(comprising the prenyl chain attached to C5), PYR for the α-pyrone moiety, and
ARZ for arzanol.
The computational study of the ARZ molecule [5] showed that its conformational preferences are influenced by the patterns of intramolecular hydrogen bonds
(IHB), which are the dominant stabilising factor, by the mutual orientation of
the PHL and PYR moieties (which also determines part of the IHB patterns), by the
orientation of the phenol OHs (as is true for ACPLs in general [6–10]) and by the
orientation of the prenyl chain (which is generally true for prenylated ACPLs [8]).
The IHBs comprise the IHB formed by O14 and either H15 or H16 (here termed
“first IHB” [6–10]), the IHBs between the two moieties (which will be categorised
as IMHB, for ‘intermoiety H-bonds’, when it is relevant to underline this role, [5])
and the O10-H16⋯π or O12-H17⋯π interactions, when either O10-H16 or
O12-H17 and the prenyl chain have favourable orientations. The distribution of
donor and acceptor sites in the ARZ molecule enables the formation of two
simultaneous IMHBs, one on either side of the methylene bridge, and all the lowest
energy conformers are characterised by the presence of the first IHB and two
IMHBs [5]; when the first IHB engages H15, it is cooperative with the IMHB
engaging O8.
The computational study of ARZ [5] included calculations in three solvents
(chloroform, acetonitrile and water) utilising the Polarizable Continuum Model
(PCM, [11–13]). In general, “continuum solvation models are the ideal conceptual
framework to describe solvent effects within the QM approach” [13]. However,
PCM does not take into explicit account directional solute-solvent interactions such
as hydrogen bonding [14] (except implicitly for some effects [15]). On the other
hand, solute-solvent H-bonding is important for solute molecules containing
H-bond donors or acceptors and solvent molecules capable of forming H-bonds.
The most important of these solvents is water, which constitutes the highest proportion of the mass of living organisms. The consideration of adducts with explicit
water molecules is the most informative option on solute-solvent H-bonding utilising QM approaches. It can provide information about preferential arrangements of
water molecules in the vicinity of the various donor or acceptor sites. It can also
contribute information on the outcome of the competition between intramolecular
H-bonding and intermolecular solute-water H-bonding through energetics comparisons (by comparing an adduct maintaining a certain IHB and an adduct in
which its donor or acceptor is engaged in a solute-solvent H-bond), and also
through the optimisation itself, which may ‘open’ (break) specific IHBs, as verified,
e.g., in the study of adducts of caespitate [16] or other ACPLs [17] with explicit
water molecules.
This work considers adducts of various conformers of ARZ with explicit water
molecules, trying to identify patterns for the energy of the solute-solvent interaction
at different binding sites and for preferred arrangements of water molecules around
different sites of the ARZ molecule. The study appears to be particularly interesting
because of the high number of H-bond donors and acceptors in the ARZ molecule
and because of the presence of IHBs (including cooperative ones), which influences
the way in which water molecules approach the corresponding regions. The work
Adducts of Arzanol with Explicit Water Molecules …
283
ARZ for arzanol.
The computational study of the ARZ molecule [5] showed that its conformational preferences are influenced by the patterns of intramolecular hydrogen bonds
(IHB), which are the dominant stabilising factor, by the mutual orientation of
the PHL and PYR moieties (which also determines part of the IHB patterns), by the
orientation of the phenol OHs (as is true for ACPLs in general [6–10]) and by the
orientation of the prenyl chain (which is generally true for prenylated ACPLs [8]).
The IHBs comprise the IHB formed by O14 and either H15 or H16 (here termed
“first IHB” [6–10]), the IHBs between the two moieties (which will be categorised
as IMHB, for ‘intermoiety H-bonds’, when it is relevant to underline this role, [5])
and the O10-H16⋯π or O12-H17⋯π interactions, when either O10-H16 or
O12-H17 and the prenyl chain have favourable orientations. The distribution of
donor and acceptor sites in the ARZ molecule enables the formation of two
simultaneous IMHBs, one on either side of the methylene bridge, and all the lowest
energy conformers are characterised by the presence of the first IHB and two
IMHBs [5]; when the first IHB engages H15, it is cooperative with the IMHB
engaging O8.
The computational study of ARZ [5] included calculations in three solvents
(chloroform, acetonitrile and water) utilising the Polarizable Continuum Model
(PCM, [11–13]). In general, “continuum solvation models are the ideal conceptual
framework to describe solvent effects within the QM approach” [13]. However,
PCM does not take into explicit account directional solute-solvent interactions such
as hydrogen bonding [14] (except implicitly for some effects [15]). On the other
hand, solute-solvent H-bonding is important for solute molecules containing
H-bond donors or acceptors and solvent molecules capable of forming H-bonds.
The most important of these solvents is water, which constitutes the highest proportion of the mass of living organisms. The consideration of adducts with explicit
water molecules is the most informative option on solute-solvent H-bonding utilising QM approaches. It can provide information about preferential arrangements of
water molecules in the vicinity of the various donor or acceptor sites. It can also
contribute information on the outcome of the competition between intramolecular
H-bonding and intermolecular solute-water H-bonding through energetics comparisons (by comparing an adduct maintaining a certain IHB and an adduct in
which its donor or acceptor is engaged in a solute-solvent H-bond), and also
through the optimisation itself, which may ‘open’ (break) specific IHBs, as verified,
e.g., in the study of adducts of caespitate [16] or other ACPLs [17] with explicit
water molecules.
This work considers adducts of various conformers of ARZ with explicit water
molecules, trying to identify patterns for the energy of the solute-solvent interaction
at different binding sites and for preferred arrangements of water molecules around
different sites of the ARZ molecule. The study appears to be particularly interesting
because of the high number of H-bond donors and acceptors in the ARZ molecule
and because of the presence of IHBs (including cooperative ones), which influences
the way in which water molecules approach the corresponding regions. The work
Adducts of Arzanol with Explicit Water Molecules …
283