N-Phenethyl­biguanidium tetra­chloro­zincate(II)

The title compound, (C₁₀H₁₇N₅)[ZnCl₄], was crystallized from an aqueous solution (pH 2) containing a 1:1 molar ratio of ZnCl₂ and 1-phenethyl­biguanide hydro­chloride. The geom­etry of the tetra­chloro­zincate(II) anion is a slightly distorted tetrahedron. The N-phenethyl­biguanidium divalent cation is diprotonated at the two imino groups, resulting in an intramolecular N—H...N hydrogen bond, which stabilizes the conformation of the cation in the structure. The dihedral angle between the two guanidine groups is 48.7 (2)°.

Key indicators

• Single-crystal X-ray study
• T = 173 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.031
• wR factor = 0.063
• Data-to-parameter ratio = 15.0

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level C:



PLAT_352  Alert C Short   N-H Bond (0.87A)   N(1)   -   H(15)  =       0.76 Ang.

PLAT_352  Alert C Short   N-H Bond (0.87A)   N(2)   -   H(14)  =       0.74 Ang.

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           25.50
         From the CIF: _reflns_number_total               3197
         Count of symmetry unique reflns         1908
         Completeness (_total/calc)            167.56%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured      1289
         Fraction of Friedel pairs measured     0.676
         Are heavy atom types Z>Si present          yes
          Please check that the estimate of the number of Friedel pairs is
          correct. If it is not, please give the correct count in the
          _publ_section_exptl_refinement section of the submitted CIF.


 0 Alert Level A = Potentially serious problem

 0 Alert Level B = Potential problem

 2 Alert Level C = Please check

---

S1. Comment

Phenformin (1-phenethylbiguanide hydrochloride) is a synthetic oral hypoglycemic agent used to control maturity-onset diabetes. Pharmacologically, phenformin acts to enhance anaerobic glycolysis, decrease gluconeogenesis, and inhibit intestinal absorption of glucose. Because studies have shown that phenformin has two negative side effects, lactic acidosis and shorter lifespans for patients taking phenformin, its use has decreased significantly (University Group Diabetes Program Research Group, 1975). In some countries, such as the US and most European countries, phenformin has been entirely withdrawn from the market. Most people now use metformin (1,1-dimethylbiguanide hydrochloride) when a biguanide is to be used. However, phenformin itself is still available in developing countries (Kwong & Brubacher, 1998; Haupt & Panten, 1997). Zinc also has many biological functions. It is considered to be an essential nutrient that is required for optimal growth and normal development of vertebrate organisms, as well as being important for maintaining the structure of many proteins. From previous research results, it has been known for many years that zinc mimics the actions of insulin on cells, including promotion of both lipogenesis and glucose transport. Zinc deficiency may indeed affect the optimal functioning of the insulin-signaling pathwway (Tang, 2001; Lynch, 2001; Coulston & Dandona, 1980; May & Contoreggi, 1982).

Our current research is aimed at preparing the zinc(II) complex of N-phenethylbiguanide similar to another biguanide complex (Zhu et al., 2002) in order to analyse the role of metal ions on antidiabetes agents because the monoprotonated, neutral and deprotonated molecules of the biguanides can function as mono- and bidentate ligands to form complexes with Zn^II, Cu^II and Ni^II (Zhu et al., 2002, 2002a,b). However, in this case, the N-phenethylbiguanidium did not act as a mono- or bidentate ligand to form the desired complex. Instead, the reaction produced a diprotonated divalent cation that formed a salt by cocrystalizing, at low pH, with a ZnCl₄²⁻ anion. Interestingly, we note that this is the first diprotonated N-phenethylbiguanidium to be studied in the solid state. The structures of two polymorphs of the chloride salt of the monoprotonatd form have been reported (Herrnstadt et al., 1979; Soriano-Lesh et al., 1998). In these monprotonated salts, there are two independent N-phenethylbiguanidinium cations in the asymmetric unit that form hydrogen-bonded dimers.

Selected geometric parameters are listed in Table 1, and a perspective view of the structure is shown in Fig. 1. In the title complex, (I), the site of diprotonation (at the two imino groups) and the conformation of the cation are different from monoprotonated (at the terminal imino group) biguanide derivatives, such as (C₄H₁₂N₅)[ZnCl₃] (Zhu et al., 2002), (C₆H₁₄N₅O)[ZnCl₃] (Yang & Zhu, 1991, 1992), C₁₀H₁₆N₅⁺·Cl⁻ (Herrnstadt et al., 1979; Soriano-Lesh et al., 1998), (C₄H₁₂N₅)[TlBr₄] (He et al., 2002), C₄H₁₂N₅⁺·Cl⁻ (Hariharan et al., 1989). All the C—N bond distances in (I) are shorter than single bonds and longer than double bonds, indicating a delocalization of π-electron density across the biguanide group. In addition, the molecules in the crystal are held together by a number of intermolecular N—H···Cl interactions (Desiraju, 1991). A weak N—H···N intramolecular hydrogen bond stabilizes the cation conformation (Fig. 1). Hydrogen-bond parameters are listed in Table 2, and a packing diagram is shown in Fig. 2.

In the structure of (I), atom N3 is a bridging N atom linking the two guanidine groups of the cation. The C9—N3—C10 angle [127.2 (3)°] is larger than found in the other biguanide derivatives listed in Table 3. As a result of protonation, there is a notable difference in the planar angle between the two guanidine groups in mono- and diprotonated residues. Namely, the dihedral angle in compound (I) is smaller than those in the monoprotonated biguanides and obviously larger than that of bidentate chelated forms. The central angle of the C–N–C chain in (I) is the largest of all the biguanidines listed in Table 3.

S2. Experimental

Crystals of (I) were grown from an aqueous solution at pH 2 of zinc(II) dichloride dihydrate (1.0 mmol) and N-phenethylbiguanide hydrochloride (1.0 mmol). The solution was left at room temperature and crystals formed after one to three months. The elemental analysis result was in agreement with the structural composition of (I).

S3. Refinement

H atoms attached to C atoms were placed in geometrically idealized positions, with Csp²—H = 0.99 Å and Csp³—H = 0.95 Å, and constrained to ride on their parent atoms, with U_iso(H) = 1.2U_eq(C). H atoms on N atoms were located in difference Fourier maps and refined with U_iso = 0.01–0.08 Ų and N–H distances in the range 0.74–0.89 Å.

Computing details

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2000); program(s) used to refine structure: SHELXL97 (Sheldrick, 2000); molecular graphics: SHELXTL/PC (Sheldrick, 1999); software used to prepare material for publication: SHELXTL/PC.

Figures

	Fig. 1. A view of the asymmetric unit of (I), with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radii. The dotted lines represent hydrogen bonds.
	Fig. 2. A packing diagram of the structure of the title compound.
	Fig. 3. Projection of the crystal structure of (I) along the a axis. The dotted lines represent hydrogen bonds.

N-phenethylbiguanidium tetrachlorozinc(II)

Crystal data

(C10H17N5)[ZnCl4]	F(000) = 840
Mr = 414.46	Dx = 1.582 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 4240 reflections
a = 6.6088 (10) Å	θ = 2.8–26.4°
b = 7.5837 (12) Å	µ = 2.02 mm^−1
c = 34.710 (5) Å	T = 173 K
V = 1739.6 (5) Å^3	BLOCK, colourless
Z = 4	0.40 × 0.40 × 0.30 mm

Data collection

Bruker SMART 1K CCD area-detector diffractometer	3197 independent reflections
Radiation source: fine-focus sealed tube	3064 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.025
ω scans	θmax = 25.5°, θmin = 2.4°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −7→8
Tmin = 0.467, Tmax = 0.545	k = −9→6
7460 measured reflections	l = −42→35

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.031	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.063	w = 1/[σ^2(Fo^2) + (0.0307P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max = 0.001
3197 reflections	Δρmax = 0.39 e Å^−3
213 parameters	Δρmin = −0.23 e Å^−3
0 restraints	Absolute structure: Flack (1983), 1291 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.010 (12)

Special details

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
Zn1	0.42267 (6)	0.57556 (5)	0.160470 (10)	0.03038 (11)
Cl1	0.40008 (12)	0.83552 (11)	0.19134 (2)	0.03182 (18)
Cl2	0.28585 (12)	0.36172 (10)	0.19906 (2)	0.03039 (19)
Cl3	0.75808 (14)	0.51983 (12)	0.15375 (3)	0.0550 (3)
Cl4	0.27058 (14)	0.57135 (12)	0.10251 (2)	0.0366 (2)
C1	0.5955 (5)	0.0660 (5)	0.06628 (9)	0.0313 (7)
C2	0.7083 (5)	0.2076 (5)	0.05367 (9)	0.0343 (8)
H2	0.6991	0.3174	0.0667	0.041*
C3	0.8357 (5)	0.1907 (6)	0.02188 (10)	0.0406 (9)
H3	0.9115	0.2891	0.0131	0.049*
C4	0.8511 (5)	0.0319 (6)	0.00342 (10)	0.0473 (11)
H4	0.9397	0.0199	−0.0180	0.057*
C5	0.7402 (6)	−0.1097 (6)	0.01554 (11)	0.0548 (11)
H5	0.7497	−0.2189	0.0022	0.066*
C6	0.6131 (6)	−0.0941 (6)	0.04737 (10)	0.0454 (9)
H6	0.5384	−0.1934	0.0561	0.055*
C7	0.4499 (5)	0.0859 (5)	0.09968 (8)	0.0336 (8)
H7A	0.4895	0.1897	0.1153	0.040*
H7B	0.4589	−0.0196	0.1164	0.040*
C8	0.2326 (5)	0.1086 (4)	0.08611 (8)	0.0290 (7)
H8A	0.2272	0.2009	0.0660	0.035*
H8B	0.1843	−0.0032	0.0746	0.035*
C9	−0.0093 (4)	0.0533 (4)	0.13881 (8)	0.0239 (7)
C10	−0.1599 (4)	0.0702 (5)	0.20336 (9)	0.0261 (7)
N1	−0.2919 (4)	0.1544 (4)	0.22408 (9)	0.0324 (7)
N2	−0.0547 (5)	−0.0600 (5)	0.21745 (9)	0.0398 (8)
N3	−0.1301 (4)	0.1290 (4)	0.16681 (7)	0.0262 (6)
N4	−0.0197 (5)	−0.1186 (4)	0.13340 (9)	0.0317 (7)
N5	0.1001 (4)	0.1581 (4)	0.11811 (8)	0.0286 (6)
H9	0.113 (4)	0.251 (4)	0.1267 (8)	0.010 (8)*
H10	−0.102 (5)	−0.170 (5)	0.1460 (9)	0.030 (10)*
H11	0.059 (8)	−0.177 (7)	0.1194 (12)	0.083 (17)*
H12	−0.170 (5)	0.239 (5)	0.1645 (10)	0.035 (10)*
H13	0.062 (6)	−0.100 (5)	0.2091 (9)	0.039 (10)*
H14	−0.085 (5)	−0.097 (5)	0.2363 (9)	0.023 (9)*
H15	−0.364 (4)	0.222 (4)	0.2152 (8)	0.003 (8)*
H16	−0.314 (5)	0.118 (5)	0.2480 (11)	0.043 (11)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Zn1	0.0307 (2)	0.02508 (19)	0.0354 (2)	0.00142 (18)	0.00518 (18)	0.00062 (18)
Cl1	0.0356 (4)	0.0264 (4)	0.0335 (4)	0.0010 (4)	−0.0005 (4)	−0.0018 (3)
Cl2	0.0302 (4)	0.0297 (4)	0.0313 (4)	−0.0034 (4)	0.0030 (3)	0.0007 (3)
Cl3	0.0326 (5)	0.0254 (4)	0.1070 (9)	0.0041 (4)	0.0220 (5)	0.0115 (5)
Cl4	0.0505 (5)	0.0293 (4)	0.0299 (4)	0.0027 (4)	0.0045 (4)	−0.0013 (4)
C1	0.0236 (15)	0.041 (2)	0.0292 (16)	0.0069 (18)	−0.0040 (14)	0.0036 (16)
C2	0.0337 (19)	0.035 (2)	0.0340 (19)	0.0042 (17)	−0.0072 (15)	0.0025 (15)
C3	0.0320 (19)	0.053 (3)	0.037 (2)	−0.0017 (18)	−0.0020 (15)	0.0117 (19)
C4	0.037 (2)	0.072 (3)	0.033 (2)	−0.002 (2)	0.0091 (16)	−0.007 (2)
C5	0.057 (2)	0.053 (3)	0.054 (2)	−0.008 (2)	0.019 (2)	−0.018 (2)
C6	0.046 (2)	0.044 (2)	0.046 (2)	−0.014 (2)	0.0113 (17)	−0.0072 (19)
C7	0.0314 (18)	0.042 (2)	0.0280 (17)	0.0041 (17)	0.0017 (14)	0.0039 (16)
C8	0.0330 (17)	0.0295 (19)	0.0246 (16)	−0.0049 (16)	0.0039 (13)	0.0007 (14)
C9	0.0228 (15)	0.0241 (18)	0.0248 (16)	−0.0004 (14)	−0.0048 (13)	−0.0029 (14)
C10	0.0209 (15)	0.0274 (17)	0.0300 (17)	−0.0050 (15)	−0.0005 (12)	−0.0025 (16)
N1	0.0312 (17)	0.0350 (17)	0.0311 (17)	0.0088 (16)	0.0041 (14)	0.0042 (14)
N2	0.0371 (19)	0.049 (2)	0.0331 (18)	0.0143 (17)	0.0110 (15)	0.0158 (16)
N3	0.0281 (14)	0.0206 (15)	0.0301 (15)	0.0017 (12)	0.0035 (11)	0.0005 (12)
N4	0.0354 (17)	0.0244 (17)	0.0352 (17)	−0.0037 (14)	0.0044 (14)	−0.0002 (14)
N5	0.0318 (15)	0.0214 (15)	0.0327 (15)	−0.0039 (14)	0.0039 (13)	−0.0030 (13)

Geometric parameters (Å, º)

Zn1—Cl1	2.2487 (9)	C7—H7B	0.9900
Zn1—Cl4	2.2492 (9)	C8—N5	1.463 (4)
Zn1—Cl3	2.2686 (10)	C8—H8A	0.9900
Zn1—Cl2	2.2894 (9)	C8—H8B	0.9900
C1—C2	1.378 (5)	C9—N5	1.292 (4)
C1—C6	1.386 (5)	C9—N4	1.319 (4)
C1—C7	1.515 (4)	C9—N3	1.382 (4)
C2—C3	1.394 (5)	C10—N1	1.298 (4)
C2—H2	0.9500	C10—N2	1.303 (4)
C3—C4	1.368 (5)	C10—N3	1.359 (4)
C3—H3	0.9500	N1—H15	0.77 (3)
C4—C5	1.367 (6)	N1—H16	0.89 (4)
C4—H4	0.9500	N2—H13	0.88 (4)
C5—C6	1.393 (5)	N2—H14	0.74 (3)
C5—H5	0.9500	N3—H12	0.88 (4)
C6—H6	0.9500	N4—H10	0.80 (4)
C7—C8	1.521 (4)	N4—H11	0.84 (5)
C7—H7A	0.9900	N5—H9	0.77 (3)
Cl1—Zn1—Cl4	114.14 (3)	H7A—C7—H7B	107.9
Cl1—Zn1—Cl3	106.09 (4)	N5—C8—C7	111.0 (2)
Cl4—Zn1—Cl3	110.00 (4)	N5—C8—H8A	109.4
Cl1—Zn1—Cl2	108.42 (3)	C7—C8—H8A	109.4
Cl4—Zn1—Cl2	109.68 (3)	N5—C8—H8B	109.4
Cl3—Zn1—Cl2	108.30 (4)	C7—C8—H8B	109.4
C2—C1—C6	119.2 (3)	H8A—C8—H8B	108.0
C2—C1—C7	120.6 (3)	N5—C9—N4	123.9 (3)
C6—C1—C7	120.2 (3)	N5—C9—N3	117.3 (3)
C1—C2—C3	120.4 (3)	N4—C9—N3	118.7 (3)
C1—C2—H2	119.8	N1—C10—N2	121.5 (3)
C3—C2—H2	119.8	N1—C10—N3	117.0 (3)
C4—C3—C2	119.8 (4)	N2—C10—N3	121.4 (3)
C4—C3—H3	120.1	C10—N1—H15	122 (2)
C2—C3—H3	120.1	C10—N1—H16	119 (2)
C5—C4—C3	120.5 (3)	H15—N1—H16	118 (3)
C5—C4—H4	119.8	C10—N2—H13	127 (2)
C3—C4—H4	119.8	C10—N2—H14	118 (3)
C4—C5—C6	120.1 (4)	H13—N2—H14	113 (3)
C4—C5—H5	120.0	C10—N3—C9	127.2 (3)
C6—C5—H5	120.0	C10—N3—H12	111 (2)
C1—C6—C5	120.0 (4)	C9—N3—H12	120 (2)
C1—C6—H6	120.0	C9—N4—H10	116 (3)
C5—C6—H6	120.0	C9—N4—H11	125 (3)
C1—C7—C8	112.0 (2)	H10—N4—H11	119 (4)
C1—C7—H7A	109.2	C9—N5—C8	126.8 (3)
C8—C7—H7A	109.2	C9—N5—H9	114 (2)
C1—C7—H7B	109.2	C8—N5—H9	118 (2)
C8—C7—H7B	109.2
C6—C1—C2—C3	1.1 (5)	C6—C1—C7—C8	−78.7 (4)
C7—C1—C2—C3	−177.2 (3)	C1—C7—C8—N5	−170.1 (3)
C1—C2—C3—C4	−1.0 (5)	N1—C10—N3—C9	−175.0 (3)
C2—C3—C4—C5	1.0 (6)	N2—C10—N3—C9	7.8 (5)
C3—C4—C5—C6	−1.3 (6)	N5—C9—N3—C10	−137.8 (3)
C2—C1—C6—C5	−1.4 (6)	N4—C9—N3—C10	45.7 (5)
C7—C1—C6—C5	177.0 (3)	N4—C9—N5—C8	−1.2 (5)
C4—C5—C6—C1	1.4 (6)	N3—C9—N5—C8	−177.5 (3)
C2—C1—C7—C8	99.6 (4)	C7—C8—N5—C9	−95.5 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H16···Cl1^i	0.89 (4)	2.73 (4)	3.319 (3)	125 (3)
N1—H16···Cl2^i	0.89 (4)	2.68 (4)	3.471 (4)	148 (3)
N3—H12···Cl3^ii	0.88 (4)	2.21 (4)	3.088 (3)	173 (3)
N4—H11···Cl4^iii	0.84 (5)	2.44 (5)	3.219 (3)	155 (4)
N1—H15···Cl2^ii	0.77 (3)	2.60 (3)	3.319 (3)	156 (3)
N5—H9···Cl2	0.77 (3)	2.89 (3)	3.433 (3)	130 (3)
N5—H9···Cl4	0.77 (3)	2.77 (3)	3.374 (3)	137 (3)
N2—H14···Cl2^i	0.74 (3)	2.63 (3)	3.330 (4)	160 (3)
N2—H13···Cl1^iii	0.88 (4)	2.37 (4)	3.237 (3)	170 (3)
N4—H10···N2	0.80 (4)	2.63 (3)	2.960 (5)	106 (3)

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