1 Introduction
Muchimangin B (C 31 H 28 O 11 , Fig. 1) is a xanthone derivative isolated from the root
of Securidaca longepedunculata, a plant utilised in traditional medicine in the DR
Congo [1]. It exhibits activity against pancreatic cancer [1], a type of cancer largely
resistant to most anticancer drugs currently in clinical use.
Biologically active compounds of natural origin are important sources of new
active molecular structures, because they are already known to possess a certain
type of desired activity and already known to be compatible with a living organism
and to be able to reach their targets within the organism. Detailed information about
the molecular properties of a biologically active compound is important for the
design of compounds with more potent activities [2]. It is important to know as
many details of the molecular properties as possible, as the biological activity may
be related to the finest details of these properties [3]. This motivates detailed
computational studies of biologically active molecules.
The current study investigates the conformational preferences of muchimangin B
(concisely denoted by the acronym MUCH-B in the rest of the text) in vacuo and in
three solvents with different polarities and different hydrogen-bonding abilities—
chloroform, acetonitrile and water. Considering solvents with different polarities is
important to take into account the possible environments in which a molecule may
be present within a living organism. The octanol/water partition coefficient of
MUCH-B (4.23138, estimated with [4]) suggests that it is mostly present in nonpolar media. However, the dominant presence of water in living organisms recommends its inclusion in the range of solvents considered for a biologically active
molecule. Chloroform is a good model for non-polar media, and acetonitrile has
intermediate polarity and is also a suitable model for the medium in cellular
membranes. Considering solvents with different H-bonding abilities is important for
molecules containing H-bond donor or acceptor sites.
The results show the dominant role of intramolecular hydrogen bonds (IHB) in
determining the conformational preferences and relative energies of MUCH-B,
followed by the orientation of the two rings with respect to the xanthone moiety.
The results in solution show the changes of the molecular properties with increasing
solvent polarity. The solvent-stabilising effect is greater for water.
2 Computational Details
Calculations in vacuo with full geometry optimization (fully relaxed geometry) were
performed at two levels of theory: Hartree-Fock (HF/6-31G(d,p)) and density
functional theory with the B3LYP functional (DFT/B3LYP/6-31+G(d,p)). In addition, Møller-Plesset perturbation theory (MP2/6-31G(d,p)) calculations were performed as single point (SP) calculations on the HF-optimized results.
HF can be expected to give reasonable information for conformational aspects,
including the identification of trends. It can also be considered interesting for
92
L. Mammino et al.
Muchimangin B (C 31 H 28 O 11 , Fig. 1) is a xanthone derivative isolated from the root
of Securidaca longepedunculata, a plant utilised in traditional medicine in the DR
Congo [1]. It exhibits activity against pancreatic cancer [1], a type of cancer largely
resistant to most anticancer drugs currently in clinical use.
Biologically active compounds of natural origin are important sources of new
active molecular structures, because they are already known to possess a certain
type of desired activity and already known to be compatible with a living organism
and to be able to reach their targets within the organism. Detailed information about
the molecular properties of a biologically active compound is important for the
design of compounds with more potent activities [2]. It is important to know as
many details of the molecular properties as possible, as the biological activity may
be related to the finest details of these properties [3]. This motivates detailed
computational studies of biologically active molecules.
The current study investigates the conformational preferences of muchimangin B
(concisely denoted by the acronym MUCH-B in the rest of the text) in vacuo and in
three solvents with different polarities and different hydrogen-bonding abilities—
chloroform, acetonitrile and water. Considering solvents with different polarities is
important to take into account the possible environments in which a molecule may
be present within a living organism. The octanol/water partition coefficient of
MUCH-B (4.23138, estimated with [4]) suggests that it is mostly present in nonpolar media. However, the dominant presence of water in living organisms recommends its inclusion in the range of solvents considered for a biologically active
molecule. Chloroform is a good model for non-polar media, and acetonitrile has
intermediate polarity and is also a suitable model for the medium in cellular
membranes. Considering solvents with different H-bonding abilities is important for
molecules containing H-bond donor or acceptor sites.
The results show the dominant role of intramolecular hydrogen bonds (IHB) in
determining the conformational preferences and relative energies of MUCH-B,
followed by the orientation of the two rings with respect to the xanthone moiety.
The results in solution show the changes of the molecular properties with increasing
solvent polarity. The solvent-stabilising effect is greater for water.
2 Computational Details
Calculations in vacuo with full geometry optimization (fully relaxed geometry) were
performed at two levels of theory: Hartree-Fock (HF/6-31G(d,p)) and density
functional theory with the B3LYP functional (DFT/B3LYP/6-31+G(d,p)). In addition, Møller-Plesset perturbation theory (MP2/6-31G(d,p)) calculations were performed as single point (SP) calculations on the HF-optimized results.
HF can be expected to give reasonable information for conformational aspects,
including the identification of trends. It can also be considered interesting for
92
L. Mammino et al.