Dalton Transactions

Solution structure of R₂Sn(IV)--N-acetyl-neuraminate (R = Me, Bu) complexes in D₂O and DMSO-d₆: Experimental NMR and DFT computational study

Nuccio Bertazzi*^a, Girolamo Casella^a, Francesco Ferrante^b, Lorenzo Pellerito^a, Archimede Rotondo^c and Enrico Rotondo^c
aDipartimento di Chimica Inorganica e Analitica Stanislao Cannizzaro, Università di Palermo, Viale delle Scienze Parco d'Orleans II, Ed.17, 90128, Palermo. (Italy). E-mail: bertazzi@unipa.it; Fax: +39 091 427584; Tel: +39 091 6451763
^bDipartimento di Chimica Fisica Filippo Accascina, Università di Palermo, Viale delle Scienze Parco d'Orleans II, Ed. 17, 90128, Palermo, (Italy)
^cDipartimento di Chmica Inorganica, Chimica Analitica e Chimica Fisica, Università di Messina, Salita sperone, 31, 98100, Messina, (Italy)

Two diorganotin(IV)–NANA complexes (NANA (1) = -N-acetyl-Neuraminic Acid = 5-amino-3,5-dideoxy-D-glycero--D-galactononulosic acid) with formula Me₂Sn(IV)NANA (2) and Bu₂Sn(IV)NANA (3) were synthesized and characterized by ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopy, both in D₂O and DMSO-d₆ solutions. The experimental data in DMSO suggested the monosaccharide bidentate chelation via O1 carboxylate and vicinal O2 alkoxide atoms, which, in D₂O, can be dynamically extended to a third binding site (O8 atom) of the pendant chain. Coordination at the tin atom is discussed on the basis of experimental NMR data and DFT calculation.

Neuraminic acid (C₉H₁₇O₈N) is the unsubstituted basic unit common to a natural occurring group of compounds. These residues, often N-acetylated and sometimes O-substituted, are known as sialic acids¹ and are among the most important cell surface carbohydrates.² They are usually located in the non-reducing ends of glycoproteins, glycolipids and polysaccharides,³ on the outer cell membranes of several bacteria, protozoa and tissues of higher animals. There, sialic acids play lead-roles in recognition and immunological processes^4,5 behaving mostly as masks by preventing the recognition of receptors or antigens by the components of the immune-defense system.⁵

NANA (Fig. 1) is the main sialic acid in humans and has attracted growing attention from organic and medicinal chemists prompting the synthesis of a wide number of derivatives.⁶ Since NANA is a relatively strong acid (pK_a = 2.6), it is deprotonated at physiological pH, thereby providing negative charges onto the red blood cell surface.⁷ This accounts for the important role played in the erythrocytes lifetime regulation.⁸ In naturally occurring glycoconjugates, sialic acids are only in the configuration. A unique exception is represented by the CMP-sialic acids form where the anomeric carbon is in the configuration.⁹

	Fig. 1 -N-AcetylNeuraminic Acid (NANA) and numbering of carbon atoms.

Few NMR studies on NANA metal complexes have been so far carried out. Investigation of NANA complexes with alkali and alkaline earth metal ions¹⁰ suggest that the glycerol side chain is involved in the coordination. This complexing ability toward Ca^II was later supported by a careful NMR analysis.¹¹ Further studies on NANA complexes with either biological or toxic metal ions, still suggested, but did not prove pendant chain involvement in coordination.¹²

It has been shown that complexes derived from organotin(IV) species and carbohydrates, or their acidic derivatives, have different biological properties with respect to those of free organometallic and ligand moieties.^13,14

When allowed by geometrical and hindering factors monoacidic derivatives of carbohydrates often act like dianionic chelating agents towards diorganotin(IV), via carboxylate oxygen atoms and suitable alkoxide groups, even at low pH values.^14–18 In this context ¹¹⁹Sn, ¹H and ¹³C NMR spectroscopy represent a powerful tool in order to investigate organotin(IV) species in solution. ¹¹⁹Sn chemical shift (cs) is very sensitive to the coordination environment of the metal center as well as to dynamic processes such as self-association and/or coordinated solvent exchange.^19–22

Theoretical ¹¹⁹Sn cs prediction at the DFT-GIAO level for organotin(IV) complexes proved useful in validating the chemical structure on the basis of the mentioned cs/structure correlation^23–25 even in the presence of dynamic exchange.²⁶

In this work two novel complexes of NANA coordinated with dimethyltin(IV) and dibutyltin(IV) moieties were characterized in D₂O and DMSO-d₆ by using 1D and 2D specific NMR techniques. In order to support the structural characterizations, NMR data are compared with calculated ¹¹⁹Sn and ¹³C cs at the DFT-GIAO level, taking into account also a possible solvent coordination to the metal center.

¹H and ¹³C resonances and ^2,3J(¹H,¹H) scalar coupling constants for (1), (2) and (3) are reported in Tables 1, 2 and 3, respectively.

	H3eq	H3ax	H4	H5	H6	H7	H8	H9	H9	H11	Ha	Ha	Ha	Ha/Mea
D2O
NANA (1) pH = 3	1.79	2.20	4.01	3.87	3.96	3.48	3.71	3.57	3.79	2.01	—	—	—	—
Me2SnNANA (2) pH = 3.5	2.08	2.08	4.09	3.91	4.04	3.53	3.69	3.64	3.81	2.05	—	—	—	0.85
	0.29	–0.12	0.08	0.04	0.08	0.05	–0.02	0.07	0.02	0.04
Bu2SnNANA (3) pH = 2.5	2.02	2.07	4.06	3.90	4.02	3.51	3.68	3.63	3.89	2.07	1.54	1.58	1.32	0.86
	0.23	–0.13	0.05	0.03	0.06	0.03	–0.03	0.06	0.10	0.06
DMSO-d6
NANA (1)	1.67	1.97	3.83	3.48	3.73	3.15	3.48	3.29	3.59	1.86	—	—	—	—
Me2SnNANA (2)	2.03	1.67	3.87	3.57	3.82	3.23	3.42	3.33	3.45	1.88	—	—	—	0.56
	0.36	–0.30	0.04	0.09	0.09	0.08	–0.06	0.04	–0.14	0.02
Bu2SnNANA (3)	2.05	1.67	3.88	3.47	3.83	3.25	3.39	3.36	3.54	1.90	1.50	1.28	1.26	0.84
	0.38	–0.30	0.05	–0.01	0.10	0.10	–0.09	0.07	–0.05	0.04
a H, H, H, H = butylic protons of Bu2Sn(IV)2+; Me = methylic protons of Me2Sn(IV)2+.

	C1	C2	C3	C4	C5	C6	C7	C8	C9	C10	C11	Ca	Ca	Ca	Ca/Mea
D2O
NANA (1) pH = 3.0	178.1	98.7	41.8	69.7	54.8	72.9	71.1	72.9	65.9	177.5	24.8	—	—	—	—
Me2SnNANA (2) pH = 3.5	180.9	99.7	42.8	70.1	55.2	72.7	71.1	72.9	65.8	177.5	24.8	—	—	—	7.1
	2.8	1.0	1.0	0.4	0.4	–0.2	0.0	0.0	–0.1	0.0	0.0
Bu2SnNANA (3) pH = 2.5	181.0	99.7	42.9	70.1	55.3	72.7	71.2	73.1	65.7	177.6	24.8	26.5	28.9	28.6	15.5
	2.9	1.0	1.1	0.4	0.5	–0.2	0.1	0.2	–0.2	0.1	0.0
DMSO-d6
NANA (1)	171.4	94.7	42.2	65.7	53.0	70.3	69.1	69.8	63.6	171.9	22.6	—	—	—	—
Me2SnNANA (2)	175.1	96.7	42.2	66.9	54.1	70.6	69.5	70.1	63.9	172.0	22.8	—	—	—	3.5
	3.7	2.0	0.0	1.2	1.1	0.3	0.4	0.3	0.3	0.1	0.2
Bu2SnNANA (3)	174.9	96.5	42.2	66.7	54.1	70.6	69.3	69.9	63.5	171.8	22.7	26.6	25.9	21.8	13.6
	3.5	1.8	0.0	1.0	1.1	0.3	0.2	0.1	–0.1	–0.1	0.1
a C, C, C, C = butylic carbons of Bu2Sn(IV)2+; Me = methylic carbons of Me2Sn(IV)2+.

	2J3a,3e	3J3a,4	3J3e,4	3J4,5	3J5,6	3J6,7	3J7,8	3J8,9	3J8,9	3J9,9
(1)	12.9	11.2	4.8	10.2	10.1	0.7	9.2	6.2	2.5	11.7
		(174°)	(56°)	(176°)	(172°)
(2)	—	—	—	10.2	10.2
				(176°a)	(172°a)	0.7	9.0	5.7	2.3	11.3
(3)	—	—	—	10.5	10.3
				(176°a)	(172°a)	n.d	8.7	7.6	—	11.2
a Largest dihedral angles obtained for 3J4,5 = 3J5,6 = 9.3 Hz.

For (1) data are similar to those previously reported.^10–123J(H_n, H_m; nm) coupling constants in (1), (2) and (3) are consistent with the typical ²C₅ rigid conformation of the monosaccharidic ring, where, in the glycerol chain, the H8 is trans to H7 (Fig. 1). The ¹³C{¹H} spectra show that C1, C2 and C3 in compounds (2) and (3) have a larger than the free NANA (1), which is consistent with coordination of both carboxylate O1 and the alkoxide O2 atoms (Fig. 2).

	Fig. 2 Coordination of NANA via carboxylic and alkoxydic O2 oxygen atoms (R = Me, Bu).

Complexation does not cause important changes in NANA proton resonances, except for H3eq and H3ax which are well separated in the free ligand, but gives rise to overlapped signals in (2) and (3) (see also NMR study in DMSO-_d6 section). The 2D-NOESY spectra (Fig. 3), besides the expected through-space intraligand contacts, also show a dipolar interaction between H8 and Sn-bonded alkyl protons (methyl in (2) and -CH₂ protons in (3), respectively).

	Fig. 3 1H 2D-NOESY spectrum of (2). The CH3–H8 signal is indicated.

This strongly supports that also O8 acts, at least temporary, as third coordinating site (Fig. 4). Fast reversible, probably proton promoted, cleavage of Sn–O bonds is confirmed by the lack of NANA-proton/¹¹⁹Sn scalar coupling.

	Fig. 4 Coordination of NANA via carboxylic and alkoxydic O8 oxygen atoms (R = Me, Bu).

Methyl protons of the R₂Sn(IV) moiety in compound (2) are observed as a singlet at 0.85 ppm flanked by Sn satellites [²J(¹¹⁹Sn, ¹H) = 87 Hz]. This value is consistent with a Me–Sn–Me angle close to 140°.²⁸ From the acid pD value we infer that also hydrolyzed species should occur in solution and they have ¹³C cs values close to the non-hydrolyzed ones (See Computational Study in D₂O section).

Due to the fast ligand exchange, ¹¹⁹Sn{¹H} spectrum of (2) shows a very broad signal centered at –165 ppm (with a line width W_1/2 800 Hz). The cs value, which is borderline for a penta- or hexa-coordinated tin(IV),^15,18 would suggest the presence of at least one solvent molecule in the tin coordination sphere. For (3) broad signals and poor solubility prevented any ¹¹⁹Sn resonance detection.

¹³C{¹H} spectra are similar to those obtained in water, with a systematic shift towards lower frequencies. Again, the major are recorded for C1 and C2 accounting for the carboxylate O1 and the next O2 bidentate coordination (Table 2). Methyl-¹¹⁹Sn scalar couplings of (2) [¹J(¹¹⁹Sn, ¹³C) = 675 Hz and ²J(¹¹⁹Sn, ¹H) = 83 Hz] suit a C–Sn–C angle of ca. 135°.^28,291H NMR data show that the metal exerts opposite effects on H3ax and H3eq frequencies, driven by the coordination geometry to lay in different d-electrons anisotropic shielding cones (Table 1). On this basis, H3 are proportional to the time spent by O2 as coordinating site. In water, fast reversible Sn–O2 cleavage, causes H3ax and H3eq intermediate opposite shift leading to signal collapse. In DMSO-_d6 the enhanced stability of Sn–O2 bond fits the observed frequency inversion. Lower exchange rates of (2) and (3) in the aprotic DMSO-_d6 solvent are witnessed by sharper ¹¹⁹Sn signals at (–126 ppm, W_1/2 = 51 Hz, and –148 ppm, W_1/2 =22 Hz respectively). Moreover, long-range scalar coupling connections of H3ax and H3eq with ¹¹⁹ Sn for (2) and (3), present only in DMSO_d6 prove Sn–O2 bond kinetic stability (Fig. 2). The lack of any other scalar coupling with NANA protons supports that coordination involves exclusively O1 and O2 atoms. Unlike the D₂O case, 2D-NOESY did not detect through-space connection between Sn–alkyl and NANA pendant chain protons, according with the lack of O8–Sn interaction.

The computational study was performed considering three relevant issues, namely: the alternate O2/O8 alkoxide coordination (besides the carboxylic oxygen), the interaction between tin and water molecules, by explicitly including solvent molecules in the metal first coordination sphere and, finally, the previously mentioned occurrence of hydrolysed species. In this way a total of sixteen different model structures have been set up (Fig. 5 shows the models labeling). Tetra-coordinated tin structures were not considered because of the large estimated C–Sn–C angle. Selected calculated structural data for all the optimized structures are reported as Electronic Supplementary Information (ESI).

	Fig. 5 Labeling of the models: (a) Coordination of NANA viaO1 and O2 with one water molecule in the tin coordination sphere for compound (2) (model A1). The A2 model for (2) considers the presence of two water molecules. For compound (3) the corresponding models are labeled C1 and C2. (b) Coordination of NANA viaO1 and O8 with one water molecule in the tin coordination sphere for compound (2) (model B1). The B2 model for (2) considers the presence of two water molecules. For compound (3) the corresponding models are labeled D1 and D2; (c) Coordination of NANA viaO1 and O2 with one OH ligand bound to tin for compound (2) (model HA1). The HA2 model for (2) considers one water molecule in addition to the OH group. For compound (3) the corresponding models are labeled HC1 and HC2. (d) Coordination of NANA viaO1 and O8 with one OH ligand bound to tin for compound (2) (model HB1). The HB2 model for (2) considers one water molecule in addition to the OH group. For compound (3) the corresponding models are labeled HD1 and HD2.

Sn–C and Sn–O bond distances, including coordinated water molecules, are all in the ranges experimentally observed.³⁰ For the models with one and two coordinated waters, the calculated C–Sn–C angles fall into two distinct ranges namely, 125°–132° and 132°–145°, respectively. For compound (2) the corresponding value estimated from the experimental ²J(¹¹⁹Sn, ¹H) is in agreement with models having two water molecules bonded to the metal center. For compound (3) the models show a similar trend for the C–Sn–C angle of the butyl chains but the lack of an experimental ²J(¹¹⁹Sn, ¹H) does not allow an independent estimation of its value. The lowest calculated distances between the alkyl groups [CH₃ in (2), -CH₂ in (3)] and H8 for the B1, B2, D1, D2 models are in the 200–250 ppm range justifying the observed NOESY signal attributed to the ligand chelation through carboxylate and O8 alcoxide group. Finally, calculated dihedral angles are in agreement with the ones given in Table 3, confirming the ²C₅ conformation of the pyranosidic ring. The calculated ¹¹⁹Sn cs for compound (2) (Table 4) obtained for the A2 and the B2 models indicate that the tin centers, in both models, experience a similar electronic structure and are close to the experimental one, on the contrary, ¹¹⁹Sn cs values for the A1 and B1 models indicate a different electronic distribution at the tin atom and are sensibly different from the experimental one. Thus the models with two water molecules well match the experimental ¹¹⁹Sn cs and the tin is formally hexa-coordinated. While the experimental ¹¹⁹Sn cs value (–165 ppm) for compound (2) has been so far considered typical for a penta-coordinated dialkyltin(IV)^18,21,22 such a discrepancy could be due to the weakness of the tin–solvent bond. For compound (3), in the absence of an experimental ¹¹⁹Sn cs value, calculated data for the ¹¹⁹Sn cs (see ESI) did not allow any suitable assignment of the studied models, we merely observe that these ones appear acceptable.

The ¹³C cs for all models, reported in Table 4 for (1) and (2) and as ESI for (3), are fairly close to the experimental values and confirm that coordination does not sensibly affect the ¹³C frequencies measured for the ligand.

Calculated Sn–C and Sn–O distances for the hydrolyzed models also fall in the expected experimental ranges.³⁰ The presence of the OH^– ligand in the tin first coordination sphere causes the weakening of the tin–carboxylate Sn–O1 bond distances (see ESI) with the exception of the HC1 and the HC2 models. Optimization of HA2, HB2 and HC2 models gave structures where the water molecule lies well outside a coordination bond distance and the tin is penta-coordinated. Taking into account the solution pD value (Table 1) we infer that the amount of hydrolyzed fraction of (2) is less than of 1% of the analytical concentration (ca. 4.3 × 10^–2 mol L^–1) which is outside the instrumental sensitivity limit. In this respect, calculated ¹³C and ¹¹⁹Sn cs values for compound (2) (Table 4) cannot be compared with experimental values, and we note that ¹¹⁹Sn cs fall to frequencies lower than those calculated for non-hydrolyzed models, which can be regarded to be the strongly bonded OH^– group. For compound (3) the solution pD value (Table 1) indicates that hydrolysis proceeds to an extent of ca. 30%. The calculated ¹¹⁹Sn cs for the HC2 model is similar to the values obtained for HC1 and HD1 confirming the view of a penta-coordinated tin in this model (see ESI). Also in this case the calculated ¹¹⁹Sn cs resulted in more shielding with respect to the same penta-coordinated tin in the non-hydrolyzed models. In HD2 tin is hexa-coordinated with a strongly bonded water molecule . This justifies the large C–Sn–C angle and the increased shielding denounced by the calculated ¹¹⁹Sn cs. Again, the lack of an experimental ¹¹⁹Sn cs value for (3) does not allow comparison with the calculated ones. For compounds (2) and (3) the calculated ¹³C cs for hydrolyzed and non-hydrolyzed models are very similar (with few exceptions) justifying the occurrence of single signals in the spectrum. Some discrepancies are probably dependent on differences in the conformational arrangement such as, for example, the C6 cs value of HA2, which has a much larger Oe–C3–C4–C6 dihedral angle.

NANA (1), dimethyltin(IV) oxide (DMTO) and dibutyltin(IV) oxide (DBTO) were Fluka products (Buchs, Switzerland) used without further purification.

NANA and DMTO, suspended in 50 mL of H₂O, in the 1 : 1 stoichiometric ratio (1 mmol : 1 mmol), were allowed to react for 24 h at about 40 °C, under a constant stirring. The white solid Me₂Sn(IV)NANA complex (2), precipitated on cooling after removal of excess solvent in a rotovapor, has been recovered, recrystallized from cold ethanol (95%) and dried over P₄O₁₀, in a vacuum.

The recrystallized solid has been analyzed for C, H contents, in our laboratory, by using a Vario EL III CHNS elemental analyzer (Elementar Analysensysteme GmbH, Hanau, Germany). Tin content has been analyzed gravimetrically as SnO₂ by treating the compound with a HNO₃/H₂SO₄ mixture according to ref. 31 (Found: C, 33.96; H, 4.92; Sn 27.32. C₁₃H₂₃O₉NSn requires: C, 34.24; H, 5.09; Sn, 26.03%).

Bu₂Sn(IV)NANA (3) has been synthesized with the analogous method for (2) in 1 : 1 H₂O–ethanol mixture, and recrystallized from cold ethanol. C₁₉H₃₅O₉NSn, (Found: C, 41.57; H, 6.38; Sn, 20.19. C₁₉H₃₅O₉NSn requires: C, 42.24; H, 6.54; Sn, 21.98%).

Discrepancies in the tin content are probably due to the behavior of these classes of carbohydrate derivatives which may give final products other than SnO₂ after the thermal decomposition. In particular, according to a previous report,³² the thermal decomposition of organotin(IV) carbohydrate derivatives may give mixtures of SnO₂, SnO, Sn and C as final products. An attempt to synthesize in situ the compound (2) into the NMR tube, gave the same NMR spectra obtained from the isolated solid sample.

All NMR spectra (1D ¹H, ¹³C{¹H} and ¹¹⁹Sn{¹H}; 2D ¹H–¹H COSY and NOESY, ¹H–¹³C HMQC and HMBC, ¹H-¹¹⁹Sn HMBC) were recorded on a Bruker ARX-300 spectrometer at 300.13, 75.47 and 118.90 MHz, with spectral bandwidths of 8, 200 and 400 ppm for proton, carbon and tin, respectively. The spectra for all the samples were run at 298 K in D₂O or DMSO-d₆. D₂O solutions were prepared by dissolving 11.3 mg of (1), 9.2 mg of (2) and 2.6 mg of (3) in 500 µL. Measured pD were 3.0, 3.5 and 2.5, respectively. Low solubility of (3) in D₂O prevented ¹¹⁹Sn spectral resonance detection. Analogous NMR analysis was carried out in DMSO-d₆ by dissolving 14.7, 13.6, 16 mg of (1), (2) and (3), respectively, in 500 µL of solvent. External reference for ¹H and ¹³C were the resonances of 4,4-dimethyl 4-silapentane sodium sulfonate (DSS), while ¹¹⁹Sn spectra was referred to the tetramethyl-tin ¹¹⁹Sn resonance.

The DFT method with the three-parameters hybrid functional B3LYP^33,34 was used for both geometry optimization and calculation of the NMR parameters. Geometry optimization for models referred to the tin complexes (see Computational Study section) as well as for tetramethyltin (TMSn) and 4,4-dimethyl 4-silapentane sodium sulfonate (DSS) (whose ¹¹⁹Sn and the methyl ¹³C cs were calculated as reference), was performed by employing the 6-31G(d,p) basis set for the C, H, N, O atoms and the all-electron Double Zeta Valence plus Polarization (DZVP) basis set for the Sn atom³⁵ (contraction scheme: (18s14p9d)/[6s5p3d]). The calculation of the shielding constants () were performed on the optimized geometries in conjunction with the Gauge Independent Atomic Orbital (GIAO) formalism by using the Included Gauge Localized Orbital-II (IGLO-II) basis set for the tin atom³⁶ (contraction scheme: (17s13p11d)/[12s11p9d]) and the 6-31G(d,p) basis set for the C, H, N, O atoms. An integration grid of 99 radial shells and 302 angular points was used.

¹¹⁹Sn and ¹³C cs were obtained by difference between the calculated shielding constants for the complexes and the corresponding value for the relative reference compounds according to = (_ref. –). All calculations were performed by using the Gaussian 03 package.³⁷

Experimental data show interesting differences in NANA coordination towards the diorganotin(IV) moieties in D₂O and in DMSO-d₆. In D₂O, data state, beyond the carboxylate oxygen atom O1, the dynamic participation to the coordination from both O2 and O8 hydroxyl oxygen atoms. Fast proton catalyzed ligand exchange is supported by the washing of scalar coupling between ¹¹⁹Sn and NANA ¹H/¹³C nuclei. On the other hand Sn-alkyl scalar coupling validate solvent coordination leading to penta- and/or hexa-coordinated species.

The lack of proton catalysis in DMSO-d₆ freezes ligand exchange so that scalar coupling between ¹¹⁹Sn and NANA ¹H/¹³C nuclei are observed as confirmed by the coupling of H3 protons with the tin atom. Data support O1 and O2 NANA chelation and also in this case, the C–Sn–C angle suggest a solvent participation to the coordination leading to a penta- or hexa-coordinated tin.

DFT calculations have proved effective in matching the proposed structures in solution and comparison of calculated and experimental cs allowed the assignment of the exchanging species highlighting also the effect of the solvent. The calculation gave ¹³C cs which are in sensible agreement with the experimental values. However, since there are not very appreciable differences for the single C atom frequencies for free and coordinated ligands this parameter does not allow a choice among the different proposed models. On the contrary, the calculated ¹¹⁹Sn cs have been useful in the aforementioned choice. For the compound (2), by comparison of the experimental and calculated ¹¹⁹Sn cs, the A2 and B2 models proposed for the non-hydrolyzed structures showed the better agreement between experimental and calculated data. In these models the tin atom is formally hexa-coordinated due to the occurrence of two water molecules in its first coordination sphere confirming the participation of the solvent upon the tin coordination. For the same compound the HA1, HA2 and HB2 models proposed for the hydrolyzed species all seem acceptable even if the small amount of hydrolyzed species could not be detected in the NMR spectra. For compound (3), the lack of the experimental ¹¹⁹Sn cs in D₂O did not allow any suitable assignment of the models to the proposed experimental structures.

Acknowledgements

Financial support by the Ministero dell'Istruzione, dell'Università e della Ricerca (M.I.U.R., CIP 2004059078_003), Roma, by the Università di Palermo (ORPA 041443) and by the Università di Messina is gratefully acknowledged. The electronic structure calculations were performed using the UK National Computational Software Service (EPSRC).

References

1		F. G. Blix, A. Gottschalk and E. Klenk, Nature, 1957, 179, 1088 [Links].
2		G. M. W. Cook and R. W. Stoddart, in Surface Carbohydrates of the Eukaryotic Cell, Academic Press, New York, 1973, pp. 56–97.
3		H. Wiegandt, in New Comprehensive Biochemistry: Glycolipids, ed. A. Neuberger and L. L. M. van Deenen, Elsevier, New York, 1985, vol. 10, pp. 28–36.
4		D. A. Cheresh, M. D. Pierschbacker, M. A. Herzig and K. J. Mujoo, J. Cell Biol., 1986, 102, 688–696 [Links].
5		G. R. Moe, S. Tan and D. M. Granoff, FEMS Immunol. Med. Microbiol., 1999, 26, 209–226 [Links] and references therein.
6		M. J. Kiefel and M. von Itzstein, Chem. Rev., 2002, 102, 471–490 [Links].
7		E. H. Eylar, M. A. Mandof, O. V. Brody and J. L. Oncley, J. Biol. Chem., 1962, 237, 1992–2000 [Links].
8		R. Schauer, A. K. Shukla, C. Schröeder and E. Muller, Pure Appl. Chem., 1984, 56, 907 [Links].
9		T. Angata and A. Varki, Chem. Rev., 2002, 102, 439–469 [Links].
10		J. P. Behr and J. M. Lehn, FEBS Lett., 1972, 22, 178–180 [Links].
11		L. W. Jaques, E. L. Brown, J. M. Barrett, W. S. Brey, Jr. and W. Weltner, Jr., J. Biol. Chem., 1977, 252, 4533–4538 [Links].
12		M. Saladini, L. Menabue and E. Ferrari, J. Inorg. Biochem., 2002, 88, 61–68 [Links].
13		R. Barbieri, L. Pellerito, G. Ruisi and M. T. Lo Giudice, Inorg. Chim. Acta, 1982, 6, 39–40.
14		N. Bertazzi, G. Casella, P. D'Agati, T. Fiore, C. Mansueto, V. Mansueto, L. Nagy, C. Pellerito, L. Pellerito, I. D. Sciacca and M. Scopelliti, presented in part at the 4th Symposium on Pharmaco-Bio-Metallics, Lecce (IT), October, 2004.
15		B. Gyurcsik and L. Nagy, Coord. Chem. Rev., 2000, 203, 81–149 [Links].
16		N. Bertazzi, G. Bruschetta, G. Casella, L. Pellerito, E. Rotondo and M. Scopelliti, Appl. Organomet. Chem., 2003, 17, 932–939 [Links].
17		N. Buzás, L. Nagy, E. Kuzmann, A. Vértes and K. Burger, Inorg. Chim. Acta, 1998, 274, 167–176 [Links].
18		T. B. Grindley, Adv. Carbohydr. Chem. Biochem., 1998, 53, 17–142 [Links].
19		P. J. Smith and A. P. Tupiauskas, Annu. Rep. NMR Spectrosc., 1978, 8, 291–370 [Links].
20		R. Hani and R. A. Geanagel, Coord. Chem. Rev., 1982, 44, 229–246 [Links].
21		B. Wrackmeyer, Annu. Rep. NMR Spectrosc., 1985, 16, 73–186 [Links].
22		B. Wrackmeyer, Annu. Rep. NMR Spectrosc., 1999, 38, 203–264 [Links].
23		R. Vivas-Reyes, F. De Proft, M. Biesemans, R. Willem and P. Geerlings, J. Phys. Chem. A, 2002, 106, 2753–2759 [Links].
24		P. Avalle, R. K. Harris and R. D. Fischer, Phys. Chem. Chem. Phys., 2002, 4, 3558–3561 [Links]; P. Avalle, R. K. Harris, P. B. Kardakov and P. J. Wilson, Phys. Chem. Chem. Phys., 2002, 4, 5925–5932 [Links].
25		A. Bagno, G. Casella and G. Saielli, J. Chem. Theor. Comput., 2006, 2, 37–46 [Links].
26		A. Bagno, N. Bertazzi, G. Casella, L. Pellerito, G. Saielli and I. D. Sciacca, J. Phys. Org. Chem., 2006, 19, 874–883 [Links].
27		C. A. G. Haasnoot, F. A. A. M. dew Leeuw and C. Altona, Tetrahedron, 1980, 36, 2783–2792 [Links].
28		T. P. Lockhart and W. F. Manders, Inorg. Chem., 1986, 25, 892–895 [Links].
29		T. P. Lockhart, W. F. Manders and J. J. Zuckerman, J. Am. Chem. Soc., 1985, 107, 4547–4548 [Links].
30		J. A. Zubieta and J. J. Zuckerman, Prog. Inorg. Chem., 1978, 24, 251–475 [Links].
31		W. P. Neumann, in The Organic Chemistry of Tin, ed. D. Seyferth, Interscience Publishers, London, 1970, pp. 211–212.
32		J. D. Donaldson, S. G. Grimes, L. Pellerito, M. A. Girasolo, P. J. Smith, A. Cambria and M. Famà, Polyhedron, 1987, 6, 383–386 [Links].
33		A. D. Becke, J. Chem. Phys., 1993, 98, 5648–5652 [Links].
34		C. Lee, W. Yang and R. G. Parr, Phys. Rev. B, 1988, 37, 785–789 [Links].
35		N. Godbout, D. R. Salahub, J. Andzelm and E. Wimmer, Can. J. Chem., 1992, 70, 560–571 [Links].
36		W. Kutzelnigg, U. Fleischer and M. Schindler, in NMR Basic Principles and Progress, Springer, Heidelberg, 1990, pp. 165–262.
37		Gaussian 03, Revision C.01, Gaussian, Inc., Wallingford CT, 2004, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji,M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala,K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez and J. A. Pople.

Footnote

Electronic supplementary information (ESI) available: Relevant distances (pm) and angles (°) obtained for the optimized models; Calculated 119Sn and 13C NMR cs (ppm) for non-hydrolyzed and hydrolyzed Bu2SnNANA (3). See DOI: 10.1039/b616330k