Bis(1,1-di­methyl­biguanido)copper(II) octahydrate

A complex of a deprotonated form of metformin with Cu²⁺, [Cu(C₄H₁₀N₅)₂]·8H₂O, was prepared from alkaline aqueous solution. The coordination geometry around the Cu atom is square planar, with four N atoms from two bidentate ligands. The deprotonation of the ligand causes an increase in the π conjugation of the C—N—C system, reducing the bond angle at the central N atom to nearly 120°. The dihedral angle between the two six-membered chelate rings in the complex is 11.31 (5)°. The Cu atom lies on a twofold rotation axis.

Key indicators

• Single-crystal X-ray study
• T = 173 K
• Mean [sigma](N-C) = 0.002 Å
• R factor = 0.026
• wR factor = 0.051
• Data-to-parameter ratio = 13.8

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


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S1. Comment

Metformin (1,1-dimethylbiguanide) has been introduced as an oral glucose-lowering agent for the treatment of non-insulin dependent diabetes mellitus. Like biguanide, it is a moderately strong base, forming well defined salts and possessing excellent capacity for coordination with transition metals, giving rise to highly colored bidentate chelate complexes. Various metal complexes have been studied, such as [PtCl(C₄H₁₁N₅)(DMSO)]Cl (Viossat et al., 1995), [PtCl₄(C₄H₁₁N₅)(DMSO)] (Bentefrit et al., 1997), [Co(C₄H₁₂N₅)Cl₃], [CuCl₂(C₄H₁₁N₅)₂], [Cu(C₄H₁₁N₅)₂]Cl₂·2H₂O, [Ni(C₄H₁₁N₅)₂](Cl)(OH) (Lemoine et al., 1996), and [Zn(C₄H₁₂N₅)Cl₃] (Zhu, Lu, Jin & Yang, 2002) (DMSO is dimethyl sulfoxide). The metal complexes of biguanide ligands are usually cationic in nature, and their color varies with the nature of the metal ion and its oxidation state, as well as with the number of ligands in the complex. It has been found that the bidentate ligand can chelate to metals in a square-planar configuration through four N atoms of two ligands. Here, we report the synthesis of a red copper complex of a deprotonated form, (I), of metformin (an anionic ligand) and its crystal structure.

The geometric parameters of (I) are listed in Table 1. The molecular conformation and crystal packing are illustrated in Figs. 1 and 2. The structure can be regarded as a square-planar coordination of the metal ion through the formation of four M—N bonds with two bidentate ligands. The central metal atom lies on a crystallographic twofold rotation axis. The two ligands form a slightly distorted plane with the Cu at the center. The dimethyl groups of the two ligands have a trans configuration.

The Cu—N bond distances in the structure of (I) are worthy of comment. The values 1.9210 (14) and 1.9428 (13) Å are very similar to those of 1.920 (4) and 1.931 (4) Å in [Cu(C₄H₁₁N₅)₂]·2HCO₃, and 1.932 (7) and 1.948 (7) Å in [Cu(C₄H₁₁N₅)₂]Cl₂·2H₂O (Viossat et al., 1995; Lemoine et al., 1996). They are significantly longer than the Ni—N bonds in [Ni(C₄H₁₁N₅)₂] (Zhu, Lu, Yang & Jin, 2002), [1.8478 (17) and 1.8541 (16) Å] and in [Ni(C₄H₁₁N₅)₂](Cl)(OH) (Lemoine et al., 1996) [1.863 (5) and 1.866 (5) Å]. This large difference is considered to be a result of the removal of an unpaired electron from the d(x²-y²) orbital of the d⁹ configuration of Cu²⁺ on going to the low-spin d⁸ configuration of Ni²⁺, in addition to the small ionic radius difference of Ni²⁺ (0.55) and Cu²⁺ (0.57) for all coordination numbers (Shannon, 1976).

Another interesting feature in the ligand geometry is the effect of deprotonation. The C—N bond lengths involving the coordinating N atoms of the deprotonated biguanide moiety are 1.3060 (19) and 1.3125 (19) Å. These show delocalization with the C—N4 bonds of 1.3503 (19) and 1.372 (2) Å. Deprotonation of the ligand produces an increase of the π conjugation, reducing the bond angle at N4 to 121.04 (13)°, compared with 124.9 (8)–127.7 (5)° for neutral ligands (Bentefrit et al., 1997; Lemoine et al., 1996).

The dihedral angle between the two chelate rings in (I) is 11.31 (5)°. This is larger than that in [Ni(C₄H₁₁N₅)₂] (Zhu, Lu, Yang & Jin, 2002) [0.02 (7)°], and may be due to the larger ionic radius of Cu²⁺. The crystal packing is characterized by 11 intermolecular hydrogen bonds involving N2, N3, and N4 of the metformin as well as all O atoms of solvent water molecules.

S2. Experimental

1,1-Dimethylbiguanide hydrochloride was purchased from the Wujin Medicine Raw Material Chemical Factory of China. CuCl₂·2H₂O was a commercial sample from Acros, and was used without further purification. An aqueous solution of CuCl₂·2H₂O was added dropwise to 0.1 M KOH solution of the ligand with stirring, in the mole ratio 1:2. The red solution was filtered, and the filtrate was left at room temperature. Red crystals were formed after a few days. The elemental analyses results are in agreement with the structural composition of (I).

S3. Refinement

Methyl H atoms were treated as riding, with C—H = 0.96 Å and U_iso(H) = 1.5U_eq(C). The H atoms on N or O atoms were refined, with U_iso(H) = 0.03 Ų (0.08 for O); N—H distances are in the range 0.81—0.89 Å and the O—H distances are in the range 0.78–0.84 Å.

Computing details

Data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1994); cell refinement: MSC/AFC Diffractometer Control Software; data reduction: MSC/AFC Diffractometer Control Software; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP (Siemens, 1990); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. A view of the molecular structure of (I) with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. The packing of the title compound, viewed approximately down the b axis.

Bis(1,1-dimethylbiguanido)copper(II) octahydrate

Crystal data

[Cu(C4H10N5)2]·8H2O	F(000) = 988
Mr = 464.01	Dx = 1.472 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 9440 reflections
a = 23.561 (5) Å	θ = 3.1–27.5°
b = 6.952 (1) Å	µ = 1.10 mm^−1
c = 13.297 (3) Å	T = 173 K
β = 105.95 (3)°	Block, red
V = 2094.1 (7) Å^3	0.50 × 0.40 × 0.25 mm
Z = 4

Data collection

Rigaku RAXIS RAPID IP diffractometer	2381 independent reflections
Radiation source: fine-focus sealed tube	1894 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.032
Detector resolution: 100x100 microns pixels mm^-1	θmax = 27.5°, θmin = 3.1°
ϕ scans	h = −30→30
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	k = −9→9
Tmin = 0.596, Tmax = 0.760	l = −17→16
2381 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.026	Hydrogen site location: hydrogen atoms are generated by HFIX instructions
wR(F^2) = 0.051	H atoms treated by a mixture of independent and constrained refinement
S = 0.90	w = 1/[σ^2(Fo^2) + (0.0242P)^2] where P = (Fo^2 + 2Fc^2)/3
2381 reflections	(Δ/σ)max = 0.008
173 parameters	Δρmax = 0.38 e Å^−3
0 restraints	Δρmin = −0.21 e Å^−3

Special details

Experimental. ABSCOR BY T·Higashi 8 march,1995

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Cu1	0.0000	0.30656 (4)	0.2500	0.01457 (8)
O1	0.14695 (5)	0.5913 (2)	0.01670 (9)	0.0259 (3)
O2	0.17243 (6)	−0.05680 (19)	0.11067 (10)	0.0258 (3)
O3	0.20797 (7)	0.7597 (2)	0.30342 (12)	0.0348 (3)
O4	0.23114 (7)	0.0324 (2)	0.46070 (12)	0.0359 (3)
N1	0.00087 (6)	0.2977 (2)	0.10439 (10)	0.0185 (3)
N2	0.08473 (6)	0.3139 (2)	0.28720 (10)	0.0208 (3)
N3	0.17916 (6)	0.3333 (2)	0.26815 (11)	0.0213 (3)
N4	0.10350 (5)	0.27755 (18)	0.12070 (10)	0.0162 (3)
N5	0.03608 (6)	0.2209 (2)	−0.03835 (10)	0.0188 (3)
C1	0.04526 (7)	0.2672 (2)	0.06462 (12)	0.0153 (3)
C2	0.11909 (6)	0.3060 (2)	0.22517 (11)	0.0154 (3)
C3	0.08238 (7)	0.2029 (3)	−0.09095 (12)	0.0223 (3)
H3A	0.1201	0.2233	−0.0415	0.034*
H3B	0.0764	0.2970	−0.1457	0.034*
H3C	0.0812	0.0764	−0.1204	0.034*
C4	−0.02361 (7)	0.2050 (3)	−0.10674 (11)	0.0218 (3)
H4A	−0.0478	0.1362	−0.0713	0.033*
H4B	−0.0228	0.1369	−0.1692	0.033*
H4C	−0.0396	0.3313	−0.1249	0.033*
H11A	0.1491 (9)	0.693 (4)	0.0484 (17)	0.047 (7)*
H11B	0.1373 (8)	0.505 (4)	0.0505 (16)	0.044 (7)*
H12A	0.1522 (8)	0.034 (3)	0.1092 (15)	0.034 (6)*
H12B	0.1924 (10)	−0.035 (4)	0.0722 (18)	0.060 (8)*
H13A	0.1946 (10)	0.817 (3)	0.2469 (19)	0.052 (7)*
H13B	0.1995 (10)	0.650 (4)	0.2926 (18)	0.048 (8)*
H14A	0.2680 (11)	0.039 (4)	0.474 (2)	0.076 (9)*
H14B	0.2227 (10)	−0.056 (4)	0.4234 (18)	0.065 (9)*
H21	−0.0308 (8)	0.295 (3)	0.0590 (13)	0.020 (5)*
H22	0.1038 (7)	0.339 (2)	0.3499 (13)	0.020 (5)*
H23A	0.1995 (8)	0.303 (3)	0.2326 (14)	0.025 (5)*
H23B	0.1936 (8)	0.285 (3)	0.3317 (15)	0.027 (5)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cu1	0.01494 (14)	0.01703 (15)	0.01244 (14)	0.000	0.00494 (10)	0.000
O1	0.0337 (7)	0.0238 (7)	0.0201 (6)	−0.0062 (6)	0.0070 (5)	0.0019 (6)
O2	0.0296 (7)	0.0210 (7)	0.0290 (7)	0.0051 (6)	0.0119 (6)	0.0012 (6)
O3	0.0456 (9)	0.0294 (9)	0.0275 (8)	−0.0040 (7)	0.0068 (6)	−0.0009 (6)
O4	0.0325 (8)	0.0409 (9)	0.0379 (8)	−0.0080 (7)	0.0158 (6)	−0.0124 (7)
N1	0.0142 (6)	0.0255 (7)	0.0147 (6)	0.0001 (7)	0.0023 (5)	−0.0003 (6)
N2	0.0178 (6)	0.0312 (8)	0.0124 (6)	−0.0018 (7)	0.0027 (5)	−0.0019 (7)
N3	0.0155 (7)	0.0318 (9)	0.0169 (7)	0.0000 (6)	0.0050 (6)	−0.0002 (7)
N4	0.0161 (6)	0.0176 (7)	0.0151 (6)	−0.0007 (5)	0.0047 (5)	−0.0007 (5)
N5	0.0193 (6)	0.0240 (8)	0.0137 (6)	0.0010 (6)	0.0056 (5)	−0.0019 (6)
C1	0.0199 (7)	0.0115 (8)	0.0139 (7)	−0.0004 (6)	0.0039 (6)	0.0022 (6)
C2	0.0160 (7)	0.0125 (7)	0.0170 (7)	−0.0003 (7)	0.0032 (6)	0.0019 (7)
C3	0.0275 (8)	0.0244 (9)	0.0170 (8)	0.0006 (8)	0.0092 (6)	−0.0033 (8)
C4	0.0233 (8)	0.0246 (9)	0.0149 (7)	0.0006 (8)	0.0009 (6)	−0.0017 (7)

Geometric parameters (Å, º)

Cu1—N2^i	1.9210 (14)	N2—H22	0.849 (17)
Cu1—N2	1.9210 (14)	N3—C2	1.3861 (19)
Cu1—N1^i	1.9428 (13)	N3—H23A	0.789 (18)
Cu1—N1	1.9428 (13)	N3—H23B	0.886 (19)
O1—H11A	0.82 (2)	N4—C2	1.3503 (19)
O1—H11B	0.82 (2)	N4—C1	1.372 (2)
O2—H12A	0.79 (2)	N5—C1	1.3647 (19)
O2—H12B	0.80 (2)	N5—C3	1.4539 (19)
O3—H13A	0.83 (2)	N5—C4	1.454 (2)
O3—H13B	0.79 (2)	C3—H3A	0.960
O4—H14A	0.84 (2)	C3—H3B	0.960
O4—H14B	0.78 (3)	C3—H3C	0.960
N1—C1	1.3125 (19)	C4—H4A	0.960
N1—H21	0.820 (18)	C4—H4B	0.960
N2—C2	1.3060 (19)	C4—H4C	0.960
N2^i—Cu1—N2	176.96 (10)	C1—N5—C4	120.32 (12)
N2^i—Cu1—N1^i	87.86 (6)	C3—N5—C4	114.65 (12)
N2—Cu1—N1^i	92.24 (6)	N1—C1—N5	121.22 (14)
N2^i—Cu1—N1	92.24 (6)	N1—C1—N4	124.15 (14)
N2—Cu1—N1	87.86 (6)	N5—C1—N4	114.63 (13)
N1^i—Cu1—N1	176.39 (9)	N2—C2—N4	127.96 (13)
H11A—O1—H11B	110 (2)	N2—C2—N3	118.28 (14)
H12A—O2—H12B	107 (2)	N4—C2—N3	113.74 (13)
H13A—O3—H13B	106 (2)	N5—C3—H3A	109.5
H14A—O4—H14B	104 (2)	N5—C3—H3B	109.5
C1—N1—Cu1	129.38 (11)	H3A—C3—H3B	109.5
C1—N1—H21	111.3 (11)	N5—C3—H3C	109.5
Cu1—N1—H21	118.6 (11)	H3A—C3—H3C	109.5
C2—N2—Cu1	128.10 (11)	H3B—C3—H3C	109.5
C2—N2—H22	112.1 (11)	N5—C4—H4A	109.5
Cu1—N2—H22	119.3 (11)	N5—C4—H4B	109.5
C2—N3—H23A	115.8 (13)	H4A—C4—H4B	109.5
C2—N3—H23B	115.0 (12)	N5—C4—H4C	109.5
H23A—N3—H23B	109.4 (18)	H4A—C4—H4C	109.5
C2—N4—C1	121.04 (13)	H4B—C4—H4C	109.5
C1—N5—C3	124.75 (13)
N2—Cu1—N1—C1	12.15 (15)	C3—N5—C1—N4	−6.5 (2)
N2^i—Cu1—N1—C1	−170.89 (15)	C4—N5—C1—N4	179.93 (13)
N1^i—Cu1—N2—C2	174.01 (16)	C2—N4—C1—N1	5.3 (2)
N1—Cu1—N2—C2	−2.37 (16)	C2—N4—C1—N5	−174.39 (14)
Cu1—N1—C1—N5	164.27 (12)	Cu1—N2—C2—N4	−5.0 (3)
Cu1—N1—C1—N4	−15.4 (2)	Cu1—N2—C2—N3	173.56 (12)
C3—N5—C1—N1	173.82 (15)	C1—N4—C2—N2	5.1 (3)
C4—N5—C1—N1	0.2 (2)	C1—N4—C2—N3	−173.49 (14)

Symmetry code: (i) −x, y, −z+1/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H11A···O2^ii	0.82 (2)	1.94 (2)	2.737 (2)	165 (2)
O1—H11B···N4	0.82 (2)	2.10 (2)	2.9149 (19)	173 (2)
O2—H12A···N4	0.79 (2)	2.08 (2)	2.8597 (19)	174.3 (19)
O2—H12B···O4^iii	0.80 (2)	1.94 (2)	2.727 (2)	167 (2)
O3—H13A···O2^ii	0.83 (2)	1.95 (2)	2.778 (2)	173 (2)
O3—H13B···N3	0.79 (2)	2.26 (3)	3.049 (2)	177 (2)
O4—H14A···O1^iv	0.84 (2)	2.01 (3)	2.834 (2)	169 (3)
O4—H14B···O3^v	0.78 (3)	2.00 (3)	2.764 (2)	166 (2)
N2—H22···O1^vi	0.849 (17)	2.225 (17)	3.072 (2)	175.5 (15)
N3—H23A···O3^iv	0.789 (18)	2.376 (18)	3.103 (2)	153.7 (17)
N3—H23B···O4	0.886 (19)	2.444 (19)	3.272 (2)	155.8 (16)

Symmetry codes: (ii) x, y+1, z; (iii) x, −y, z−1/2; (iv) −x+1/2, y−1/2, −z+1/2; (v) x, y−1, z; (vi) x, −y+1, z+1/2.