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COVER ARTICLEFalvello et al.Using the crystal to engineer the molecule: cis-trans-isomer selection in anionic bis(orotate) complexes

COMMUNICATIONBraga et al.Solvent effect in a “solvent free” reaction

Volume 9 | Number 10 | October 2007 | Pages 835–960

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Using the crystal to engineer the molecule: cis-trans-isomer selection inanionic bis(orotate) complexes

Larry R. Falvello,*a Daniel Ferrer,a Marıa Piedrafita,a Tatiana Solerb and Milagros Tomas*a

Received 18th June 2007, Accepted 12th July 2007

First published as an Advance Article on the web 2nd August 2007

DOI: 10.1039/b709168k

Two chelating orotate22 ligands have been coordinated to the

same metal ion, producing the first dianionic bis-orotate

complex, [Ni(orotate)2(H2O)2]22, whose geometric isomer can

be selected by enabling or vitiating the formation of non-

covalent interactions in the solid in which the product is

isolated. This provides an important example of the influence

and potential use of non-covalent interactions for isomer

selection in the synthesis of coordination compounds, as well as

the manner in which such stereochemical selection can be

achieved by the appropriate use of counterions.

In contrast to the large body of work that has been dedicated to

the use of non-covalent interactions in preparing molecular crystals

with particular packing patterns,1 a much lesser amount of effort

has been directed at the challenging problem of using non-covalent

interaction-forming capability to direct the obtention of molecules

with particular shapes or coordination modes. While the field of

crystal engineering2 has experienced rapid growth—its goal being

the design of solid materials with specific properties based on

the supramolecular structures formed by molecules with given

topologies—the separate goal of isolating molecules with specific

or variable shapes by enabling non-covalent interactions in the

crystals in which those molecules are isolated, has received

relatively little attention.3,4

We report herein the isolation of two stereoisomers of the

first dianionic bis-orotate transition metal complex to have been

structurally characterized, cis- and trans-[Ni(HOr)2(H2O)2]22

(HOr = doubly deprotonated orotic acid). The crystal and

molecular structures demonstrate that the stereochemistry of the

isolated entity depends on the number of external non-covalent

interactions enabled during the synthesis and crystallization.

Coordination complexes that are trapped within a crystalline

environment dominated by non-covalent but directional forces—

hydrogen bonds, other electrostatic interactions, p–p interac-

tions—must sometimes adapt to those surroundings or to changes

produced in them by variation of temperature or pressure.5 At the

same time, the molecule is an active participant in the formation of

its crystalline environment; so unlike the better-known efforts at

crystal engineering, in which a molecule is designed in such a way

as to give a particular packing pattern, in our efforts to influence

molecular shape neither the target molecule nor the extended

crystal environment is known at the outset. Nevertheless, results

obtained to date demonstrate that much useful information is to

be had through systematic experimentation, and that unprece-

dented products are attainable as often as not. As an example,

we have isolated crystals of [Zn(k-N1-uracilate)(k-N3-uracilate)-

(NH3)2],6 a simple tetrahedral complex in which two different

tautomers of uracilate are simultaneously bound to the metal. This

result is demonstrably based on the hydrogen-bonding patterns

formed by the two tautomers. In crystals of trans-[Ni(k-N-cyan)2-

(NH3)4] (cyan = cyanurate, C3H2N3O32), a simple six-coordinate

complex, the molecule undergoes significant, reversible shape

changes as its single-component crystal suffers a second-order

phase transformation.7 In [Pt(CN)3(m-CN)Cu(NH3)4], immersion

of the molecular core in a hydrogen-bonded web forces a severe

bend in the CMN–Cu bond angle [120.1(6)u].8

Orotic acid, C5H4N2O4 (6-uracilcarboxylic acid, H3Or, vitamin

B13), Fig. 1, can be deprotonated, producing H2Or2 (pK1 = 2.09)

and HOr22 (pK2 = 9.28). Orotic acid and some of its derivatives

are involved in biological processes and have applications in

medicinal chemistry.9 The ligands H2Or2 and HOr22 are also

useful as ligands in coordination chemistry and molecular

materials science. Their utility as versatile polyfunctional ligands

derives from the relatively large fraction of their topologies

available for use in structure direction. Of the eleven non-hydrogen

atoms present, more than half (2 N and 4 O) can be employed in

coordination or in the formation of hydrogen bonds or other

electrostatic contacts. Orotates can coordinate to one, two, or three

transition metals at the same time,10 producing mononuclear,

dinuclear or polymeric compounds with a variety of coordination

types.11 The formation of a five-membered chelate is the most

common coordination behavior for HOr22, but no reports have

appeared to date of the isolation and structural characterization of

mononuclear bis-chelate complexes. The only two compounds

reported so far with two five-membered chelate HOr22 groups

bonded to the same transition metal are neutral polymers obtained

by hydrothermal synthesis.12

When NiCl2 and orotic acid are reacted in a 1 : 2 ratio in

the presence of CsOH,{ the dianionic bis-orotate chelate with

aUniversity of Zaragoza, C.S.I.C., Department of Inorganic Chemistryand Aragon Materials Science Institute, Zaragoza, Spain.E-mail: falvello@unizar.es; Fax: 34 976761187; Tel: 34 976 761179bServicios Tecnicos de Investigacion, Facultad de Ciencias Fase II, 03690S. Vicente de Raspeig, Alicante, Spain. E-mail: tatiana.soler@ua.es Fig. 1 Orotic Acid.

COMMUNICATION www.rsc.org/crystengcomm | CrystEngComm

852 | CrystEngComm, 2007, 9, 852–855 This journal is � The Royal Society of Chemistry 2007

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trans-dispositions of all ligands is isolated as Cs2[trans-Ni(HOr)2-

(H2O)2]?4H2O (1), Fig. 2. X-Ray diffraction analysis{ reveals a

centrosymmetric complex with the two chelating orotates in the

basal plane and two aqua ligands in the axial positions. One of the

useful particulars of this complex is its anionic character. Anionic

compounds are rare among structurally characterized orotate

complexes and are mainly complexes of metals in oxidation states

other than +2 – oxidation state 0 (Cr, W),13 +1 (Rh, Ir),14

+3 (Fe).11 [Cu(HOr)(NH2CH2COO)(H2O)]2 is the only struc-

turally characterized anionic M+2 orotate compound.15 The

anionic character, among other things, enables a systematic study

of the product- and structure-directing influence of non-covalent

forces, which can be varied by changing the counterion.

If Cs+ is substituted in the synthesis by the bulky nBu4N+

cation,§ capable of forming only weak non-covalent interactions,

the product is an aqua-cis-isomer," isolated as (NBu4)2[cis-

Ni(HOr)2(H2O)2]?2H2O (2), Fig. 3.IApart from their overall shapes, there are no major geometrical

differences in the covalent structures of (1) and (2). There are slight

variations in the Ni–L distances, which can be described through a

comparison with the previously reported neutral mono-orotato

complex [Ni(HOr)(H2O)4]?H2O.16 The anionic trans-isomer (1) has

the Ni–N distance [2.0922(15) A] slightly elongated with respect to

that found for the neutral complex [2.059(1) A], while the Ni–O

(orotate) distances do not vary [2.0264(12) and 2.023(1) A,

respectively]. For the cis-isomer (2), the Ni–N and Ni–O distances

for one of the orotate ligands are slightly elongated [both are

2.070(3) A] with respect to those in the neutral complex, while the

analogous distances for the second chelate [2.053(3) and 2.029(3) A]

are identical within experimental error between the anionic and

neutral complexes.

However, the non-covalent interactions are very different for (1)

and (2). The relative dispositions of the ligands in the cis-isomer (2)

permit the formation of two intramolecular hydrogen bonds, in

each of which an aqua ligand serves as a donor and the proximal

carbonyl oxygen atom of the uracilate fragment is the acceptor

(Fig. 3).** In addition, in (2) one H atom of an aqua ligand

(H2WA, attached to O2W), makes a contact of 2.71(5) A with the

center of gravity (Cg) of the chelate ring [Ni1/O5/C7/C6/N1] of the

same molecule. The trans-isomer (1) does not present any

intramolecular hydrogen bonds or H…Cg contacts.

Moreover, the remaining functional groups of one orotate

ligand in (2), namely the imine at the 3-position [N(3)] and the

carbonyl at the 4-position, O(4), are involved in intermolecular

self-recognition with a neighboring molecule at (12x, 2y, 2z),

forming a ring of R22(8) topology17 (Fig. 4). The second orotate

forms a second link, via a symmetry-related pair of hydrogen

bonds from N(13) to the ligated carboxyl oxygen of its congener at

(22x, 2y, 12z) [R22(12), Fig. 4]. In this way, and together with the

nickel atoms, an unbounded chain of anions is formed. Parallel

chains are cross-linked by hydrogen-bonded, unligated water

molecules, giving a 2-D aggregate which is stacked along the [101]

direction to leave open channels in which the nBu4N+ cations

reside (Fig. 5).

The all-trans isomer (1) displays an entirely different behavior

(Fig. 6), forming electrostatic interactions with the cesium atom

and interstitial water molecules. These interactions dominate and

obviate the formation of orotate self-recognition interactions,

although there is a single unique p–p interaction between

neighboring pyrimidine rings.

It is clear from a comparison of (1) and (2) that the presence of

large groups with little capacity for forming directed non-covalent

interactions favors aggregation by self-recognition. These results

demonstrate, further, that it is possible to select among geometrical

isomers when the number of atoms that can participate in directed

non-covalent interactions is a large fraction of the total number

of non-hydrogen ligand atoms. This conclusion has important

impli-cations for the design of procedures aimed at selecting

isomers in the preparation of molecular solids.

Further investigation is needed to determine whether the present

results are obtained by selection during the crystallization process,

or whether significant aggregation already occurs in solution for

one or both cases.

The anionic bis-orotate chelate complexes are expected to be

useful in several interesting applications, from the study of non-

covalent interactions—as here—to the obtention of solids with

varying properties of interest for physical or even medical

applications. Their ionic nature is particularly useful in this

context, because it enables the use of the counterion topology as a

further variable parameter for structure direction, as well as the use

of the anionic complex as a building block for the formation of

heterometallic structures.

Fig. 2 Representation of the anion in Cs2[trans-Ni(HOr)2(H2O)2]?4H2O,

(1).

Fig. 3 Drawing of the anion from the crystal structure of (nBu4N)2[cis-

Ni(HOr)2(H2O)2]?2H2O, (2).

Fig. 4 Chain formed by three [Ni(HOr)2]2- fragments linked by

hydrogen bonds between orotate groups in complex 2.

This journal is � The Royal Society of Chemistry 2007 CrystEngComm, 2007, 9, 852–855 | 853

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Funding from the Ministry of Education and Science of Spain

(Grant CTQ2005-03141) is gratefully acknowledged.

Notes and references

{ Preparation of (1): The addition of 0.168 g (1.27 mmol) of NiCl2 to anaqueous solution of 0.45 g (2.53 mmol) of H3Or?H2O and 4.65 mmol ofCsOH produced the precipitation of complex (1) after 6 h of stirring. Theblue solid was filtered and washed with isopropanol, 71% yield. Elementalanalysis calcd (%): C 16.21, H 2.16, N 7.56; found: C 16.39, H 2.35, N 7.56.IR: 3509, 3458, 3252, 3143, 1605, 1552, 1489, 1373, 1017, 953, 802, 775,528 cm21. Crystals suitable for X-ray diffraction studies were obtainedfrom an aqueous solution of complex 1 layered with isopropanol.{ Crystallographic data for (1): Cs2[Ni(HOr)2(H2O)2]?4H2O,C10H16Cs2N4NiO14, M = 740.80, triclinic, P-1, a = 7.1982(5), b =8.6340(6), c = 9.2042(7) A, a = 105.813(1), b = 99.892(1), c = 112.181(1)u,V = 484.83(10) A3, Z = 1, F(000) = 354, r = 2.537 g cm23, m = 4.783 mm21,

T = 100(1) K, total of 6020 reflections, 2299 unique reflections (Rint =0.0156), 2243 observed reflections [I . 2s(I)], R1(obs) = 0.0140, R1(all) =0.0147, wR2(all) = 0.0363. Structure solution by direct methods. Allhydrogen atoms were located in a difference Fourier map and refined freelywith isotropic displacement parameters. CCDC reference number 649149.For crystallographic data in CIF or other electronic format see DOI:10.1039/b709168k§ Preparation of (2): An aqueous solution of 0.200 g (1.15 mmol) ofH3Or?H2O, 4.2 ml of NBu4OH (2.3 mmol) in MeOH and 0.074 g(0.58 mmol) of NiCl2 was allowed to stand for 24 h at 6 uC.; then it wasfiltered, taken to dryness and dissolved in isopropanol. The slowevaporation of the isopropanol solution produced crystals suitable for anX-ray diffraction study. IR: 3500, 2960, 1643, 1623, 1584, 1564, 1465, 1363,1314, 1019, 878, 785 cm21." With two aqua ligands and two hybrid (N, O) chelates, six geometricisomers are possible. We can describe them as cis- or trans- with respect tothe three types of ligating atoms, in the following order: (1) O(aq); (2)N(Or); (3) O(Or). Compound (1) is the all-trans or ttt isomer, and

Fig. 5 Aggregate formed by the [cis-Ni(HOr)2(H2O)2]22 anion in 2, with the atoms of the (nBu4N

+) cations, shown as spheres of radius 0.9 A, residing in

the channels formed.

Fig. 6 Two-dimensional net formed by the supramolecular aggregation of [trans-Ni(HOr)2(H2O)2]22 anions. The Cs+ cations are shown in space-filling

form with atoms represented by spheres of radius 1.0 A.

854 | CrystEngComm, 2007, 9, 852–855 This journal is � The Royal Society of Chemistry 2007

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compound (2) is cis- for the oxygen ligands and trans-for nitrogen (ctc). Tokeep the present discussion simple, we use the dispositions of themonodentate aqua ligands to distinguish between trans-(1) and cis-(2).I Crystallographic data for (2): (nBu4N)2[Ni(HOr)2(H2O)2]?2H2O,C42H84N6NiO12, M = 923.86, triclinic, P-1, a = 12.1915(4), b =12.3098(6), c = 16.4178(7) A, a = 90.374(4), b = 96.009(3), c =95.849(3)u, V = 2437.24(18) A3, Z = 2, F(000) = 1004, r = 1.259 g cm23,m = 0.461 mm21, T = 100(2) K, total of 19690 reflections, 8544 uniquereflections (Rint = 0.0547), 6734 observed reflections [I . 2s(I)], R1(obs) =0.0758, R1(all) = 0.1034, wR2(all) = 0.1422. Structure solution by directmethods. Orotate H atoms and methylene H atoms of the cations wereplaced in calculated positions and refined as riders with Uiso set to 1.2 timesUeq of their parent atoms. Methyl H atoms of the cation were treatedsimilarly except that they were located in slant Fourier calculations andrefined as riders with a variable torsion angle for the methyl group as awhole. Bound water H atoms were refined freely. For the unligated waterat O3W, the hydrogen atoms were not located. For the unligated water atO4W, H atoms were located and refined with free positional parametersbut with Uiso constrained to 1.2 times Ueq of O4W. CCDC referencenumber 649150. For crystallographic data in CIF or other electronicformat see DOI: 10.1039/b709168k** One such intramolecular H-bond could exist for the other possible cis-aqua arrangement, the (ccc) isomer; but the ligand arrangement would notfavor two such interactions.

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