cited by 3 publications

References 34 publications

Effects of Replacing Oxygenated Functionality with Fluorine on Lipophilicity

Effects of Replacing Oxygenated Functionality with Fluorine on Lipophilicity

The Effects on Lipophilicity of Replacing Oxygenated Functionality with Their Fluorinated Bioisosteres

The Effects on Lipophilicity of Replacing Oxygenated Functionality with Their Fluorinated Bioisosteres

Contact Info

Product

Resources

About