Complexes of Furonewguinone B with a Cu 2+ Ion. A DFT Study
161
with antioxidant properties [6–8]. Antioxidant compounds help protect the organism
against reactive oxygen species, whose excessive presence appears to increase the risk
of degenerative diseases such as ischemia, Alzheimer disease, Parkinson disease and
schizophrenia [9–11]. Biologically active compounds of natural origin are viewed as
particularly promising for drug development because of their proven compatibility
with a living organism and ability to reach their biological target. Understanding the
molecular origin of the activity of a compound is relevant for the design of compounds with more potent activity [12]; the initial step is the identification of the
features influencing the properties of a molecule.
Several phenolic compounds (commonly present in plants as secondary metabolites [13]) exhibit antioxidant activity, which can be ascribed to the presence of phenol
OHs. Possible mechanisms for this activity have been objects of intensive studies
[13–24]. It has been established that the activity is enhanced by the presence of ortho
OHs (whose intramolecular hydrogen bond contributes to stabilize the molecular
radical formed at some stage of the antioxidant action) and by the presence of a C=C
double bond in a suitable position in a substituent [14, 16].
Because of containing three phenol OHs, ACPLs could be expected to have good
antioxidant properties, and they are actually viewed as potentially interesting lead
compounds for the development of drugs against degenerative diseases [25]. Their
phenol OHs cannot form intramolecular hydrogen bonds (IHB) with each other,
because of being mutually meta. On the other hand, ACPLs are characterised by a
comparatively strong IHB between the sp
2 O in the CRO group and an ortho OH
([26–28]), which may have a role in their antioxidant action. ACPLs of natural origin
reported to have interesting antioxidant activity [1–5, 9, 29–31] contain substituents
with C=C double bonds, such as a prenyl or a geranyl chain, or additional OH groups,
or both.
The FNGB molecule contains a furanoid ring fused to the phloroglucinol ring
between C3 and C4, and a prenyl chain at C5. It contains four OH groups and two
sp
2 O atoms. It differs from hyperguinone B (HPGB [8]) by the nature of the ring
fused along the C3–C4 bond and by the presence of three additional OHs, at C2,
C4 and C27. The conformers of FNGB are characterised by different IHB patterns.
The H15···O14 IHB (here termed “first IHB” for analogy with previous studies on
ACPLs) is the strongest, as the acceptor is an sp
2 O. Additional O–H···O IHBs are
possible and have stabilising effects [32]; O–H···π IHBs are also possible and also
have stabilising effects [33].
After a preliminary conformational study of the uncomplexed FNGB molecule,
the current work focuses on the ability of FNGB to coordinate a Cu
2+ ion and reduce
it to Cu
+ . This is a way of modelling the molecule’s antioxidant ability [12, 34]. Metal
chelation is also viewed as a possible pathway in the mechanisms of the antioxidant
activity of polyhydroxybenzenes [13], which contributes to the significance of this
type of modelling.
The FNGB molecule contains eight sites apt to bind Cu
2+ : the seven O atoms
(four in the four OH groups, two sp
2 O and the O heteroatom in the furanoid ring)
and the C21=C22 π bond in the prenyl chain (π1). Complexes were calculated for
all the significantly different conformers of FNGB, considering each binding site
161
with antioxidant properties [6–8]. Antioxidant compounds help protect the organism
against reactive oxygen species, whose excessive presence appears to increase the risk
of degenerative diseases such as ischemia, Alzheimer disease, Parkinson disease and
schizophrenia [9–11]. Biologically active compounds of natural origin are viewed as
particularly promising for drug development because of their proven compatibility
with a living organism and ability to reach their biological target. Understanding the
molecular origin of the activity of a compound is relevant for the design of compounds with more potent activity [12]; the initial step is the identification of the
features influencing the properties of a molecule.
Several phenolic compounds (commonly present in plants as secondary metabolites [13]) exhibit antioxidant activity, which can be ascribed to the presence of phenol
OHs. Possible mechanisms for this activity have been objects of intensive studies
[13–24]. It has been established that the activity is enhanced by the presence of ortho
OHs (whose intramolecular hydrogen bond contributes to stabilize the molecular
radical formed at some stage of the antioxidant action) and by the presence of a C=C
double bond in a suitable position in a substituent [14, 16].
Because of containing three phenol OHs, ACPLs could be expected to have good
antioxidant properties, and they are actually viewed as potentially interesting lead
compounds for the development of drugs against degenerative diseases [25]. Their
phenol OHs cannot form intramolecular hydrogen bonds (IHB) with each other,
because of being mutually meta. On the other hand, ACPLs are characterised by a
comparatively strong IHB between the sp
2 O in the CRO group and an ortho OH
([26–28]), which may have a role in their antioxidant action. ACPLs of natural origin
reported to have interesting antioxidant activity [1–5, 9, 29–31] contain substituents
with C=C double bonds, such as a prenyl or a geranyl chain, or additional OH groups,
or both.
The FNGB molecule contains a furanoid ring fused to the phloroglucinol ring
between C3 and C4, and a prenyl chain at C5. It contains four OH groups and two
sp
2 O atoms. It differs from hyperguinone B (HPGB [8]) by the nature of the ring
fused along the C3–C4 bond and by the presence of three additional OHs, at C2,
C4 and C27. The conformers of FNGB are characterised by different IHB patterns.
The H15···O14 IHB (here termed “first IHB” for analogy with previous studies on
ACPLs) is the strongest, as the acceptor is an sp
2 O. Additional O–H···O IHBs are
possible and have stabilising effects [32]; O–H···π IHBs are also possible and also
have stabilising effects [33].
After a preliminary conformational study of the uncomplexed FNGB molecule,
the current work focuses on the ability of FNGB to coordinate a Cu
2+ ion and reduce
it to Cu
+ . This is a way of modelling the molecule’s antioxidant ability [12, 34]. Metal
chelation is also viewed as a possible pathway in the mechanisms of the antioxidant
activity of polyhydroxybenzenes [13], which contributes to the significance of this
type of modelling.
The FNGB molecule contains eight sites apt to bind Cu
2+ : the seven O atoms
(four in the four OH groups, two sp
2 O and the O heteroatom in the furanoid ring)
and the C21=C22 π bond in the prenyl chain (π1). Complexes were calculated for
all the significantly different conformers of FNGB, considering each binding site