D=jo701636bn00001> |
The interaction of a synthetic enantiopure azamacrocyclic receptor (
L) with biologically important chiral
dicarboxylates (A,
1-
7) has been stu
die
d by means of potentiometric titrations in 0.15 M NaCl aqueoussolution in a wi
de pH range. This macrocycle forms strong complexes of the type [H
nLA]
(n-2) (with
n =0-5). As a general tren
d, the bin
ding is much tighter at basic or neutral pH than in aci
dic me
dium.Interestingly, nonprotecte
d excitatory amino aci
ds (Asp an
d Glu) are strongly boun
d even at aci
dic pH.Regar
ding selectivity, the receptor showe
d stereoselective bin
ding towar
d those substrates bearing anH-bon
ding
donor at C
, being
S-selective in most of the cases, except for glutamic aci
d. Thus,
L displaye
dan excellent enantioselectivity for (
S)-malate
dianion (
KS/
KR = 11.50 at pH 10.0 an
d KS/
KR = 6.86 at pH7.0) an
d exhibite
d mo
derate enantiopreference for (
S,
S)-tartrate (
KSS/
KRR = 3.01 at pH 10 an
d KSS/
KRR= 1.70 at pH 7.0). For this last anion, a very goo
d diastereopreference was also observe
d (
KSS/
KRS =8.46 at pH 10 an
d KSS/
KRS = 4.99 at pH 7.0). On the contrary,
L is smoothly
R-selective towar
d (
R)-Glu(
KR/
KS = 3.22 at pH 10 an
d KR/
KS = 2.05 at pH 7.0)
due to its longer an
d more flexible molecularstructure. The stereoselectivity of the correspon
ding complexes
decrease
d when
decreasing pH values.For the hy
droxy
derivatives, mass spectrometry also reflecte
d the tren
ds observe
d by potentiometry an
dconfirme
d the receptor:
dicarboxylate 1:1 stoichiometry of the supramolecular complexes. A
dditionalexperimental techniques were use
d to stu
dy the most stereoselective example. Solution stu
dies by NMRsuggeste
d a goo
d geometrical complementarity between the malate
dianion an
d the receptor, which showe
da pre
dominant helical conformation in solution. Besi
des, self-
diffusion rates (PGSE) of the
diastereomericcomplexes with malate also agree with bin
ding
data. Circular
dichroism was also use
d in this case at
different pH values, showing a very goo
d correlation between the helical content of the receptor an
d thestereoselectivity of the molecular recognition process.