Bloqueo de los probables receptores para el virus de Zika en la línea celular

Attempts to extend the synthesis of the wide range of bis chelated derivatives with the second generation poly(pyrazolyl)borate [HB(3,5-Me2Pz)3]', have proved to be unsuccessful. Although this has been the case mainly due to rapid decomposition of the ligand, rather surprisingly it is possible to adapt this synthesis to the neutral tridentate ligands, HC(Pz)3 and HC(3,5-Me2Pz)3. Treatment o f the complex [ {Ru(ri^-C6HJCI2}2],

pre-stirred in MeCN for 30 minutes, with HC(Pz)3 or HC(3,5-Me2Pz)3 followed by work

up with methanolic NH4[PFJ results in the isolation of yellow powders formulated as

[Ru(p^-C,H,){k^-HC(Pz)3)C1][PF,] [16] and [Ru(p'-C,HJ{K'-HC(3,5-Me2Pz)3}Cl][PFJ [17] (Figure 2.15).

+ Ru

R

Figure 2.15 Ruthenium(II)(ri^-QH6){K^-HC(3,5-R2Pz)3} complexes, (R = H [16] and Me [17]).

R u(II)(arene)poly(pyrazolyl)borates and methanes

The ‘H NMR spectrum o f [17] consists of eight singlets. Whilst four of the low field signals, ô 8.35, 6.46, 6.17 and 5.78 ppm, arise fi-om the acidic proton H'*(Pz‘),

(Pz^) and the n bonded benzene respectively, the remaining signals in the aliphatic region of the spectrum, Ô 2.70, 2.69, 2.15 and 1.73 ppm, are due to the presence of two distinct pairs of methyl groups, Me^ (Pz‘), Me^ (Pz^), Me^ (Pz') and Me^ (Pz^).

As has been pointed out previously the appearance o f two sets o f signals with 1:2 integral ratio is consistent with the formulation o f [17] as a bis chelated derivative. It is notable that the signals for the unique pyrazolyl group appear at higher fields, consistent with what is expected for an uncoordinated pyrazolyl substituent. A similar pattern is also found in the ‘^C NMR spectrum (unique Pz: 150.65 C \ 13.49 Me^, 142.52 10.54 Me^ and 110.87 C*; doubly degenerate signals: 159.53 C^, 16.70 M e\ 148.38 11.75 Me" and 111.52 C ).

The X-ray structure of the cation in [17] is shown in Figure 2.16. Tables of atomic coordinates, bond lengths and angles can be found in the experimental section. Inspection of the structure o f [17] reveals the molecule to exist as a half-sandwich complex with, if one assumes the arene occupies three facial sites, a distorted octahedral geometry at the ruthenium centre. The ruthenium atom is Ti-bonded to the arene ligand with an average Ru-C distance of 2.204(7) Â, and a separation between the arene plane and the ruthenium atom of 1.71 Â. These values are characteristically similar to those

Ru(JI)(arene)poly(pyrazolyl)borates and methanes

observed for [15], 2.197(7) for Ru-C and 1.68 Â for Ru-ring centroid, as well as other related ‘ruthenium(II)(T]^-arene)’ complexes.

The Ru-Cl bond distance in [17], 2.415(2) A, is significantly longer than that found in [15] 2.397(2) A. In addition to being bonded to the arene and the chloride ligand the ruthenium atom is also directly coordinated to two endocycXic nitrogen atoms (N22 and N32) of the pyrazolyl groups, with an average distance of 2.145(4) A. It is notable that all three metal-ligand distances are longer for [17] than for [15], most likely as a consequence o f the lack of electrostatic attraction between the two components of the structure. These metal-nitrogen distances are longer than those in related tris chelated complexes, such as [2] 2.113(4) A and [Ru(r|^-Cp){K^-HB(Pz)3}], 2.128(3) A,®^ it is

comparable with a [HB(3,5-Me2Pz)3]‘ based compound, [Ru(K^-(p-H)B(3,5- Me2Pz)3}Me(r|'^-COD)]’“ 2.158(3) A. The bite angle of the chelating ligands of 84.9(2)°

in [17] is not significantly different from those found in any of the other compounds discussed in this chapter. Although the overall geometry at the boron atom in [15] is essentially tetrahedral (average N-B-N value of 108.8 °) the geometry about the corresponding carbon atom in [17] is more distorted, 111.5 °.

Ru(II)((ircn e)p o lv(p \ro zo lyl)b o ra ies and m ethanes C4 C3 ■ I A<\vX \ ''11 c l\31 I

R u(IJ)(arene)poly(pyrazolyI)borates and methanes

The most notable difference between the molecular structures of [15] and [17] is the relative positions of the uncoordinated pyrazolyl groups. Examination o f Figures 2.14 and 2.16 reveals that while in [15] the uncoordinated Teg’ of the tripodal ligand is placed far from the ‘rutbenium(arene)’ fragment the corresponding substituent in [17] is in a relatively closer proximity. Indeed hydrogen atoms on the benzene make short contacts o f 2.65 and 2.70 Â with atoms N(12) and C(15) of the uncomplexed pyrazolyl ring. Conceivably these interactions could result in a stabilisation of the complex, since in order to achieve this orientation the pyrazolyl group must rotate about the Ccentrai'N bond destroying the Q symmetry of the free ligand. It is notable that in [15] the hydridorm(pyrazolyl)borate ligand has retained its approximate Q symmetry. However, in the absence of other evidence it is equally likely that the orientation is a consequence of subtle crystal packing effects.

The synthetic method described above can be extended to compounds in which both the arene and the tripodal ligand carry bulky substituents, e.g. [Ru(T|^-l ,4-Me2CgH4) HC(3,5-Me2Pz)]}Cl][PFJ [18]. The ’H and '^C NMR spectra of [18] are consistent with

the complex being a half sandwich bis chelated derivative. It is however interesting to note that although most o f the previously discussed bis chelated complexes exhibit ‘^C NMR spectra in which the signals of the unique pyrazolyl groups appear at higher fields with respect to the doubly degenerate signals, in the ‘^C NMR spectrum o f the sterically congested [18], this pattern is reversed (unique pyrazolyl signals: 151.51 C^, 13.45 M e\ 142.24 C^ 10.05 Me^ and 110.92 C'*; doubly degenerate pyrazolyl signals: 158.83 C \ 16.75 Me', 146.43 C , 11.83 Me' and 73.86 C").

Ru(II)(arene)poly(pyrazolyl)borates and methanes

It is surprising to find that the bis chelated derivatives of the neutral carbon centred tripodal ligands can be readily isolated in such moderate yields (39 % for [18]) considering the difficulties encountered when trying to synthesise hydrido/ri5(3,5- dimethylpyrazolyl)borate derivatives {e.%. 22 % reported for [Ru(r|^-QH6){K^-HB(3,5- Me2Pz)3}][PFJ [8]) even under mild conditions. The successful isolation o f [18] without

the need to carry out the reaction in a non-polar solvent media {i.e. CHjClj as opposed to MeCN), strongly bears witness to the robustness o f the carbon centred ligand.