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Electron density of the 1:2 complex of valinomycin with calcium triflate observed in crystals of the composition (valinomycin)Ca2(OTf)4(THF)5(H2O)4

  • Peter Luger and Birger Dittrich
Published/Copyright: August 11, 2022
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Zeitschrift für Naturforschung B
From the journal Zeitschrift für Naturforschung B Volume 77 Issue 9

Abstract

The electron density of a 1:2 complex of valinomycin with calcium triflate consisting of 10 substructures and a total of 279 atoms was examined using the invariom formalism. In addition to geometric properties, sites and strengths of hydrogen bonds were identified from bond topological properties and from electron density concentrations mapped onto Hirshfeld surfaces. In contrast to free valinomycin and corresponding complexes with potassium the hydrogen bonds are all intermolecular and evenly distributed over the complex. A series of electrostatic potential (ESP) surfaces show the mutual influence in the ensemble of this high Z′ structure.

Keywords: electron density; invariom formalism; macrolide antibiotic; valinomycin

1 Introduction

Valinomycin is a well-known macrolide antibiotic. Its complexes with potassium salts have the highly selective ability (compared to complexes with sodium salts) to penetrate lipid cell membranes. In the 2002/2003 SARS epidemic it was reported to be the most potent agent against the SARS corona virus (SARS CoV) [1, 2]. Whether or not it plays a role against SARS-CoV-2 in the present Covid-19 pandemic is not known to the authors, however, tests were apparently carried out for its potential activity in this context.

Valinomycin is an electroneutral cyclododecadepsipeptide of the composition (D-α-hydroxyisovaleryl-D-valyl-L-lactoyl-L-valyl)3. Determinations of crystal structures of valinomycin by single-crystal X-ray diffraction has been reported from 38 studies compiled in the Cambridge Structural Data Base (CSD, version 5.42, Nov. 2020) [3], of which 20 refer to non-coordinated derivatives and 18 to complexes with metal salts, in most cases with potassium. The first of these structures was already published in 1969 for the complex with potassium (valinomycin-potassium tetrachlorido-aurate) [4]. The first structure analyses on non-complexed valinomycin appeared almost at the same time in 1975, authored by Karle [5] and Duax et al. [6].

The first two complexes with calcium salts (the triflates) were published in 2017 [7] having the composition

  1. A: (valinomycin · 2OTf¯ · 2H2O · 2Ca2+)2+ · 2OTf¯ · 4(C2H3N), CSD code YALPEJ [3].

  2. B: (valinomycin · 2OTf¯ · 2H2O · 2Ca2+)2+ · 2OTf¯ · 5 THF · 2H2O, CSD code YALPIN [3].

(OTf = triflate = trifluoromethanesulfonate; C2H3N = acetonitrile).

In both cases accurate X-ray diffraction data sets to a resolution of (sin θ/λ)max = 0.73 Å−1 were published, and data was made available for download from the CSD [3]. Compound B, for which the crystals were reported to be free of disorder, raised our interest for an electron density (ED) study, because the interactions between the numerous charged and non-charged molecular fragments can be studied with acceptable effort on the level of the electron density distribution making use of the invariom formalism [8, 9]. The four formal charges of the two Ca2+ cations are compensated by the negative charges of the four OTf¯ anions, two of them directly involved in coordination to the metal cations. Five THF and two water solvent molecules complete this high Z′ crystal structure, so that various types of intermolecular contacts exist. In addition to atomic and bonding properties, electrostatic potential and Hirshfeld surfaces are provided below. They illustrate the intra- and intermolecular interactions.

2 Results and discussion

2.1 Comparison of intra and intermolecular geometry

Results of the crystal structure analysis have already been discussed in ref. [7]. For convenience and for a better understanding of the ED properties discussed below we repeat here some structural properties, respectively add a discussion of results which were not addressed in ref. [7] as for example hydrogen bonding details which were not completely listed in ref. [7] neither in the full text nor in the supporting information.

In the crystal structure we consider the following 10 groups for the invariom refinement:

  1. Group 1: the cationic partial structure (valinomycin · 2OTf¯ · 2H2O · 2Ca2+)2+,

  2. Groups 2 and 3: two OTf¯ anions,

  3. Group 4–8: five THF molecules,

  4. Groups 9 and 10: two water molecules.

The Group 1 cation is shown in Figure 1 in a Mercury representation [10]. We note that the cation of complex A mentioned above (and not considered here) has practically the same molecular geometry compared to B as shown in a graphical superposition (Schakal representation [11] in the Electronic Supporting Information available online (Figure S1)).

Figure 1: Molecular structure of the Group 1 cation, Mercury representation [10].
Figure 1:

Molecular structure of the Group 1 cation, Mercury representation [10].

In contrast to the complex with a potassium polyiodide salt reported in ref. [12], which contains a K+ cation in the cavity of the valinomycin molecule, the Ca complex has two Ca2+ ions embedded in the cavity of the valinomycin molecule. This leads to strong differences in the overall geometry of this cationic unit. The valinomycin molecule accommodating the potassium cation has been described to have a bracelet conformation [7], the cavity of which would be too small to provide the space for two metal ions. The graphical superposition in Figure 2 shows an almost circular shape of the valinomycin ligand around the potassium cation in the polyiodide salt [12] (green structure) compared to a more ellipsoidal shape of the complex unit where the valinomycin molecule surrounds two Ca2+ ions (red structure).

Figure 2: Graphical superposition of the Ca (red) and the K complex cations (green) [12]; Schakal stereo representation [11].
Figure 2:

Graphical superposition of the Ca (red) and the K complex cations (green) [12]; Schakal stereo representation [11].

Group 1 carries the formal charge +2, which is compensated by the Group 2 and 3 triflate anions. Five THF (Groups 4–8) and two further water molecules (Groups 9, 10) complete the content of the asymmetric unit. The latter play a role, for example, as hydrogen bond acceptors from Group 1 N–H donor groups.

Group 1 can be subdivided into the outer valinomycin dodecacycle and a “core” region consisting of the Ca cations and fragments contributing to their coordination sphere. Each calcium cation is octahedrally coordinated by six oxygen atoms. Axial oxygen atoms are provided from carbonyl groups of valerate residues for Ca1 and lactate residues for Ca2. Equatorial oxygen atoms are from water molecules in both cases and from lactate and valerate carbonyl oxygen atoms for Ca1 and Ca2, respectively. Two bridges between the Ca cations exist via the two triflate anions, which contribute two oxygen atoms each, so that the Ca coordination spheres are linked by two sequences Ca1–O–S–O–Ca2, see Figure 1. It follows that triflate anions and water molecules play a significant role in establishing the structure of Group 1.

2.2 Discussion of the invariom derived electron density properties

A summary of hydrogen bonding (HB) geometries and their electron-density derived properties [16] is given in Table 1. All six N–H groups of the valinomycin molecule are HB donors. The same holds for all O–H groups of the four water molecules, so that a total of 14 HBs exist. Critical points were localized on all HBs. It should be mentioned that Platon [13] reports 23 further C–H⋅⋅⋅X HBs (X = O, F) which we do not want to consider here. Of certain interest is the distribution of HB acceptors. Four of the five oxygen atoms in the THF molecules are acceptors, the fifth one belongs to the Group 8 THF molecule which we identified to be partially disordered. The two triflate groups involved in the Group 1 complex deliver two of their three oxygen atoms to the Ca coordination, as mentioned above. The remaining ones are acceptors of HBs from two water oxygen atoms, and all oxygen atoms of the triflate Groups 2 and 3 are HB acceptors. Finally, two water oxygen atoms are acceptors of O–H···O HBs. This acceptor distribution is in strict contrast to the HB pattern in the K complex [12] and in non-complexed valinomycin [5] where all six N–H···O HBs are intramolecular.

Table 1:

Summary of hydrogen bonding geometries and their electron-density derived properties (with data from Platon [13] and XDProp. [14]).

D–H⋅⋅⋅A D⋅⋅⋅A (Å) H⋅⋅⋅A (Å) D–H⋅⋅⋅A (deg) ρ(rBCP) (e Å−3) ∇2ρ(rBCP) (e Å−5) Accept. Group EHB (kJ mol−1)e
N(1)–H(1N)⋅⋅⋅O(27T)a 2.915(2) 1.928(2) 166.4(2) 0.15 2.29 G2 OTf 23.64
N(2)–H(2N)⋅⋅⋅O(33F) 2.900(2) 1.899(2) 173.1(2) 0.17 2.53 G4 THF 27.80
N(3)–H(3N)⋅⋅⋅O(29T)b 2.883(3) 1.922(2) 158.8(1) 0.16 2.39 G2 OTf 25.60
N(4)–H(4N)⋅⋅⋅O(30T)c 2.860(3) 1.859(3) 172.4(2) 0.18 2.65 G3 OTf 29.98
N(5)–H(5N)⋅⋅⋅O(36F) 3.019(2) 2.054(2) 160.1(2) 0.11 1.81 G7 THF 16.12
N(6)–H(6N)⋅⋅⋅O(32T)d 2.951(3) 1.958(3) 168.7(2) 0.14 2.11 G3 OTf 21.39
O(3W)–H(1W)⋅⋅⋅O(38W) 2.781(3) 1.821(3) 175.7(2) 0.20 2.79 G9 H2O 34.06
O(3W)–H(2W)⋅⋅⋅O(34F) 2.703(3) 1.756(2) 167.9(2) 0.23 3.24 G5 THF 49.66
O(5W)–H(3W)⋅⋅⋅O(35F) 2.742(3) 1.815(3) 161.0(2) 0.20 2.90 G6 THF 34.56
O(5W)–H(4W)⋅⋅⋅O(39W) 2.740(3) 1.787(3) 170.4(2) 0.21 3.03 G10 H2O 36.96
O(38W)–H(38W)⋅⋅⋅O(26) 2.830(2) 2.06(2) 141 0.12 1.65 G1 OTf 16.62
O(38W)–H(39W)⋅⋅⋅O(31T) 2.981(3) 2.06(2) 1567 0.12 1.61 G3 OTf 16.44
O(39W)–H(40W)⋅⋅⋅O(28T) 2.875(3) 1.93(2) 171 0.16 2.11 G2 OTf 24.33
O(39W)–H(41W)⋅⋅⋅O(24) 2.880(3) 2.02(2) 148 0.14 1.77 G1 OTf 19.84

  1. Symmetry code: ax, 1 + y, z. b−1 + x, y, z. cx, −1 + y, z. d1 + x, y, z. eEHB calculated after Abramov [15].

Hydrogen bonding can be made visible at the sites in question by mapping the aspherical electron density onto the Hirshfeld surfaces [17, 18]. An impression is given in Figure 3, which shows the Group 1 Hirshfeld surface. Since the HB directions are evenly distributed over the entire surface, it was only possible to display three of the N–H HBs and the O(5W)–H(4W)⋅⋅⋅O(39W) HB in Figure 3. The ED concentration in the latter HB is stronger than in the N–H region, in line with a higher critical point ED density and the larger HB energy on this O–H⋅⋅⋅O HB, see Table 1.

Figure 3: Hirshfeld surface of Group 1, site of the HB O(5W)–H(4W)⋅⋅⋅O(39W) encircled (representation with Moliso [19]).
Figure 3:

Hirshfeld surface of Group 1, site of the HB O(5W)–H(4W)⋅⋅⋅O(39W) encircled (representation with Moliso [19]).

At the atomic level, biological activity is often related to intermolecular interactions. As discussed above the Ca complex under consideration offers a large number of potential intermolecular HB interactions, which do neither exist in the K complex nor in in the un-complexed valinomycin molecule. In total, the Hirshfeld surface shown in part in Figure 3 serves to illustrate sites and strengths of ED concentrations where intermolecular interactions can be established.

A selection of bond critical points (BCP’s, defined by the property that the gradient ∇ρ(r) vanishes at this point [16]) on the covalent bonds and on the Ca···O bonds in the coordination sphere, are given in Table 2. For a summary of all BCP properties on the covalent bonds see the Electronic Supporting Information, Table S1. Low electron density values and positive Laplacians on the BCPs clearly indicate ionic Ca···O contacts. The S–C bonds are normal covalent single bonds [20, 21]. For the S–O bonds of the sulfonate-SO3− group we find a quite large ρ(rBCP) value of 2.15(2) and also a positive Laplacian, so that an ionic contribution can be assumed. Partly covalent and ionic properties were identified in a detailed topological analysis of the S–O bond in the SO2 molecule and in a sulfonyl compound (O2–S–R2) [21]. Bond topological properties on the C–F bonds are as expected and need no further comments [22, 23]. An illustration of the different bond types in terms of the Laplacian distribution along the bonds in question is given in Figure 4. For the N–C and C=O bonds we refer to a comparison of averages reported for BCP properties of amino acids and oligopeptides [24, 25]. We note a small but significant difference in BCP properties on C=O bonds whether they are (O–) C=O or (N–) C=O.

Table 2:

Selection of averaged bond topological properties, details see Table S1 of the ESI.

Bond Length (Å) ρ(rBCP) (e Å–3) ∇2ρ(rBCP) (e Å–5) ε a N b
Ca–O 2.320(31) 0.21(2) 4.9(4) 0.00(−) 12
S–O 1.437(7) 2.15(2) 8.0(15) 0.03(1) 12
S–C 1.825(4) 1.34(1) −7.7(1) 0.0 4
C–F 1.324(4) 2.08(1) −26.3(3) 0.13(1) 12
N–Cα 1.456(5) 1.82(1) −11.1(4) 0.06(1) 6
N–C(=O) 1.333(3) 2.32(1) −23.9(5) 0.24(1) 6
(O–)C=Oc 1.203(2) 3.0(1) −33.9(2) 0.10(−) 6
(N–)C=Od 1.235(3) 2.86(1) −33.0(3) 0.09(−) 6

  1. aThe ellipticity ε is defined by (λ1/λ2) – 1 with λ1 and λ2 being the two principal negative curvatures of ρ(r) at a BCP and is a measure for the asphericity and hence the double bond character of a bond. bN = number of entries contributing to the average. cValin residue. dLac/HyV residue.

Figure 4: Laplacian distribution along bonds of the types Ca–O, S–O, S–C and C–F.
Figure 4:

Laplacian distribution along bonds of the types Ca–O, S–O, S–C and C–F.

Atomic properties were calculated by integration over the atomic basins bound by zero flux surfaces of the gradient vector field ∇ρ(r), which subdivide a structure into transferable substructures [16]. The algorithm introduced by Volkov et al. [26] as implemented in the XDProp subprogram of XD [14] was used. Atomic charges and volumes in the core region are given in Figure 5, detailed lists are provided in the Electronic Supporting Information, Table S2.

Figure 5: Atomic charges (e) and volumes Vtot (Å3) for the atoms in the core region of Group 1, values with positive/negative charges in blue/red.
Figure 5:

Atomic charges (e) and volumes Vtot (Å3) for the atoms in the core region of Group 1, values with positive/negative charges in blue/red.

The strongest positive charge centers are at the calcium and the sulphur sites. Atomic charges of all oxygen atoms are negative, the atoms not part of the triflate fragment have charges around −0.9 e, the oxygen atoms of the triflate SO3 groups are strongly negative. The atomic properties of the triflate Groups 3 and 4 (see Figure S2 in the Electronic Supporting Information) are the same as the ones in the core region of Group 1, so that there is no influence from the neighboring calcium cations. Atomic properties of the fluorine atoms in the CF3 group agree with the earlier finding in that fluorine has almost constant charges and volumes around −0.7 e and ∼18 Å3 [23]. In the CF3 groups the charges of the carbon atoms (∼1.5–1.6 e) and their relatively small atomic volumes are characteristic for this functional group where carbon loses volume which is taken up by the electronegative fluorine atoms [22, 27].

From the summation over atomic properties, group volumes and charges were calculated, see Table 3. The charges of Group 1 on the one hand and Groups 2 and 3 on the other add up to zero, while the other group charges are insignificant. The volume of Group 1 amounts to ∼68% of the unit cell volume (Table 3).

Table 3:

Group properties from summation of atomic properties (charges q and volumes Vtot).

Group q (e) Vtot (Å3) N a
Group 1 2.353 1805.85 192
Group 2 OTF −1.066 118.44 8
Group 3 OTF −1.068 116.11 8
Group 4 THF 0.023 107.99 13
Gropp 5 THF −0.023 107.24 13
Group 6 THF −0.013 109.41 13
Group 7 THF 0.006 108.52 13
Group 8 THFb – – –
Group 9 H2O −0.007 25.12 3
Group 10 H2O 0.000 28.67 3

  1. aN = number of entries contributing to the summation. bAffected by disorder.

The electrostatic potential (ESP) surfaces shown in Figures 6–9 were calculated by using the method of Volkov et al. [28] with the XDProp subprogram of XD2006 [14] and were color coded onto the 0.067 e Å−3 (=0.01 a.u.) ED isosurfaces. The three-dimensional distribution of the ESP is very helpful for the consideration of the reactivity of a chemical system. Negative regions can be regarded as nucleophilic centers; regions with positive ESP are potential electrophilic sites. Figure 6 (left) shows the ESP of the valinomycin molecule of the dinuclear calcium complex. A strong polarization of the ESP is visible in that the exterior region is mostly positive caused by outward directed methyl, ethyl and HB donor N–H groups, while a negative interior is seen, due to the fact that most of the carboxylate oxygen atoms are pointing inwards. In Figure 6 (right) the ESP of the core region is displayed. Its surface is mostly positive, fits into and complements the negative cavity of the valinomycin envelope. When the ESP of the complete Group 1 complex is calculated, the ESP surfaces are significantly different, see Figure 7. The surface is now completely positive, due to the positive charge of this group, with the Ca ions being most strongly positive. The two triflate anions embedded in Group1 cause the least positive regions, with their ESPs distributed between the two Ca ions. Only one triflate ESP is visible in Figure 7, the second one is hidden behind the viewing plane. In Figure 8 Groups 2–10 were additionally included in the calculation, so that the ESP of the complete asymmetric unit of the structure is shown. Now a balance is seen between positive and negative ESPs. A pronounced negative region is caused by the triflate Groups 2 and 3, and only Group 2 is visible in Figure 8, Group 3 behind the viewing plane. The strong positive ESPs at the Ca centers dominates the surrounding, so that the triflate region bridging the Ca cations shows likewise a low positive ESP. This does not hold for the Group 2 and 3 triflate anions, they are the most negative regions seen in Figure 8. In Figure 9 Group 1 is omitted from the ESP calculation, and only Groups 2–10 were included. This representation shows the non-Group 1 ESPs. All THF molecules have a potential gradient from the positive CH2 groups to negative potentials at the oxygen atoms. Figure 9 shows more clearly than in Figures 7 and 8 that the Group 2–10 contributions are arranged on both sides of the Group 1 complex, establishing an environment like a sandwich.

Figure 6: Left: Electrostatic potential for the valinomycin molecule in the dinuclear calcium complex, right: electrostatic potential for the core region of the complex (representations with Moliso [19]).
Figure 6:

Left: Electrostatic potential for the valinomycin molecule in the dinuclear calcium complex, right: electrostatic potential for the core region of the complex (representations with Moliso [19]).

Figure 7: ESP of the Group 1 complex only (representation generated with Moliso [19]).
Figure 7:

ESP of the Group 1 complex only (representation generated with Moliso [19]).

Figure 8: Electrostatic potential of the entire structure, Groups 1–10 (representation with Moliso [19]).
Figure 8:

Electrostatic potential of the entire structure, Groups 1–10 (representation with Moliso [19]).

Figure 9: Electrostatic potential, with Group1 excluded (representation with Moliso [19]).
Figure 9:

Electrostatic potential, with Group1 excluded (representation with Moliso [19]).

3 Conclusions

As the case of valinomycin shows, invariom refinement permits, unlike classical charge density studies, to use conventional resolution diffraction data. It can be applied to large systems, allows to consider disorder and provides an electron density model for valinomycin acting as a ligand in a complex. This model was further analysed to give bond topological/atomic properties, and the ESP. This analysis yields information on covalent (in the valinomycin ligands and in parts of the anions), ionic (Ca–O bonds), partly covalent and ionic bonds (in the sulfonate group). The electron density in hydrogen bond interactions was then mapped onto the Hirshfeld surface. Sites of electron density concentrations were found to spread evenly over the Group 1 surface for the N–H HBs. No regions of preferred HB interaction were identified. From the invariom electron density the ESP was calculated for different subgroups of the structure. The series of ESPs displayed in Figures 6–9 shows a mutual influence of the contributing fragments. Figure 6 illustrates electrostatic complementarity, which facilitates the arrangement of the core region in the valinomycin cavity. The Group 1 complex, a combination of valinomycin and two counterions, shows a predominantly positive ESP caused by the strongly electropositive Ca ions (Figure 7). In the ESP of the entire structure, a localized, sharply negative region is due to the triflate anions, which does not seem to affect the ESP of the Group 1 complex. Joining information from ESP (to indicate nucleophilic/electrophilic sites and highlight ED polarizations) and from Hirshfeld surfaces (to identify sites and strengths of preferred interactions) provides tools to study biological interactions on the level of the electron density. At this level, intermolecular recognition in biological processes takes place via molecular surfaces, which can be better characterized this way, using properties ultimately computed from invariom database fragments.

4 Least-squares refinement of the valinomycin complex B with aspherical scattering factors

The crystals of this compound were initially reported to be free of disorder. However, we found un-modelled electron density at the Group eight THF molecule, and modelled a second disorder conformation for one of its CH2 groups. Shelxle [29] in combination with Shelxl [30] was used to re-visit the ‘spherical’ or independent atom model (IAM) refinement, which entailed to model the disorder using the 3D residual electron density map, and validation of the hydrogen atom sites and bond distances.

The known atomic parameters from the IAM were taken to establish the starting parameters for the subsequent aspherical-atom refinement. For invariom refinement, the data set reported earlier [3, 7] was used. Despite the high Z′ number and the larger number of atoms in the asymmetric unit of the unitt cell, diffraction data allowed satisfactory IAM refinement, leading to an R(F) of 4.82% using Shelxl which was further improved to R(F) of 4.34% by using aspherical scattering factors of the invariom database [9].

The software Invariomtool [31] was used to set up XD system files and to generate constraints. It automatically selects and assigns the corresponding invarioms after analysing the identity and chemical neighbourhood of each atom. Scattering factors up to the hexadecapolar level from the invariom library, including κ parameters, were assigned to all atoms. Library entries were generated with the B3LYP functional and the D95++(3df,3pd) basis set. For the Ca2+ ion, full charge transfer and spherical symmetry were assumed. Likewise, all triflate anions were modelled assuming full charge transfer. Bond distances to hydrogen atoms were elongated to values from energy-minimized structures of the respective model compounds used in scattering factor assignment. Hydrogen positions were initially idealized with the AFIX command in Shelxl. Subsequent riding model constraints for the XDLSM program of the XD2006 program suite [14] from Invariomtool ensured that their relative, elongated positions were maintained. Refinement of positional and displacement parameters (anisotropic for non-hydrogen atoms, isotropic for hydrogen atoms) was carried out until convergence was achieved. In the refinements, the quantity Σw(h) (|Fo(h)|2 − |Fc(h)|2)2 was minimized using the statistical weight w(h) = 1/(σ 2 (Fo(h)2)). Only structure factors which met the criterion Fo2 ≥ 2 σ(Fo2) were included in the refinement. Selected crystallographic data and figures of merit are summarized in Table 4. Tables of atomic coordinates, isotropic and anisotropic displacement parameters are presented in the Electronic Supporting Information, Table S3.

Table 4:

Choice of crystallographic and invariom refinement dataa.

Compound Valinomycin complex (B)
Formula C78H138Ca2F12N6O39S4
Mr, g mol−1 2220.34
Space group (No.) Triclinic P1 (1)
Z 1
V, Å3 2657.1(4)
T, K 110(2)
(Sin θ/λ)max, Å−1 0.725
No. of reflections 31154
Observed reflections [Fo2 ≥ 2 σ(Fo2)] 28703
Invariom refinement
R(F) 0.0434
Rall(F) 0.0471
Rw(F) 0.0508
R(F 2 ) 0.0713
Rall(F 2 ) 0.0721
Rw(F 2 ) 0.1008
Min/max Δρ, e Å−3 −0.27/0.38
Gof 1.165
N ref /N v 20.5

  1. aFor further data see CSD entry YALPIN (1040431) [3] or ref. [7].

5 Supporting information

An additional graphical superposition (Figure S1), bond critical points (Table S1), atomic charges and volumes (Figure S2, Table S2) and atomic coordinates, isotropic and anisotropic displacement parameters and multipole parameters (Table S3). This supplementary material is available online (https://doi.org/10.1515/znb-2022-0067).

Corresponding authors: Peter Luger, Institut für Chemie und Biochemie, Anorganische Chemie, Freie Universität Berlin, Fabeckstraße 36a, D-14195 Berlin, Germany, E-mail: ; and Birger Dittrich, Mathematisch Naturwissenschaftliche Fakultät, Universität Zürich, Winterthurerstraße 190, CH-8057 Zürich, Switzerland, E-mail:

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

1. Fong, C. W. Int. J. Comput. Biol. Drug Des. 2016, 9, 228–246.10.1504/IJCBDD.2016.078284Search in Google Scholar

2. Wu, C. Y., Jan, J. T., Ma, S. H., Kuo, C. J., Juan, H. F., Cheng, Y. S. E., Hsu, H. H., Huang, H. C., Wu, D., Brik, A., Liang, F. S., Liu, R. S., Fang, J. M., Chen, S. T., Liang, P. H., Wong, C. H. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 10012–10017; https://doi.org/10.1073/pnas.0403596101.Search in Google Scholar

3. Groom, C. R., Bruno, I. J., Lightfood, M. P., Ward, S. C. Acta Crystallogr. 2016, B72, 171–179.10.1107/S2052520616003954Search in Google Scholar

4. Pinkerton, M., Steinrauf, L. K., Dawkins, P. Biochem. Biophys. Res. Commun. 1969, 35, 512–518; https://doi.org/10.1016/0006-291x(69)90376-3.Search in Google Scholar

5. Karle, I. L. J. Am. Chem. Soc. 1975, 97, 4379–4386; https://doi.org/10.1021/ja00848a041.Search in Google Scholar PubMed

6. Smith, G. D., Duax, W. L., Langs, D. A., DeTitta, G. T., Edmonds, J. W., Rohrer, D. C., Weeks, C. M. J. Am. Chem. Soc. 1975, 97, 7242–7247; https://doi.org/10.1021/ja00858a008.Search in Google Scholar PubMed

7. Contractor, A. A., Kazerouni, A. M., Michmerhuizen, A. R., Falkenberry, M. L., Segovia, R., Blair, N. M., Kim, S. E., Vander Griend, D. A., Bacsa, J., Khan, F. A., Fujita, M. Supramol. Chem. 2016, 29, 129–138; https://doi.org/10.1080/10610278.2016.1186276.Search in Google Scholar

8. Dittrich, B., Koritsanszky, T., Luger, P. Angew. Chem. Int. Ed. 2004, 43, 2718–2721; https://doi.org/10.1002/anie.200353596.Search in Google Scholar PubMed

9. Dittrich, B., Hübschle, C. B., Pröpper, K., Dietrich, F., Stolper, T., Holstein, J. J. Acta Crystallogr. 2013, B69, 91–104; https://doi.org/10.1107/s0108768113002280.Search in Google Scholar

10. Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J., Wood, P. A. J. Appl. Crystallogr. 2008, 41, 466–470; https://doi.org/10.1107/s0021889807067908.Search in Google Scholar

11. Keller, E., Pierrard, J. S. Schakal99; Albert-Ludwigs University of Freiburg: Freiburg (Germany), 1999.Search in Google Scholar

12. Neupert-Laves, K., Dobler, M. Helv. Chim. Acta 1975, 58, 432–442; https://doi.org/10.1002/hlca.19750580212.Search in Google Scholar PubMed

13. Spek, A. L. Acta Crystallogr. 2009, D65, 148–155; https://doi.org/10.1107/s090744490804362x.Search in Google Scholar

14. Volkov, A., Macchi, P., Farrugia, L. J., Gatti, C., Mallinson, P. R., Richter, T., Koritsánszky, T. XD2006 – A Computer Program for Multipole Refinement, QTAIM Analysis of Charge Densities and Evaluation of Intermolecular Energies from Experimental and Theoretical Structure Factors, University of Buffalo: Buffalo, NY (USA); University of Milano: Milano (Italy); University of Glasgow: Glasgow, Scotland (U.K.); CNRISTM: Milano (Italy); Middle Tennessee State University: Murfreesboro, TN (USA), 2006.Search in Google Scholar

15. Abramov, Y. A. Acta Crystallogr. 1997, A53, 264–272; https://doi.org/10.1107/s010876739601495x.Search in Google Scholar

16. Bader, R. F. W. Atoms in Molecules – A Quantum Theory; Clarendon Press: Oxford, 1994.Search in Google Scholar

17. McKinnon, J. J., Mitchell, A. S., Spackman, M. A. Chem. Eur J. 1998, 4, 2136–2141; https://doi.org/10.1002/(sici)1521-3765(19981102)4:11<2136::aid-chem2136>3.0.co;2-g.10.1002/(SICI)1521-3765(19981102)4:11<2136::AID-CHEM2136>3.0.CO;2-GSearch in Google Scholar

18. Spackman, M. A., McKinnon, J. J., Jayatilaka, D. CrystEngComm 2008, 10, 377–388.Search in Google Scholar

19. Hübschle, C. B., Luger, P. J. Appl. Crystallogr. 2006, 39, 901–904; https://doi.org/10.1107/s0021889806041859.Search in Google Scholar

20. Dittrich, B., Luger, P. Z. Naturforsch. 2017, 72b, 1–10, https://doi.org/10.1515/znb-2016-0178.Search in Google Scholar

21. Grabowsky, S., Luger, P., Buschmann, J., Schneider, T., Schirmeister, T., Sobolev, A. N., Jayatilaka, D. Angew. Chem. Int. Ed. 2012, 51, 6776–6779; https://doi.org/10.1002/anie.201200745.Search in Google Scholar

22. Lentz, D., Patzschke, M., Bach, A., Scheins, St., Luger, P. Org. Biomol. Chem. 2003, 1, 409–414; https://doi.org/10.1039/b208704a.Search in Google Scholar

23. Kalinowski, R., Weber, M., Troyanov, S. I., Paulmann, C., Luger, P. Z. Naturforsch. 2010, 65b, 1–7; https://doi.org/10.1515/znb-2010-0101.Search in Google Scholar

24. Kalinowski, R., Dittrich, B., Hübschle, Ch. B., Paulmann, C., Luger, P. Acta Crystallogr. 2007, B63, 753–767; https://doi.org/10.1107/s0108768107030388.Search in Google Scholar

25. Grabowski, S., Kalinowski, R., Weber, M., Förster, D., Paulmann, C., Luger, P. Acta Crystallogr. 2009, B65, 488–501.10.1107/S0108768109016966Search in Google Scholar

26. Volkov, A., Gatti, C., Abramov, Y., Coppens, P. Acta Crystallogr. 2000, A56, 252–258; https://doi.org/10.1107/s0108767300001628.Search in Google Scholar PubMed

27. Checinska, L., Troyanov, S. I., Mebs, St., Hübschle, Ch. B., Luger, P. Chem. Commun. 2007, 4003–4005; https://doi.org/10.1039/b712694h.Search in Google Scholar PubMed

28. Volkov, A., King, H. F., Coppens, P., Farrugia, L. J. Acta Crystallogr. 2006, A62, 400–408; https://doi.org/10.1107/s0108767306026298.Search in Google Scholar

29. Hübschle, C. B., Sheldrick, G. M., Dittrich, B. J. Appl. Crystallogr. 2011, 44, 1281–1284; https://doi.org/10.1107/s0021889811043202.Search in Google Scholar

30. Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112–123; https://doi.org/10.1107/s0108767307043930.Search in Google Scholar PubMed

31. Hübschle, C. B., Luger, P., Dittrich, B. J. Appl. Crystallogr. 2007, 40, 623–627; https://doi.org/10.1107/s0021889807016524.Search in Google Scholar

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/znb-2022-0067).

Received: 2022-04-19
Accepted: 2022-05-31
Published Online: 2022-08-11
Published in Print: 2022-09-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. In this issue
  3. Research Articles
  4. Crystal structures of sildenafil compounds with nitrate and di(citrato)zinc counterions
  5. Synthesis, crystal structure, and properties of three lead(II) complexes based on the 1,10-phenanthroline ligand
  6. A highly selective and sensitive fluorescent sensor based on a 1,8-naphthalimide with a Schiff base function for Hg2+ in aqueous media
  7. Co-crystallization of dimethyl N-cyanodithioiminocarbonate and bis[(aqua)-µ2-hydroxy-n-butyldichlorotin(IV)]
  8. Synthesis of ring-A serjanic acid derivatives and their cytotoxic evaluation through the brine shrimp lethality assay (BSLA)
  9. Electron density of the 1:2 complex of valinomycin with calcium triflate observed in crystals of the composition (valinomycin)Ca2(OTf)4(THF)5(H2O)4
  10. Two zinc and cadmium coordination polymers constructed with bis(4-(1H-imidazol-1-yl)phenyl)methanone and naphthalene-1,4-dicarboxylate ligands: synthesis and structural characterization
  11. Characterization of hydrophilic carbon nanohorns prepared by the arc-in-water method
  12. Crystal structure determination and characterization of Sm3SiO5F3
  13. A four-fold three-dimensional zinc(II) coordination polymer based on 4,4′-bis(2-methyl-imidazolyl)biphenyl and 5-sulfoisophthalate ligands: synthesis, structure and properties
  14. Synthesis, structures, and photophysical properties of two Cu(I) complexes supported by N-heterocyclic carbene and phosphine ligands
  15. Synthesis of chiral binaphthol-based bishydroxylamines
https://doi.org/10.1515/znb-2022-0067
Keywords for this article
electron density; invariom formalism; macrolide antibiotic; valinomycin

Articles in the same Issue

  1. Frontmatter
  2. In this issue
  3. Research Articles
  4. Crystal structures of sildenafil compounds with nitrate and di(citrato)zinc counterions
  5. Synthesis, crystal structure, and properties of three lead(II) complexes based on the 1,10-phenanthroline ligand
  6. A highly selective and sensitive fluorescent sensor based on a 1,8-naphthalimide with a Schiff base function for Hg2+ in aqueous media
  7. Co-crystallization of dimethyl N-cyanodithioiminocarbonate and bis[(aqua)-µ2-hydroxy-n-butyldichlorotin(IV)]
  8. Synthesis of ring-A serjanic acid derivatives and their cytotoxic evaluation through the brine shrimp lethality assay (BSLA)
  9. Electron density of the 1:2 complex of valinomycin with calcium triflate observed in crystals of the composition (valinomycin)Ca2(OTf)4(THF)5(H2O)4
  10. Two zinc and cadmium coordination polymers constructed with bis(4-(1H-imidazol-1-yl)phenyl)methanone and naphthalene-1,4-dicarboxylate ligands: synthesis and structural characterization
  11. Characterization of hydrophilic carbon nanohorns prepared by the arc-in-water method
  12. Crystal structure determination and characterization of Sm3SiO5F3
  13. A four-fold three-dimensional zinc(II) coordination polymer based on 4,4′-bis(2-methyl-imidazolyl)biphenyl and 5-sulfoisophthalate ligands: synthesis, structure and properties
  14. Synthesis, structures, and photophysical properties of two Cu(I) complexes supported by N-heterocyclic carbene and phosphine ligands
  15. Synthesis of chiral binaphthol-based bishydroxylamines
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