- Email: [email protected]
Crystal and molecular structure of the tetramorpholino derivative of the cyclophosphazenic SPIRO (30203) species, a radiopaques precursor
Journal of Molecular Structure, 269 (1992) 355-365 Elsevier Science Publishers B.V., Amsterdam
355
Crystal and molecular structure of the tetramorpholino derivative of the cyclophosphazenic SPIRO (30203)* species, a radiopaques precursor Renee Enjalbert”, Jean Galy”, Sylvie Scheideckerb, Delphine Semenzinb, Jean-Pierre Bonnetb, Francois Sourniesb and Jean-Francois Labarreb “Centre d%laboration des Mate’riaux et d’Etudes Structurales du CNRS, 29, Rue Jeanne Marvig, BP 4347, 31055 Toulouse Cedex (France) bLaboratoire Structure et Vie de 1’Universite Paul Sabatier, 118, Route de Narbonne, 31062 Toulouse Cedex (France) (Received 18 December 1991)
Abstract Peraminolysis of the cyclophosphazenic SPIRO (30203) chlorinated cryptand by morpholine leads to the tetramorpholino derivative SPIRO (30203)(Morph,). This compound crystallizes in the triclinic system, Pi, with a = 12.99(3), b = 13.06(Z), c = 12.47(3) A, tl = 1191(l), b = 117.3(l), y = 82,6(Z)‘, V = 1637(7) A3, p, = 1.32(6) Mgme3, 2 = 2 and R = 0.049 for 2792 unique reflections and 379 variable parameters. The two geminal pairs of morpholino moieties are symmetrical versus one two-fold axis of the molecule and their nitrogen atoms are noticeably non-planar. The HNndash;(CH,),-O-(CH,),-O-(CH,),-NH loop adopts a chistera-like conformation which is prone to metal recognition for radiopaques design.
INTRODUCTION
Reactions of long-chain oxodiamines with hexachlorocyclotriphosphazene, N, P, Cl,, lead to macrocyclic host molecules, whose conformation, cavity size and number of coordination sites depend drastically on experimental conditions [l-11]. Most of these attractive one- and two-ring architectures were unambiguously detected by X-ray investigations [S-11], but to date only four configurations have been observed: (i) the SPIRO configuration (in which the oxodiamino ligand is grafted as a SPIRO loop onto one phosphorus atom of one N,P, ring); (ii) the cis-ANSA configuration (in Correspondence to: Professor J-F. Labarre, Laboratoire Structure et Vie de 1’Universit.e Paul Sabatier, 118 Route de Narbonne, 31662 Toulouse Cedex, France. * For nomenclature, see F. Sournies, P. Castera, A. El Bakili and J-F. Labarre, J. Mol. Struct., 221 (1990) 239.
OOZZ-2860/92/$05.00 0 1992 Elsevier Science Publishers
B.V. All rights reserved.
356 which the oxodiamino ligand is grafted on one side of one N,P, ring as an ANSA arch onto two different phosphorus atoms); (iii) the trans-ANSA configuration (in which the oxodiamino ligand is grafted on both sides of one N,P, ring as an ANSA arch onto two different phosphorus atoms); (iv) the BIN0 configuration (in which the oxodiamino ligand bridges two different N3P, rings). We recently reported [12] the possibility of using one of these new macrocyclic compounds, namely the SPIRO (30203) (1)[3,6] obtained from H,N(CH,),-O-(CH,),-0-(CH,),-NH, , as a cryptand for monovalent lithium (la), divalent zinc (lb) and magnesium (1~). These three molecular structures reveal three different patterns of metal coordination. In compound (la), one of the two hydrogen atoms in SPIRO 30203 is substituted by lithium generating a dimeric structure with pentacoordinated lithium centres. This structure is further stabilized by N-H hydrogen bonds. In (lb), both hydrogen atoms of the macrocyclic loop are replaced by two zinc atoms through a cross-link metallation leading again to a dimeric molecule. In this compound, the zinc atom is found to be in a trigonal bipyramidal environment with one very long-range N-Zn interaction. The origin of the dimerization of the magnesium compound (lc)is analogous to (lb). Magnesium is in the centre of a distorted octahedron, coordinated with the O- and N-donors of the macrocyclic loop and also with one nitrogen atom of the N3P3ring. (lc)is the first example of a metallic centre coordinated by a neutral phosphazene ligand. Aluminium cryptates were also obtained from SPIRO (30203) as the cryptands [13], which reveal another pattern of metal coordination, where the two hydrogen atoms in SPIRO (30203) are substituted by aluminium for generating monomeric structures with pentacoordinated aluminium centres in the inner cavities. Thus, cyclophosphazenic cryptands such as SPIRO (30203) are capable of metal recognition for cryptate generation. However, such chlorinated cryptates are useless for biological applications because of (i) their very poor solubility in physiological serum and (ii) their irnmunodepressive behaviour due to chlorine atoms. We were, therefore, encouraged to design new cyclophosphazenic cryptands which would generate highly soluble and non-immunodepressive cryptates. Within this framework, we attempted the production of peraminocryptands through peraminolysis of chlorinated cyclophosphazenic cryptands. Several SPIRO (30203) X4 peramino derivatives with X = piperidino, piperazino, pyrrolidino and morpholino groups were prepared, and this paper reported on the crystal and molecular structure of the tetramorpholino derivative, SPIRO (30203) (Morph,).
357 TABLE 1 Physical properties and parameters for data collection and refinement Formula Mol. wt. (g) Crystal system Space group a (A) b (A) c (A) a (deg) B (deg) Y (ded v (8”) z
P,W,W%,
653.7 Triclinic
Pi
1 (A) Take-off (deg) Detector width (mm) Scan type Scan width (deg) %range (deg) No. of measured reflections No. of unique reflections NO No. of variables, NV
12.90(3) 13&i(2) 12.47(3) 118.1(l) 117.3(l) 82.6(2) 1637(7) 2 1.32(6) 1.31(2) 700 2.3 293 0.71069 3.6 4x4 812% 0.60 + 0.35 tan% &22 4349 2792 (I 2 30) 379
Agreement factors R
0.049
he (tzcm-3) kxp k cm-“) 8’ WV p (MO Ka) (cm-‘) Temperature (K)
0.054 1.3
R, S
X-RAY STUDY
Data collection A colourless single crystal (0.12 x 0.15 x 0.20mm) was chosen for data collection using an Enraf Nonius CAD4 diffractometer. 25 hkl reflections were used to refine the lattice parameters (Table 1). Details of data collection are reported in Table 1. Lorentz and polarization corrections were applied but absorption corrections were not necessary. Structural
analysis
and refinement
The structure was determined using direct methods leading to the
location of all non-hydrogen atoms. All hydrogen atoms were then evidenced from the difference Fourier map, but they were added to the structure factors calculations (for consistency with our previous X-ray structures within the series [E&11]) as fixed at 1.08A from their relative attached atoms. Scattering factors were taken from Cromer and Waber [14] and anomalous dispersion effects from Cromer and Liberman [15]. Details for refinement are summarized in Table 1. Both calculations with SHELX 813[16] and illustrations with ORTEP 1171software were performed on an ALLIANT VFX 80 computer. RESULTS
Final positions and equivalent isotropic thermal parameters for the 42 non-hydrogen independent atoms are given in Table 2. Fractional coordinates of related hydrogen atoms are listed in Table 3. Bond lengths and angles are given in Tables 4 and 5 respectively. DISCUSSION
Two ball-and-stick drawings of suitable perspective views of the title molecule are given in Figs. 1 and 2 (the hydrogen numbering is omitted for clarity). The most striking features from these pictures are the following. (i) A quasi two-fold symmetry exists at the level of the four morpholino ligands with respect to the N(2) -* +P(1) direction. (ii) These ligands all adopt a chair conformation with one of them, namely the N(9)-C(21)-C(22)-0(6)-C(23)-C(24) ligand, being slightly more flattened than the others. Indeed, the distances from N(9) and O(6) to the C(21), C(22), C(23) and C(24) plane are + 0.49(5) A, whereas the distances from N(6), N(7) and N(8) to their relative carbon planes are all equal to f 0.64(5) A. Moreover, the exocyclic N(6), N(7) and N(8) atoms are not strictly planar, the sum of their related angles being noticeably less than 360’ (346.1’ on N(6), 345.6’ on N(7) and 350.2’ on N(8)). Conversely, the N(9) atom looks quite planar, the sum of its related angles (357.8’) being very close to 360’ (Table 5). (iii) Such a two-fold symmetry would normally imply that the SPIRO loop is unfolded into the (TVplane containing the N(2). * * P(1) C, axis, as is observed in the chlorinated starting material SPIRO (30203) [6]. Actually, the SPIRO loop of the title molecule adopts a serendipitous “chistera-like” conformation (i.e. shaped as the gauntlet used when playing Basque pelota), which deserves special attention. An extensive survey of intramolecular contacts shows that this chistera-like conformation is due to a strong intramolecular N(5)H(5) * . . O(1) hydrogen bond (H(5). . *O(1) = 2.212(S)& N(5)-H(5)-O(1) = 162.2(4)‘) related to the N(5)-H(5) hydrogen
TABLE 2 Positional parameters and equivalent isotropic thermal factors for non-hydrogen atoms of the title molecule Atom
xla
Pl
0.2529(l) 0.2317(l) 0.1207(l) 0.4218(4) 0.5956(4) 0.5597(5) 0.0251(4) 0.1915(4) -0.2672(4) 0.2651(4) 0.1572(4) 0.1798(4) 0.2005(4) 0.3758(4) 0.3554(4) 0.1581(4) 0.1434(4) - 0.0225(4) 0.1883(5) 0.2190(6) 0.3400(7) 0.5391(7) 0.6184(6) 0.5166(6) 0.4854(6) 0.4465(5) 0.3487(6) 0.4580(8) 0.5662(6) 0.4609(5) 0.2062(5) 0.1482(7) -0.0214(6) 0.0304(6) 0.2386(5) 0.2089(6) 0.0981(6) 0.1238(6) - 0.0999(6) -0.2156(7) -0.1925(6) -0.0778(6)
P2 P3 01 02 03 04 05 06
Nl N2 N3 N4 N5 N6 N7 N8 N9 Cl c2 c3 c4 c5 C6 c7 C8 c9 Cl0 Cl1 Cl2 Cl3 Cl4 Cl5 Cl6 Cl7 Cl8 Cl9 c20 c21 c22 C23 C24
0.7477(l) 0.7829(l) 0.5818(l) 0.8774(4) 0.7395(5) 0.7660(5) 1.0513(4) 0.2162(4) 0.5549(5) 0.8274(4) 0.65&I(4) 0.6228(4) 0.8310(4) 0.7231(4) 0.7936(4) 0.8760(4) 0.4463(4) 0.5650(4) 0.7993(5) 0.9008(6) 0.9612(6) 0.9239(7) 0.8279(9) 0.6433(7) 0.5666(S) 0.6299(s) 0.7522(6) 0.7960(8) 0.8072(7) 0.7608(6) 0.9995(5) 1.0612(6) 0.9318(6) 0.8674(6) 0.4227(5) 0.3033(6) 0.2398(5) 0.3575(5) 0.5281(7) 0.4888(g) 0.5894(8) 0.6323(8)
zlc
u, (A’)
0.3573(2) 0.5867(2) 0.3415(2) 0.2262(4) 0.3276(5) 0.9241(5) 0.7631(6) 0.2656(5) 0.1029(5) 0.5070(4) 0.5000(5) 0.2793(4) 0.2821(5) 0.3462(5) 0.7213(4) 0.6652(5) 0.3175(4) 0.2446(5) 0.1485(6) 0.1395(7) 0.2435(8) 0.3203(8) O-3016(8) 0.2088(7) 0.2511(7) 0.3607(7) 0.8079(7) 0.9406(8) 0.8399(7) 0.7036(6) 0.7505(7) 0.8389(8) 0.6822(g) 0.5874(7) 0.4223(6) 0.3978(7) 0.1644(6) 0.1817(6) 0.2781(7) 0.170(l) 0.0697(8) 0.1728(9)
0.031(l) 0.034(2) 0.033(2) 0.053(5) 0.058(6) 0.071(7) 0.062(6) 0.057(6) O.OSO(6) 0.035(5) 0.037(5) 0.034(5) 0.036(5) 0.039(5) 0.038(5) 0.037(5) 0.035(5) 0.037(5) 0.042(7) 0.049(8) 0.057(9) 0.06(l) 0.06(l) 0.054(8) 0.056(8) 0.050(8) 0.055(8) 0.07(l) 0.062(9) 0.048(7) 0.048(7) 0.060(S) 0.06(l) 0.057(8) 0.045(7) 0.051(8) 0.051(8) 0.046(7) 0.054(9) 0.08(l) 0.06(l) 0.07(l)
360 TABLE 3 Fractional coordinates of hydrogen atoms for the title molecule Atom
xla
y/b
s/c
Atom
H4 H5 Hll H21 H12 H22 H13 H23 H14 H24 H15 H25 H16 H26 H17 H27 H18 H28 H19 H29 HllO H210 Hlll H211 H112
0.174 0.408 0.245 0.098 0.157 0.212 0.348 0.357 0.563 0.548 0.708 0.606 0.438 0.558 0.415 0.562 0.523 0.395 0.274 0.339 0.453 0.463 0.572 0.644 0.456
0.914 0.781 0.733 0.764 0.963 0.870 0.996 1.031 0.989 0.963 0.867 0.788 0.674 0.595 0.501 0.525 0.667 0.568 0.783 0.658 0.759 0.890 0.901 0.780 0.667
0.335 0.326 0.126 0.074 0.154 0.039 0.345 0.229 0.304 0.423 0.371 0.198 0.154 0.144 0.162 0.288 0.459 0.356 0.827 0.757 1.090 0.994 0.890 0.826 0.651
H212 H113 H213 H114 H214 H115 H215 H116 H216 H117 H217 H118 H218 Hll9 H219 H120 H220 H121 H221 H122 H222 H123 H223 H124 H224
x/a
-
-
0.468 0.299 0.191 0.182 0.168 0.002 0.115 0.010 0.005 0.319 0.249 0.129 0.280 0.086 0.019 0.050 0.201 0.103 0.665 0.271 0.214 0.230 0.188 0.025 0.079
ylb 0.797 1.006 1.039 1.152 1.024 0.893 0.926 0.904 0.777 0.425 0.488 0.303 0.284 0.173 0.239 0.375 0.358 0.601 0.458 0.484 0.402 0.657 0.514 0.636 0.720
0.644 0.813 0.686 0.898 0.907 0.748 0.624 0.520 0.528 0.417 0.522 0.406 0.473 0.065 0.173 0.106 0.169 0.366 0.302 0.212 0.095 0.041 - 0.017 0.127 0.246
atom pointing towards the inner cavity of the loop. Incidentally, this hydrogen bond is responsible for the short intramolecular contact which exists between N(5)-H(5) and O(2) (H(5). . . O(2) = 2.410(8) & N(5)-H(5)-O(2) = 112.2(4)0). Moreover, a strong intermolecular N(4)-H(4). * - O(4) interaction (H(4) *. . O(4) = 2.374(8) A, N(4)-H(4b0(4) = 119.3(4)‘) exists between the N(4)-H(4) hydrogen atom which points towards the outside of the loop and one oxygen atom, namely O(4i) (with i defined from -x, 2 - y, 1 - z symmetry operations) of an adjacent molecule in unit packing cell (Fig. 3). Thus, there is no intramolecular hydrogen bond between N(4)-H(4) and O(l), O(2), both N(4). . *O(1) and N(4) * . . O(2) distances being larger than 3.5 A. X-ray studies provide an understanding of the way the SPIRO loop is grafted onto the cyclophosphazenic ring in the title molecule. The free H,N-(CH,),-O--(CH,),-O-(CH,)sNH, oxodiamine adopts a sort of “ball of wool” conformation because of intramolecular hydrogen bonds between terminal NH, groups and their nearest oxygen atoms, N. . *0 distances (as
361 TABLE 4 Bond lengths (A) in the title molecule Atom 1
P(l) P(1) P(l) P(l) P(2) P(2) P(2) P(2) P(3) P(3) P(3) P(3) O(l) O(1) O(2) O(2) O(3) O(3) O(4) O(4) O(5) O(5) O(6) O(6)
Atom 2
Distance (A)
Atom 1
Atom 2
Distance (A)
NW
1.592(6) 1.598(7) l&46(7) 1.633(7) 1.585(7) 1.591(7) 1.663(6) 1.665(7) 1.592(6) 1.583(7) 1.660(7) 1.652(7) 1.43(l) 1.40(l) 1.43(l) 1.41(l) 1.40(l) 1.42(l) 1.41(l) 1.42(l) 1.42(l) 1.42(l) 1.38(l) 1.40(l)
N(4) N(5) N(6) N(6) N(7) N(7) N(8) N(8) N(9) N(9) C(1) C(2) C(4) C(6) C(7) C(9) Wl) C(l3) W5) C(l7) C(l9) C(21) c(23)
C(l) C(8) C(9)
1.45(l) 1.45(l) 1.45(l) 1.45(l) 1.46(l) 1.46(l) 1.45(l) 1.45(l) 1.45(l) 1.44(l) 1.50(l) 1.50(l) 1.51(l) 1.50(l) 1.50(l) 1.49(l) 1.49(l) 1.48(l) 1.48(l) 1.51(l) 1.51(l) 1.42(l) 1.40(l)
N(3) N(4) N(5) N(l) N(2) N(6) N(7) N(2) N(3) N(8) N(9) C(3) C(4) C(5) C(6) COO) C(l1) C(l4) C(l5) C(18) C(l9) C(22) c(23)
cw
W3) C(l6) C(l7) C(20) C(21) c(24) C(2) C(3) C(5) C(7) C(8) C(lO) C(l2) C(l4) C(l6) C(l8) C(20) C(22) c(24)
well as the 0 **.O one) being around 2.90 Hi.What happens now when such a “daisy-like” folded architecture is going to attack the cyclophosphazenic ring on one of its phosphorus atoms? The real mechanism of this dinucleophilic attack is elucidated through Figs. 1 and 2; an amino function of the oxodiamine, namely the one corresponding to N(5), is firstly grafted onto P(1) and the chain keep its “daisy-like” folded conformation as far as the O(1) atom, leaving N(5) * *. O(2) and O(2) *. . O(1) equal to 3.26 and 2.89A respectively; these distances are very close to their value (2.90& in the free oxodiamine. The second amino function has to link the same P(1) atom, trying again to keep N(4) 0. * O(1) equal to 2.90A. This would be possible if the N(4). . . N(5) distance were also about 2.90 Hi, but its actual value (2.55 A) is too short for an unconstrained closure of the loop, the original N(4)-H(4) * *. O(1) hydrogen bond then being broken, as shown in Figs. 1 and 2 (N(4)-H(4) points towards the outside of the loop with N(4). **O(1) larger than 3.5 A). Then, the N(4)-H(4) “out-of-loop” hydrogen atom may interact with some external coordination site, i.e. in the present
362 TABLE 5 Bond angles (deg) in the title molecule Atom 1
Atom 2
Atom 3
Angle (deg)
Atom
NW N(1) NW
P(l)
N(3) N(4) N(5) N(4) N(5) N(5) N(2) N(6) N(7) N(6) N(7) N(7) N(3) N(8) N(9) N(8) N(9) N(9) C(4) C(6) C(ll) C(l5) C(l9) c(23) P(2) P(3) P(3) C(l) C(8) C(9) C(l2) C(l2) C(l3)
114.0(3) 104.2(3) 115.8(3) 115.8(3) 106.4(4) 100.1(4) 116.8(3) 107.0(3) 112.4(4) 113.1(4) 106.3(4) 100.0(3) 117.5(3) 105.5(3) 112.8(4) 112.6(4) 106.6(3) 100.6(3) 113.4(7) 113.5(6) 110.6(7) 110.0(7) 110.0(6) 112.9(8) 124.6(4) 121.1(4) 123.8(3) 123.6(5) 126.1(5) 117.6(5) 118.2(4) 110.3(6) 117.9(5)
P(2)
N(3) N(3) N(4) N(1) N(l) N(1) N(2) N(2) N(6) N(2) N(2) N(2) N(3) N(3) N(8) C(3) C(5) C(lO) C(l4) C(l8) C(22) P(l) P(2) P(1) P(1) P(1) P(2) P(2) C(9) P(2)
pm P(l) P(l) PO) P(l) P(2) P(2) P(2) P(2) P(2) P(2) P(3) P(3) P(3) P(3) P(3) P(3) O(l) O(2) O(3) O(4) O(5) O(6) N(1) N(2) N(3) N(4) N(5) N(6) N(6) N(6) N(7)
C(13) P(3) P(3) C(l7) P(3) P(3) C(21) N(4) C(l) O(l) O(l) O(2) O(2) C(6) N(5) N(6) O(3) O(3) N(6) N(7) O(4) O(4) N(7) N(8) O(5) O(5) N(8) N(9) O(6i O(6) N(9)
2 N(7) N(7) N(8) N(8) N(8) N(9) N(9) N(9) C(1) C(2) C(3) C(4) C(5) C(6) C(7) C(8) C(9) C(lO) C(l1) C(l2) C(l3) C(l4) C(l5) C(l6) C(l7) C(l8) C(l9) C(20) C(21) C(22) c(23) c(24)
Atom 3
Angle (deg)
W3 CW
118.3(5) 109.4(6) 121.4(4) 117.6(5) 111.2(6) 118.9(5) 122.3(6) 112.6(7) 112.8(6) 113.8(7) 108.2(7) 109.8(7) 113.0(8) 108.4(6) 114.5(7) 113.0(7) 110.1(7) 112.8(7) 111.7(7) 109.6(6) 109.6(7) 112.3(7) 110.9(8) 109.7(6) 108.5(6) 111.0(6) 111.1(6) 108.8(6) 112.9(7) 118.0(l) 115.8(8) 115.5(9)
C(l7) C(20) C(20) C(21) c(24) c(24) C(2) C(3) C(2) C(5) C(4) C(7) C(8) C(7) C(lO) C(9) C(l2) C(l1) C(l4) C(l3) C(l6) C(l5) C(l8) C(l7) C(20) C(l9) C(22) C(21) c(24) c(23)
case, with an O(4) atom from an adjacent molecule. Therefore, we may conclude that the dinucleophilic attack of N,P,C& occurs through a twostep procedure and not in a bimolecular concerted way. Another striking feature comes from the uncommonly severe lack of planarity of the N,P, ring in the title molecule. Indeed, the N(1) atom deviates by 0.20 A from the P(l)-N(3)-P(3)-N(2)-P(2) plane towards the N(4) exocyclic nitrogen atom. This situation is due to the noticeable distortion of the loop (Fig. 1) with respect to the cyclophosphazenic ring; seven atoms, N(5), C(8), C(7), C(6), O(2), C(5) and C(4), are below this plane whereas only
363
Fig. 1. A perspective view of the title molecule with numbering of atoms and the N,P, ring perpendicular to the plane of the figure (slightly tilted for clarity).
four atoms, N(4), C(l), C(2) and C(3), are above it (O(1) belongs to the cyclophosphazenic plane). Such a dissymmetry, which makes the lower part of the SPIRO loop more bulky than its upper part, pushes the closest endocyclic nitrogen atom, N(l), outside of the N,P, ring towards the less hindered part of the molecular space. CONCLUSION
The molecular structure of the title compound reveals a surprising “chisteralike” conformation of its SPIRO loop due to strong intra- and intermolecular hydrogen bonds. Such a peculiar conformation makes this loop prone to metal recognition according to the fact that insertion of hard metals (lithium, zinc, magnesium and aluminium) in the inner cavity of SPIRO (30203) leads to SPIRO loops which adopt precisely “chistera-like” conformations. Thus, we may predict that the title molecule will be capable of accepting metals such as calcium, gadolinium, hafnium and europium for further radiopaques design. Moreover, since peramino derivatives of
364
bC14
b
Fig. 2. A perspective view of the title molecule with the N,P, ring parallel to the plane of the figure (slightly tilted for clarity).
Fig. 3. A perspective view of the molecular packing.
365
SPIRO (30203), such as the title compound, are (i) highly soluble in physiological serum and (ii) poorly immunodepressive, we may expect that their metallated cryptates will be suitable for many biological applications. REFERENCES
2 3 4 5 6 7
8 9
10 11 12 13 14 15 16 17
F. Sournies, P. Castera, A. El Bakili and J-F. Labarre, J. Mol. Struct., 221 (1990) 239. F. Sournies, P. Castera, J-P. Faucher, M. Graffeuil and J-F. Labarre, J. Mol. Struct., 221 (1990) 245. A. El Bakili, P. Castera, J-P. Faucher, F. Sournies and J-F. Labarre, J. Mol. Struct., 195 (1989) 21. F. Sournies, A. El Bakili, J-F. Labarre and B. Perly, J. Mol. Struct., 196 (1989) 201. F. Sournies, A. El Bakili, B. Zanin, J-F. Labarre and J. Jaud, J. Mol. Struct., 220 (1990) 43. R. Enjalbert, J. Galy, A. El Bakili, P. Castera, J-P. Faucher, F. Sournies and J-F. Labarre, J. Mol. Struct., 196 (1989) 207. T.S. Cameron, A. Linden, F. Sournies, A. El Bakili and J-F. Labarre, J. Mol. Struct., 197 (1989) 41. T.S. Cameron, A. Linden, A. El Bakili, P. Castera, J-P. Faucher, M. Graffeuil, F. Sournies and J-F. Labarre, J. Mol. Struct., 212 (1989) 281. J. Jaud, F. Sournies and JF. Labarre, J. Mol. Struct., 212 (1989) 305. R. Enjalbert, J. Galy, F. Sournies and J-F. Labarre, J. Mol. Struct., 221 (1990) 53. R. Enjalbert, J. Galy, B. Zanin, J-P. Bonnet, F. Sournies and J-F. Labarre, J. Mol. Struct., 246 (1991) 123. M. Veith, M. Kross and J-F. Labarre, J. Mol. Struct., 243 (1991) 189. M. Veith, M. Kross and J-F. Labarre, J. Mol. Struct., 248 (1991) 345. D.T. Cromer and J.T. Waber, International Tables for X-Ray Crystallography, Vol. IV, Kynoch Press, Birmingham, 1974, Table 2.2 A. D.T. Cromer and D. Liberman, International Tables for X-Ray Crystallography, Vol. IV, Kynoch Press, 1974, Birmingham, Table 2.3.1. G. Sheldrick, Program for Crystal Structure Determination, Version SHELX-86, Oxford University Press, Cambridge, 1986. C.K. Johnson, ORTEP II,Report ORNL-5138, Oak Ridge National Laboratory, TN, 1976.
355
Crystal and molecular structure of the tetramorpholino derivative of the cyclophosphazenic SPIRO (30203)* species, a radiopaques precursor Renee Enjalbert”, Jean Galy”, Sylvie Scheideckerb, Delphine Semenzinb, Jean-Pierre Bonnetb, Francois Sourniesb and Jean-Francois Labarreb “Centre d%laboration des Mate’riaux et d’Etudes Structurales du CNRS, 29, Rue Jeanne Marvig, BP 4347, 31055 Toulouse Cedex (France) bLaboratoire Structure et Vie de 1’Universite Paul Sabatier, 118, Route de Narbonne, 31062 Toulouse Cedex (France) (Received 18 December 1991)
Abstract Peraminolysis of the cyclophosphazenic SPIRO (30203) chlorinated cryptand by morpholine leads to the tetramorpholino derivative SPIRO (30203)(Morph,). This compound crystallizes in the triclinic system, Pi, with a = 12.99(3), b = 13.06(Z), c = 12.47(3) A, tl = 1191(l), b = 117.3(l), y = 82,6(Z)‘, V = 1637(7) A3, p, = 1.32(6) Mgme3, 2 = 2 and R = 0.049 for 2792 unique reflections and 379 variable parameters. The two geminal pairs of morpholino moieties are symmetrical versus one two-fold axis of the molecule and their nitrogen atoms are noticeably non-planar. The HNndash;(CH,),-O-(CH,),-O-(CH,),-NH loop adopts a chistera-like conformation which is prone to metal recognition for radiopaques design.
INTRODUCTION
Reactions of long-chain oxodiamines with hexachlorocyclotriphosphazene, N, P, Cl,, lead to macrocyclic host molecules, whose conformation, cavity size and number of coordination sites depend drastically on experimental conditions [l-11]. Most of these attractive one- and two-ring architectures were unambiguously detected by X-ray investigations [S-11], but to date only four configurations have been observed: (i) the SPIRO configuration (in which the oxodiamino ligand is grafted as a SPIRO loop onto one phosphorus atom of one N,P, ring); (ii) the cis-ANSA configuration (in Correspondence to: Professor J-F. Labarre, Laboratoire Structure et Vie de 1’Universit.e Paul Sabatier, 118 Route de Narbonne, 31662 Toulouse Cedex, France. * For nomenclature, see F. Sournies, P. Castera, A. El Bakili and J-F. Labarre, J. Mol. Struct., 221 (1990) 239.
OOZZ-2860/92/$05.00 0 1992 Elsevier Science Publishers
B.V. All rights reserved.
356 which the oxodiamino ligand is grafted on one side of one N,P, ring as an ANSA arch onto two different phosphorus atoms); (iii) the trans-ANSA configuration (in which the oxodiamino ligand is grafted on both sides of one N,P, ring as an ANSA arch onto two different phosphorus atoms); (iv) the BIN0 configuration (in which the oxodiamino ligand bridges two different N3P, rings). We recently reported [12] the possibility of using one of these new macrocyclic compounds, namely the SPIRO (30203) (1)[3,6] obtained from H,N(CH,),-O-(CH,),-0-(CH,),-NH, , as a cryptand for monovalent lithium (la), divalent zinc (lb) and magnesium (1~). These three molecular structures reveal three different patterns of metal coordination. In compound (la), one of the two hydrogen atoms in SPIRO 30203 is substituted by lithium generating a dimeric structure with pentacoordinated lithium centres. This structure is further stabilized by N-H hydrogen bonds. In (lb), both hydrogen atoms of the macrocyclic loop are replaced by two zinc atoms through a cross-link metallation leading again to a dimeric molecule. In this compound, the zinc atom is found to be in a trigonal bipyramidal environment with one very long-range N-Zn interaction. The origin of the dimerization of the magnesium compound (lc)is analogous to (lb). Magnesium is in the centre of a distorted octahedron, coordinated with the O- and N-donors of the macrocyclic loop and also with one nitrogen atom of the N3P3ring. (lc)is the first example of a metallic centre coordinated by a neutral phosphazene ligand. Aluminium cryptates were also obtained from SPIRO (30203) as the cryptands [13], which reveal another pattern of metal coordination, where the two hydrogen atoms in SPIRO (30203) are substituted by aluminium for generating monomeric structures with pentacoordinated aluminium centres in the inner cavities. Thus, cyclophosphazenic cryptands such as SPIRO (30203) are capable of metal recognition for cryptate generation. However, such chlorinated cryptates are useless for biological applications because of (i) their very poor solubility in physiological serum and (ii) their irnmunodepressive behaviour due to chlorine atoms. We were, therefore, encouraged to design new cyclophosphazenic cryptands which would generate highly soluble and non-immunodepressive cryptates. Within this framework, we attempted the production of peraminocryptands through peraminolysis of chlorinated cyclophosphazenic cryptands. Several SPIRO (30203) X4 peramino derivatives with X = piperidino, piperazino, pyrrolidino and morpholino groups were prepared, and this paper reported on the crystal and molecular structure of the tetramorpholino derivative, SPIRO (30203) (Morph,).
357 TABLE 1 Physical properties and parameters for data collection and refinement Formula Mol. wt. (g) Crystal system Space group a (A) b (A) c (A) a (deg) B (deg) Y (ded v (8”) z
P,W,W%,
653.7 Triclinic
Pi
1 (A) Take-off (deg) Detector width (mm) Scan type Scan width (deg) %range (deg) No. of measured reflections No. of unique reflections NO No. of variables, NV
12.90(3) 13&i(2) 12.47(3) 118.1(l) 117.3(l) 82.6(2) 1637(7) 2 1.32(6) 1.31(2) 700 2.3 293 0.71069 3.6 4x4 812% 0.60 + 0.35 tan% &22 4349 2792 (I 2 30) 379
Agreement factors R
0.049
he (tzcm-3) kxp k cm-“) 8’ WV p (MO Ka) (cm-‘) Temperature (K)
0.054 1.3
R, S
X-RAY STUDY
Data collection A colourless single crystal (0.12 x 0.15 x 0.20mm) was chosen for data collection using an Enraf Nonius CAD4 diffractometer. 25 hkl reflections were used to refine the lattice parameters (Table 1). Details of data collection are reported in Table 1. Lorentz and polarization corrections were applied but absorption corrections were not necessary. Structural
analysis
and refinement
The structure was determined using direct methods leading to the
location of all non-hydrogen atoms. All hydrogen atoms were then evidenced from the difference Fourier map, but they were added to the structure factors calculations (for consistency with our previous X-ray structures within the series [E&11]) as fixed at 1.08A from their relative attached atoms. Scattering factors were taken from Cromer and Waber [14] and anomalous dispersion effects from Cromer and Liberman [15]. Details for refinement are summarized in Table 1. Both calculations with SHELX 813[16] and illustrations with ORTEP 1171software were performed on an ALLIANT VFX 80 computer. RESULTS
Final positions and equivalent isotropic thermal parameters for the 42 non-hydrogen independent atoms are given in Table 2. Fractional coordinates of related hydrogen atoms are listed in Table 3. Bond lengths and angles are given in Tables 4 and 5 respectively. DISCUSSION
Two ball-and-stick drawings of suitable perspective views of the title molecule are given in Figs. 1 and 2 (the hydrogen numbering is omitted for clarity). The most striking features from these pictures are the following. (i) A quasi two-fold symmetry exists at the level of the four morpholino ligands with respect to the N(2) -* +P(1) direction. (ii) These ligands all adopt a chair conformation with one of them, namely the N(9)-C(21)-C(22)-0(6)-C(23)-C(24) ligand, being slightly more flattened than the others. Indeed, the distances from N(9) and O(6) to the C(21), C(22), C(23) and C(24) plane are + 0.49(5) A, whereas the distances from N(6), N(7) and N(8) to their relative carbon planes are all equal to f 0.64(5) A. Moreover, the exocyclic N(6), N(7) and N(8) atoms are not strictly planar, the sum of their related angles being noticeably less than 360’ (346.1’ on N(6), 345.6’ on N(7) and 350.2’ on N(8)). Conversely, the N(9) atom looks quite planar, the sum of its related angles (357.8’) being very close to 360’ (Table 5). (iii) Such a two-fold symmetry would normally imply that the SPIRO loop is unfolded into the (TVplane containing the N(2). * * P(1) C, axis, as is observed in the chlorinated starting material SPIRO (30203) [6]. Actually, the SPIRO loop of the title molecule adopts a serendipitous “chistera-like” conformation (i.e. shaped as the gauntlet used when playing Basque pelota), which deserves special attention. An extensive survey of intramolecular contacts shows that this chistera-like conformation is due to a strong intramolecular N(5)H(5) * . . O(1) hydrogen bond (H(5). . *O(1) = 2.212(S)& N(5)-H(5)-O(1) = 162.2(4)‘) related to the N(5)-H(5) hydrogen
TABLE 2 Positional parameters and equivalent isotropic thermal factors for non-hydrogen atoms of the title molecule Atom
xla
Pl
0.2529(l) 0.2317(l) 0.1207(l) 0.4218(4) 0.5956(4) 0.5597(5) 0.0251(4) 0.1915(4) -0.2672(4) 0.2651(4) 0.1572(4) 0.1798(4) 0.2005(4) 0.3758(4) 0.3554(4) 0.1581(4) 0.1434(4) - 0.0225(4) 0.1883(5) 0.2190(6) 0.3400(7) 0.5391(7) 0.6184(6) 0.5166(6) 0.4854(6) 0.4465(5) 0.3487(6) 0.4580(8) 0.5662(6) 0.4609(5) 0.2062(5) 0.1482(7) -0.0214(6) 0.0304(6) 0.2386(5) 0.2089(6) 0.0981(6) 0.1238(6) - 0.0999(6) -0.2156(7) -0.1925(6) -0.0778(6)
P2 P3 01 02 03 04 05 06
Nl N2 N3 N4 N5 N6 N7 N8 N9 Cl c2 c3 c4 c5 C6 c7 C8 c9 Cl0 Cl1 Cl2 Cl3 Cl4 Cl5 Cl6 Cl7 Cl8 Cl9 c20 c21 c22 C23 C24
0.7477(l) 0.7829(l) 0.5818(l) 0.8774(4) 0.7395(5) 0.7660(5) 1.0513(4) 0.2162(4) 0.5549(5) 0.8274(4) 0.65&I(4) 0.6228(4) 0.8310(4) 0.7231(4) 0.7936(4) 0.8760(4) 0.4463(4) 0.5650(4) 0.7993(5) 0.9008(6) 0.9612(6) 0.9239(7) 0.8279(9) 0.6433(7) 0.5666(S) 0.6299(s) 0.7522(6) 0.7960(8) 0.8072(7) 0.7608(6) 0.9995(5) 1.0612(6) 0.9318(6) 0.8674(6) 0.4227(5) 0.3033(6) 0.2398(5) 0.3575(5) 0.5281(7) 0.4888(g) 0.5894(8) 0.6323(8)
zlc
u, (A’)
0.3573(2) 0.5867(2) 0.3415(2) 0.2262(4) 0.3276(5) 0.9241(5) 0.7631(6) 0.2656(5) 0.1029(5) 0.5070(4) 0.5000(5) 0.2793(4) 0.2821(5) 0.3462(5) 0.7213(4) 0.6652(5) 0.3175(4) 0.2446(5) 0.1485(6) 0.1395(7) 0.2435(8) 0.3203(8) O-3016(8) 0.2088(7) 0.2511(7) 0.3607(7) 0.8079(7) 0.9406(8) 0.8399(7) 0.7036(6) 0.7505(7) 0.8389(8) 0.6822(g) 0.5874(7) 0.4223(6) 0.3978(7) 0.1644(6) 0.1817(6) 0.2781(7) 0.170(l) 0.0697(8) 0.1728(9)
0.031(l) 0.034(2) 0.033(2) 0.053(5) 0.058(6) 0.071(7) 0.062(6) 0.057(6) O.OSO(6) 0.035(5) 0.037(5) 0.034(5) 0.036(5) 0.039(5) 0.038(5) 0.037(5) 0.035(5) 0.037(5) 0.042(7) 0.049(8) 0.057(9) 0.06(l) 0.06(l) 0.054(8) 0.056(8) 0.050(8) 0.055(8) 0.07(l) 0.062(9) 0.048(7) 0.048(7) 0.060(S) 0.06(l) 0.057(8) 0.045(7) 0.051(8) 0.051(8) 0.046(7) 0.054(9) 0.08(l) 0.06(l) 0.07(l)
360 TABLE 3 Fractional coordinates of hydrogen atoms for the title molecule Atom
xla
y/b
s/c
Atom
H4 H5 Hll H21 H12 H22 H13 H23 H14 H24 H15 H25 H16 H26 H17 H27 H18 H28 H19 H29 HllO H210 Hlll H211 H112
0.174 0.408 0.245 0.098 0.157 0.212 0.348 0.357 0.563 0.548 0.708 0.606 0.438 0.558 0.415 0.562 0.523 0.395 0.274 0.339 0.453 0.463 0.572 0.644 0.456
0.914 0.781 0.733 0.764 0.963 0.870 0.996 1.031 0.989 0.963 0.867 0.788 0.674 0.595 0.501 0.525 0.667 0.568 0.783 0.658 0.759 0.890 0.901 0.780 0.667
0.335 0.326 0.126 0.074 0.154 0.039 0.345 0.229 0.304 0.423 0.371 0.198 0.154 0.144 0.162 0.288 0.459 0.356 0.827 0.757 1.090 0.994 0.890 0.826 0.651
H212 H113 H213 H114 H214 H115 H215 H116 H216 H117 H217 H118 H218 Hll9 H219 H120 H220 H121 H221 H122 H222 H123 H223 H124 H224
x/a
-
-
0.468 0.299 0.191 0.182 0.168 0.002 0.115 0.010 0.005 0.319 0.249 0.129 0.280 0.086 0.019 0.050 0.201 0.103 0.665 0.271 0.214 0.230 0.188 0.025 0.079
ylb 0.797 1.006 1.039 1.152 1.024 0.893 0.926 0.904 0.777 0.425 0.488 0.303 0.284 0.173 0.239 0.375 0.358 0.601 0.458 0.484 0.402 0.657 0.514 0.636 0.720
0.644 0.813 0.686 0.898 0.907 0.748 0.624 0.520 0.528 0.417 0.522 0.406 0.473 0.065 0.173 0.106 0.169 0.366 0.302 0.212 0.095 0.041 - 0.017 0.127 0.246
atom pointing towards the inner cavity of the loop. Incidentally, this hydrogen bond is responsible for the short intramolecular contact which exists between N(5)-H(5) and O(2) (H(5). . . O(2) = 2.410(8) & N(5)-H(5)-O(2) = 112.2(4)0). Moreover, a strong intermolecular N(4)-H(4). * - O(4) interaction (H(4) *. . O(4) = 2.374(8) A, N(4)-H(4b0(4) = 119.3(4)‘) exists between the N(4)-H(4) hydrogen atom which points towards the outside of the loop and one oxygen atom, namely O(4i) (with i defined from -x, 2 - y, 1 - z symmetry operations) of an adjacent molecule in unit packing cell (Fig. 3). Thus, there is no intramolecular hydrogen bond between N(4)-H(4) and O(l), O(2), both N(4). . *O(1) and N(4) * . . O(2) distances being larger than 3.5 A. X-ray studies provide an understanding of the way the SPIRO loop is grafted onto the cyclophosphazenic ring in the title molecule. The free H,N-(CH,),-O--(CH,),-O-(CH,)sNH, oxodiamine adopts a sort of “ball of wool” conformation because of intramolecular hydrogen bonds between terminal NH, groups and their nearest oxygen atoms, N. . *0 distances (as
361 TABLE 4 Bond lengths (A) in the title molecule Atom 1
P(l) P(1) P(l) P(l) P(2) P(2) P(2) P(2) P(3) P(3) P(3) P(3) O(l) O(1) O(2) O(2) O(3) O(3) O(4) O(4) O(5) O(5) O(6) O(6)
Atom 2
Distance (A)
Atom 1
Atom 2
Distance (A)
NW
1.592(6) 1.598(7) l&46(7) 1.633(7) 1.585(7) 1.591(7) 1.663(6) 1.665(7) 1.592(6) 1.583(7) 1.660(7) 1.652(7) 1.43(l) 1.40(l) 1.43(l) 1.41(l) 1.40(l) 1.42(l) 1.41(l) 1.42(l) 1.42(l) 1.42(l) 1.38(l) 1.40(l)
N(4) N(5) N(6) N(6) N(7) N(7) N(8) N(8) N(9) N(9) C(1) C(2) C(4) C(6) C(7) C(9) Wl) C(l3) W5) C(l7) C(l9) C(21) c(23)
C(l) C(8) C(9)
1.45(l) 1.45(l) 1.45(l) 1.45(l) 1.46(l) 1.46(l) 1.45(l) 1.45(l) 1.45(l) 1.44(l) 1.50(l) 1.50(l) 1.51(l) 1.50(l) 1.50(l) 1.49(l) 1.49(l) 1.48(l) 1.48(l) 1.51(l) 1.51(l) 1.42(l) 1.40(l)
N(3) N(4) N(5) N(l) N(2) N(6) N(7) N(2) N(3) N(8) N(9) C(3) C(4) C(5) C(6) COO) C(l1) C(l4) C(l5) C(18) C(l9) C(22) c(23)
cw
W3) C(l6) C(l7) C(20) C(21) c(24) C(2) C(3) C(5) C(7) C(8) C(lO) C(l2) C(l4) C(l6) C(l8) C(20) C(22) c(24)
well as the 0 **.O one) being around 2.90 Hi.What happens now when such a “daisy-like” folded architecture is going to attack the cyclophosphazenic ring on one of its phosphorus atoms? The real mechanism of this dinucleophilic attack is elucidated through Figs. 1 and 2; an amino function of the oxodiamine, namely the one corresponding to N(5), is firstly grafted onto P(1) and the chain keep its “daisy-like” folded conformation as far as the O(1) atom, leaving N(5) * *. O(2) and O(2) *. . O(1) equal to 3.26 and 2.89A respectively; these distances are very close to their value (2.90& in the free oxodiamine. The second amino function has to link the same P(1) atom, trying again to keep N(4) 0. * O(1) equal to 2.90A. This would be possible if the N(4). . . N(5) distance were also about 2.90 Hi, but its actual value (2.55 A) is too short for an unconstrained closure of the loop, the original N(4)-H(4) * *. O(1) hydrogen bond then being broken, as shown in Figs. 1 and 2 (N(4)-H(4) points towards the outside of the loop with N(4). **O(1) larger than 3.5 A). Then, the N(4)-H(4) “out-of-loop” hydrogen atom may interact with some external coordination site, i.e. in the present
362 TABLE 5 Bond angles (deg) in the title molecule Atom 1
Atom 2
Atom 3
Angle (deg)
Atom
NW N(1) NW
P(l)
N(3) N(4) N(5) N(4) N(5) N(5) N(2) N(6) N(7) N(6) N(7) N(7) N(3) N(8) N(9) N(8) N(9) N(9) C(4) C(6) C(ll) C(l5) C(l9) c(23) P(2) P(3) P(3) C(l) C(8) C(9) C(l2) C(l2) C(l3)
114.0(3) 104.2(3) 115.8(3) 115.8(3) 106.4(4) 100.1(4) 116.8(3) 107.0(3) 112.4(4) 113.1(4) 106.3(4) 100.0(3) 117.5(3) 105.5(3) 112.8(4) 112.6(4) 106.6(3) 100.6(3) 113.4(7) 113.5(6) 110.6(7) 110.0(7) 110.0(6) 112.9(8) 124.6(4) 121.1(4) 123.8(3) 123.6(5) 126.1(5) 117.6(5) 118.2(4) 110.3(6) 117.9(5)
P(2)
N(3) N(3) N(4) N(1) N(l) N(1) N(2) N(2) N(6) N(2) N(2) N(2) N(3) N(3) N(8) C(3) C(5) C(lO) C(l4) C(l8) C(22) P(l) P(2) P(1) P(1) P(1) P(2) P(2) C(9) P(2)
pm P(l) P(l) PO) P(l) P(2) P(2) P(2) P(2) P(2) P(2) P(3) P(3) P(3) P(3) P(3) P(3) O(l) O(2) O(3) O(4) O(5) O(6) N(1) N(2) N(3) N(4) N(5) N(6) N(6) N(6) N(7)
C(13) P(3) P(3) C(l7) P(3) P(3) C(21) N(4) C(l) O(l) O(l) O(2) O(2) C(6) N(5) N(6) O(3) O(3) N(6) N(7) O(4) O(4) N(7) N(8) O(5) O(5) N(8) N(9) O(6i O(6) N(9)
2 N(7) N(7) N(8) N(8) N(8) N(9) N(9) N(9) C(1) C(2) C(3) C(4) C(5) C(6) C(7) C(8) C(9) C(lO) C(l1) C(l2) C(l3) C(l4) C(l5) C(l6) C(l7) C(l8) C(l9) C(20) C(21) C(22) c(23) c(24)
Atom 3
Angle (deg)
W3 CW
118.3(5) 109.4(6) 121.4(4) 117.6(5) 111.2(6) 118.9(5) 122.3(6) 112.6(7) 112.8(6) 113.8(7) 108.2(7) 109.8(7) 113.0(8) 108.4(6) 114.5(7) 113.0(7) 110.1(7) 112.8(7) 111.7(7) 109.6(6) 109.6(7) 112.3(7) 110.9(8) 109.7(6) 108.5(6) 111.0(6) 111.1(6) 108.8(6) 112.9(7) 118.0(l) 115.8(8) 115.5(9)
C(l7) C(20) C(20) C(21) c(24) c(24) C(2) C(3) C(2) C(5) C(4) C(7) C(8) C(7) C(lO) C(9) C(l2) C(l1) C(l4) C(l3) C(l6) C(l5) C(l8) C(l7) C(20) C(l9) C(22) C(21) c(24) c(23)
case, with an O(4) atom from an adjacent molecule. Therefore, we may conclude that the dinucleophilic attack of N,P,C& occurs through a twostep procedure and not in a bimolecular concerted way. Another striking feature comes from the uncommonly severe lack of planarity of the N,P, ring in the title molecule. Indeed, the N(1) atom deviates by 0.20 A from the P(l)-N(3)-P(3)-N(2)-P(2) plane towards the N(4) exocyclic nitrogen atom. This situation is due to the noticeable distortion of the loop (Fig. 1) with respect to the cyclophosphazenic ring; seven atoms, N(5), C(8), C(7), C(6), O(2), C(5) and C(4), are below this plane whereas only
363
Fig. 1. A perspective view of the title molecule with numbering of atoms and the N,P, ring perpendicular to the plane of the figure (slightly tilted for clarity).
four atoms, N(4), C(l), C(2) and C(3), are above it (O(1) belongs to the cyclophosphazenic plane). Such a dissymmetry, which makes the lower part of the SPIRO loop more bulky than its upper part, pushes the closest endocyclic nitrogen atom, N(l), outside of the N,P, ring towards the less hindered part of the molecular space. CONCLUSION
The molecular structure of the title compound reveals a surprising “chisteralike” conformation of its SPIRO loop due to strong intra- and intermolecular hydrogen bonds. Such a peculiar conformation makes this loop prone to metal recognition according to the fact that insertion of hard metals (lithium, zinc, magnesium and aluminium) in the inner cavity of SPIRO (30203) leads to SPIRO loops which adopt precisely “chistera-like” conformations. Thus, we may predict that the title molecule will be capable of accepting metals such as calcium, gadolinium, hafnium and europium for further radiopaques design. Moreover, since peramino derivatives of
364
bC14
b
Fig. 2. A perspective view of the title molecule with the N,P, ring parallel to the plane of the figure (slightly tilted for clarity).
Fig. 3. A perspective view of the molecular packing.
365
SPIRO (30203), such as the title compound, are (i) highly soluble in physiological serum and (ii) poorly immunodepressive, we may expect that their metallated cryptates will be suitable for many biological applications. REFERENCES
2 3 4 5 6 7
8 9
10 11 12 13 14 15 16 17
F. Sournies, P. Castera, A. El Bakili and J-F. Labarre, J. Mol. Struct., 221 (1990) 239. F. Sournies, P. Castera, J-P. Faucher, M. Graffeuil and J-F. Labarre, J. Mol. Struct., 221 (1990) 245. A. El Bakili, P. Castera, J-P. Faucher, F. Sournies and J-F. Labarre, J. Mol. Struct., 195 (1989) 21. F. Sournies, A. El Bakili, J-F. Labarre and B. Perly, J. Mol. Struct., 196 (1989) 201. F. Sournies, A. El Bakili, B. Zanin, J-F. Labarre and J. Jaud, J. Mol. Struct., 220 (1990) 43. R. Enjalbert, J. Galy, A. El Bakili, P. Castera, J-P. Faucher, F. Sournies and J-F. Labarre, J. Mol. Struct., 196 (1989) 207. T.S. Cameron, A. Linden, F. Sournies, A. El Bakili and J-F. Labarre, J. Mol. Struct., 197 (1989) 41. T.S. Cameron, A. Linden, A. El Bakili, P. Castera, J-P. Faucher, M. Graffeuil, F. Sournies and J-F. Labarre, J. Mol. Struct., 212 (1989) 281. J. Jaud, F. Sournies and JF. Labarre, J. Mol. Struct., 212 (1989) 305. R. Enjalbert, J. Galy, F. Sournies and J-F. Labarre, J. Mol. Struct., 221 (1990) 53. R. Enjalbert, J. Galy, B. Zanin, J-P. Bonnet, F. Sournies and J-F. Labarre, J. Mol. Struct., 246 (1991) 123. M. Veith, M. Kross and J-F. Labarre, J. Mol. Struct., 243 (1991) 189. M. Veith, M. Kross and J-F. Labarre, J. Mol. Struct., 248 (1991) 345. D.T. Cromer and J.T. Waber, International Tables for X-Ray Crystallography, Vol. IV, Kynoch Press, Birmingham, 1974, Table 2.2 A. D.T. Cromer and D. Liberman, International Tables for X-Ray Crystallography, Vol. IV, Kynoch Press, 1974, Birmingham, Table 2.3.1. G. Sheldrick, Program for Crystal Structure Determination, Version SHELX-86, Oxford University Press, Cambridge, 1986. C.K. Johnson, ORTEP II,Report ORNL-5138, Oak Ridge National Laboratory, TN, 1976.