Rovinj 2003

1
THE INFLUENCE OF AMINO ACID SIDE CHAINS ON
WATER BINDING TO THE COPPER(II) IN COPPER(II)
COMPLEXES AN EPR AND A MOLECULAR MECHANICS
STUDY Krunoslav Mirosavljevic1, Jasmina
Sabolovic2, Vesna Nöthig-Laslo1 1Ruder Boškovic
Institute 2Institute for Medical Research and
Occupational Health Zagreb, Croatia
INTRODUCTION Copper(II) complexes with amino
acids and peptides are potentially good enzyme
mimetics. Interactions of amino acid side chains
in those complexes may have important role in
their temperature dependent behaviour. The EPR
studies of the Brownian motion of
bis(N,N-dimethyl-L-?-valinato)copper(II)
(Cu(Me2Val)2) and bis(N,N-dimethyl-L-?-leucinato)c
opper(II) (Cu(Me2Leu)2) dissolved in different
solvents (deuterated methanol, 280-320 K, and
deuterated chloroform, 265-305 K) were combined
with molecular mechanics calculations. The
conformational analysis of these compounds was
performed in order to find the most stable
conformations. The aim of this work was to find
whether different EPR behaviour of these two
copper(II) complexes could be connected with the
conformational (sterical) reasons.
Bis(N,N-dimethyl-L-?-alaninato)copper(II)
(Cu(Me2Ala)2) was used as reference complex.
There are no interactions of alanine side chains
because CH3 is small group and the apical water
molecule must be present for the stability of the
complex. The effective volume of the complex is
constant in temperature interval examined.
THEORY AND RESULTS
Because of the incomplete averaging of
interaction between magnetic moments of an
electron and a nuclear spin, line widths in EPR
spectra, ?B, depend on nuclear magnetic moment,
mI . It provides that line widths obtained in EPR
spectra can be expressed
g? g?? g? A?/mT A??/mT A?/mT
Cu(Me2Ala)2
CD3OD 2.117 ?0.001 2.241 ?0.001 2.055 ?0.001 7.39 ?0.01 18.27 ?0.01 1.95 ?0.01
Cu(Me2Leu)2
CDCl3 2.116 ?0.001 2.243 ?0.001 2.053 ?0.001 9.40 ?0.01 17.90 ?0.01 5.15 ?0.01
CD3OD 2.133 ?0.001 2.244 ?0.001 2.078 ?0.001 7.80 ?0.01 17.80 ?0.01 2.80 ?0.01
Cu(Me2Val)2
CDCl3 2.117 ?0.001 2.251 ?0.001 2.050 ?0.001 9.45 ?0.01 17.90 ?0.01 5.23 ?0.01
CD3OD 280-295 K 2.129 ?0.001 2.244 ?0.001 2.072 ?0.001 8.20 ?0.01 18.50 ?0.01 3.05 ?0.01
CD3OD 295 -317 K 2.126 ?0.001 2.244 ?0.001 2.067 ?0.001 8.40 ?0.01 18.50 ?0.01 3.35 ?0.01
?B(mI) a b mI c mI2
Parameter b is varied by temperature and it is
connected with ??
Reorientation correlation time,??, depends on
viscosity to temperature ratio,?/T, according to
Stokes-Einstein relation
Table 1. EPR parameters used for calculations of
??.
DISCUSION AND CONCLUSION
The EPR spectra of Cu(Me2Leu)2 both in CDCl3 and
CD3OD suggest aqua-complex (D2O in coordination
sphere of copper) in whole temperature interval
examined. In each solvent the spectra
were simulated with the same parameters (A0 and
g0). The conformational analysis backs EPR
results the energy difference between the
most stable conformer and first above it
increases for aqua-complex. It means that the
presence of the water molecule additionally
stabilizes complex. Cu(Me2Val)2 in CD3OD shows
more complicated dependence of ?? to ?/T. Since
it is not linear (i.e. the volume of the complex
changes in temperature interval examined), there
are some conformational changes. The energy
difference between the most stable conformer and
first above it is smaller when water molecule is
present which allows us to suggest some
rearrangements of amino acid side chains and
perhaps releasing of apical ligand (water) during
the heating.
Cu(Me2Leu)24H2O
Ow
Figure 4. The most stable conformations
of aqua-complexes of Cu(Me2Leu)2 and Cu(Me2Val)2
with both side chains in axial positions.
Cu(Me2Val)2 4H20
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