Pi-pi Contacts Research Articles

The Energetic Origins of Pi-Pi Contacts in Proteins.

Accurate potential energy models of proteins must describe the many different types of noncovalent interactions that contribute to a protein's stability and structure. Pi-pi contacts are ubiquitous structural motifs in all proteins, occurring between aromatic and nonaromatic residues and play a nontrivial role in protein folding and in the formation of biomolecular condensates. Guided by a geometric criterion for isolating pi-pi contacts from classical molecular dynamics simulations of proteins, we use quantum mechanical energy decomposition analysis to determine the molecular interactions that stabilize different pi-pi contact motifs. We find that neutral pi-pi interactions in proteins are dominated by Pauli repulsion and London dispersion rather than repulsive quadrupole electrostatics, which is central to the textbook Hunter-Sanders model. This results in a notable lack of variability in the interaction profiles of neutral pi-pi contacts even with extreme changes in the dielectric medium, explaining the prevalence of pi-stacked arrangements in and between proteins. We also find interactions involving pi-containing anions and cations to be extremely malleable, interacting like neutral pi-pi contacts in polar media and like typical ion-pi interactions in nonpolar environments. Like-charged pairs such as arginine-arginine contacts are particularly sensitive to the polarity of their immediate surroundings and exhibit canonical pi-pi stacking behavior only if the interaction is mediated by environmental effects, such as aqueous solvation.

Design of robust malate dehydrogenases by assembly of motifs of halophilic and thermophilic enzyme based on interaction network

Robust oxidoreductases in non-aqueous system is promising to bridge the gap between research and industrial application. Malate dehydrogenases (MDHs) were select as model enzyme for redesign based on motif assembly study. The approach involved first selecting or building a stable framework, which subsequently served as a template for replace of functional motifs. First, for scaffold selection, dynamic conformational change of halophilic and thermophilic MDHs was studied by molecular dynamic simulations with increasing salt concentration. Second, computationally inserted the robust motifs which responded to salt concentration into the selected scaffold, and resulted novel MDHs. Third, the top-scoring designs of structure compatibility and dynamic harmony evaluation were selected for experimental verification. The experimental result indicated that the designed MDH03 had the enhanced thermostability, pH and ionic liquid tolerance. The activity of MDH03 was 1.38-fold of parent enzyme in reaction system contain [EMIM]BF4. Further study of amino acid residues interaction network explained the reason of robustness of MDH03 based on high-density salt bridges. Research also indicated that the hydrophobic contacts and pi-pi contacts of interfacial interactions of motifs play a key role for activity and stability of MDH03. This work promoted an approach to design robust dehydrogenase with high ionic liquids tolerance and promote the further application in biosensors.

Nuclear immunophilin FKBP39 from Drosophila melanogaster drives spontaneous liquid-liquid phase separation

The FKBP39 from Drosophila melanogaster is a multifunctional regulatory immunophilin. It contains two globular domains linked by a highly charged disordered region. The N-terminal domain shows homology to the nucleoplasmin core domain, and the C-terminal domain is characteristic for the family of the FKBP immunophilin ligand binding domain. The specific partially disordered structure of the protein inspired us to investigate whether FKBP39 can drive spontaneous liquid-liquid phase separation (LLPS). Preliminary analyses using CatGranule and Pi-Pi contact predictors suggested a propensity for LLPS. Microscopy observations revealed that FKBP39 can self-concentrate to form liquid condensates. We also found that FKBP39 can lead to LLPS in the presence of RNA and peptides containing Arg-rich linear motifs derived from selected nuclear and nucleolar proteins. These heterotypic interactions have a stronger propensity for driving LLPS when compared to the interactions mediated by self-associating FKBP39 molecules. To investigate whether FKBP39 can drive LLPS in the cellular environment, we analysed it in fusion with YFP in COS-7 cells. The specific distribution and diffusion kinetics of FKBP39 examined by FRAP experiments provided evidence that immunophilin is an important driver of phase separation. The ability of FKBP39 to go into heterotypic interaction may be fundamental for ribosome subunits assembly.

Role of Proinsulin Self-Association in Mutant INS Gene-Induced Diabetes of Youth.

Abnormal interactions between misfolded mutant and wild-type (WT) proinsulin (PI) in the endoplasmic reticulum (ER) drive the molecular pathogenesis of mutant INS gene-induced diabetes of youth (MIDY). How these abnormal interactions are initiated remains unknown. Normally, PI-WT dimerizes in the ER. Here, we suggest that the normal PI-PI contact surface, involving the B-chain, contributes to dominant-negative effects of misfolded MIDY mutants. Specifically, we find that PI B-chain tyrosine-16 (Tyr-B16), which is a key residue in normal PI dimerization, helps confer dominant-negative behavior of MIDY mutant PI-C(A7)Y. Substitutions of Tyr-B16 with either Ala, Asp, or Pro in PI-C(A7)Y decrease the abnormal interactions between the MIDY mutant and PI-WT, rescuing PI-WT export, limiting ER stress, and increasing insulin production in β-cells and human islets. This study reveals the first evidence indicating that noncovalent PI-PI contact initiates dominant-negative behavior of misfolded PI, pointing to a novel therapeutic target to enhance PI-WT export and increase insulin production.

Pi-Pi contacts are an overlooked protein feature relevant to phase separation.

Protein phase separation is implicated in formation of membraneless organelles, signaling puncta and the nuclear pore. Multivalent interactions of modular binding domains and their target motifs can drive phase separation. However, forces promoting the more common phase separation of intrinsically disordered regions are less understood, with suggested roles for multivalent cation-pi, pi-pi, and charge interactions and the hydrophobic effect. Known phase-separating proteins are enriched in pi-orbital containing residues and thus we analyzed pi-interactions in folded proteins. We found that pi-pi interactions involving non-aromatic groups are widespread, underestimated by force-fields used in structure calculations and correlated with solvation and lack of regular secondary structure, properties associated with disordered regions. We present a phase separation predictive algorithm based on pi interaction frequency, highlighting proteins involved in biomaterials and RNA processing.

Cyanide-Bridged Fe(III)−Mn(III) Bimetallic Systems Assembled from the fac-Fe Tricyanide and Mn Schiff bases: Structures, Magnetic Properties, and Density Functional Theory Calculations

Reaction of [(Tp)Fe(CN)(3)](-) [Tp = hydrotris(pyrazolyl)borate] with respective Mn(III) Schiff bases led to the formation of four dimeric molecules, [(Tp)Fe(CN)(3)][Mn(1-napen)(H(2)O)].MeCN.4H(2)O [1; 1-napen = N,N'-ethylenebis(2-hydroxy-1-naphthylideneiminato) dianion], [(Tp)Fe(CN)(3)][Mn(5-Clsalen)(H(2)O)] [2; 5-Clsalcy = N,N'-(trans-1,2-cyclohexanediylethylene)bis(5-chlorosalicylideneiminato) dianion], [(Tp)Fe(CN)(3)][Mn(2-acnapen)(MeOH)].MeOH [3; 2-acnapen = N,N'-ethylenebis(1-hydroxy-2-acetonaphthylideneiminato) dianion], [(Tp)Fe(CN)(3)][Mn(3-MeOsalen)(H(2)O)] [4; 3-MeOsalen = N,N'-ethylenebis(3-methoxysalicylideneiminato) dianion], and a one-dimensional (1D) zigzag chain [(Tp)Fe(CN)(3)][Mn(2-acnapen)].H(2)O (5). The dimers contain multiple intermolecular interactions such as hydrogen bonds, face-to-face pi-pi contacts, and edge-to-face CH-pi forces, raising molecular dimensions from one-dimensional (1D) up to three-dimensional (3D) arrays, whereas there are no pi-pi stacking interactions in the 1D chain compound. Magnetic measurements reveal that ferromagnetic couplings are obviously operative between Mn(III) and Fe(III) spin centers transmitted by CN bridges for 1-3 and 5, and antiferromagnetic interactions are however unexpectedly present in 4. On the basis of the proper spin Hamiltonians, magnetic exchange couplings are estimated to be in the span from 1.79 to 7.48 cm(-1) for the ferromagnetically coupled systems and -1.40 cm (-1) for the antiferromagnetic dimer. A slow magnetic relaxation is tangible in 5, which is in connection with isolated chains devoid of any intermolecular noncovalent interactions. Density Functional Theory (DFT) calculations and comparison of structural parameters suggest that the observed magnetic behaviors are mainly associated with the bending of the Mn-N[triple bond]C angle in the bridging pathway.

Unraveling the Molecular Recognition of Amino Acid Derivatives by a Pseudopeptidic Macrocycle: ESI-MS, NMR, Fluorescence, and Modeling Studies

The binding between a pseudopeptidic macrocyclic naphthalenophane and different N-protected amino acid derivatives has been thoroughly studied by ESI-MS, NMR, fluorescence, and molecular modeling. Careful NMR titration experiments led to the characterization of the intermolecular noncovalent interactions, reflecting a slight side chain and l-stereoselectivity of the host-guest complexes. The data suggest the formation of an intimate ionic pair after the proton transfer from the carboxylic substrate to the amino macrocycle. Additional intermolecular interactions like H-bonding and pi-pi contacts are also important. This receptor shows a stronger interaction with substrates bearing aromatic rings, either in the side chain or in the N-protecting group. Besides, for N-Z-Phe-OH, a moderate enantioselectivity has been observed. Mass spectrometry suggests the formation of supramolecular complexes with stoichiometries higher than 1:1. The dual nature of the fluorescence emission of the macrocyclic receptor allowed determining binding constants and pertinent thermodynamic parameters. On the basis of the experimental data (NMR titrations, intermolecular ROESY, VT-NMR) and with the help of molecular modeling, a reasonable structure for the supramolecular complexes can be proposed, in which the interactions with the naphthyl ring of the receptor play a fundamental role in the strength and selectivity of the molecular recognition event.

Comparison of halogen bonding and van der Waals and π–π interactions in 4,5-dibromo-2-hexyloxyphenol

The title compound, C(12)H(16)BrO(2), is an interesting case of a simple organic molecule making use of five different types of intra- and intermolecular interactions (viz. conventional and nonconventional hydrogen bonds, and pi-pi, Br...Br and Br...O contacts), all of them relevant in the molecular and crystal structure geometry. The molecules are strictly planar, with an intramolecular O-H...O hydrogen bond, and associate into two-dimensional structures parallel to (201) through two different types of halogen bonding. The planar structures, in turn, stack parallel to each other interlinked by C-H...pi and pi-pi contacts. Also discussed are the relevant structural features leading to the rather low melting point of the compound.

Extended structures containing Pt(ii)–Tl(i) bonds. Effect of these interactions on the luminescence of cyclometalated Pt(ii) compounds

Neutralization reactions of the appropriate precursors (NBu(4))[Pt(bzq)(C[triple bond, length as m-dash]C-R)(2)] and (NBu(4))[Pt(Cinsertion markN)(CN)(2)] (Cinsertion markN = bzq, ppy) with Tl(I) salts afford [{PtTl(bzq)(C[triple bond, length as m-dash]C-R)(2)}(2)] [R = Ph (), C(5)H(4)N-2 ()] and [PtTl(Cinsertion markN)(CN)(2)] [Cinsertion markN = bzq (), ppy ()], respectively. X-Ray diffraction studies of complexes show the existence of Pt(II)-Tl(I) bonds. In .CH(2)Cl(2) the platinum-thallium units are associated in tetranuclear Pt(2)Tl(2) entities which generate a 3-D network through short Tlpi(2-py) and pipi(bzq) contacts and additional weak Cl(2)HC-Hpi(C[triple bond, length as m-dash]C) nonclassical interactions. Compounds and show extended 2-D networks by connection of the organometallic "PtTl(Cinsertion markN)(CN)(2)" units, through secondary TlN[triple bond, length as m-dash]C contacts and moderate pipi(bzq) interactions in the case of . Complexes containing the bzq group exhibit in the solid state "luminescence thermochromism" associated to dual emission. At room temperature they show an intense, visible orange (: lambda(max) 625 nm), orange-red (: lambda(max) 640 nm) or yellow (: lambda(max) 582 nm) luminescence that changes to yellowish-green (: lambda(max) 532 nm) or green [: lambda(max) 524 nm; : lambda(max) 512 nm] upon cooling to 77 K. The unstructured low energy (LE) bands attributed to (3)pi-pi* excimeric emissions due to extensive pi-pi interactions are dominant at room temperature. By contrast, the high energy (HE) bands are highly structured and predominant at 77 K. Due to the presence of Pt-Tl bonds these HE emissions are bathochromically shifted in relation to the precursors' ones and have been tentatively assigned to a metal-metal'-to-ligand (bzq) charge transfer MM'LCT [d/s sigma*(Pt,Tl) -->pi*(Cinsertion markN)] mixed, as in the corresponding precursors, with some intraligand (3)IL[pi(Cinsertion markN') -->pi*(Cinsertion markN)] in and or ligand-to-ligand charge transfer (alkynyl to bzq) (3)LL'CT in complexes and . Complex [PtTl(ppy)(CN)(2)] , which does not show short contacts between the phenylpyridinate groups in solid state, only shows the HE green structured band both at 298 K and at 77 K. Only the cyanide derivatives are soluble and both spectroscopic (NMR and UV-Vis) and emission data (MeOH, 298 K and 77 K) indicate that the Pt(II)-Tl(I) bond breaks down in solution.

Chiral substituent containing perylene monoanhydride monoimide and its highly soluble symmetrical diimide: synthesis, photophysics and electrochemistry from dilute solution to solid state

A new chiral perylene monoanhydride monoimide (1) with a sterically hindered chiral amine was successfully synthesized for further selective functionalization at terminal positions. At the same time, the chiral perylene diimide (2) with the same amine has been synthesized. The synthesized products were characterized using the data from NMR, IR, MS, UV-vis, DSC, TGA, elemental analysis and cyclic and square wave voltammetry. Compound 2 shows an excellent solubility of 200 mg mL(-1) in chloroform. The band gap energy (Eg), LUMO and HOMO energy values were 2.28, -3.77 and -6.05 eV for 2, respectively in chloroform. In solid state, the band gap energy (Eg), LUMO and HOMO energy values were 1.96, -4.22 and -6.18 eV for 1 and 1.92, -4.13 and -6.05 eV for 2, respectively. Whereas 1 (solid state: -0.58 and -0.69 V vs. ferrocene/ferrocenium couple) and 2 (in chloroform: -1.03 and -1.22 V vs. ferrocene/ferrocenium couple) show two reversible reduction steps, 2 exhibits only one reversible wave (solid state: -0.67 V vs. ferrocene/ferrocenium couple). The diffusion coefficients were determined as 1.91 x 10(-7) and 8.47 x 10(-7) cm2 s(-1) for 1 and 2 in solid state, respectively, and 1.27 x 10(-5) cm2 s(-1) for 2 in solution. The solid state emission ability of the chiral products ( is much more emissive than ) remains a challenge for photonic, electronic and sensor applications. 1 and 2 showed high thermal stability. Efficient prevention of intermolecular pi-pi contacts of fluorophores results in an excellent fluorescence emission in solid state and solubility for 2.

Two different modes of halogen bonding in two 4-nitroimidazole derivatives

In the crystal structures of the two imidazole derivatives 5-chloro-1,2-dimethyl-4-nitro-1H-imidazole, C(5)H(6)ClN(3)O(2), (I), and 2-chloro-1-methyl-4-nitro-1H-imidazole, C(4)H(4)ClN(3)O(2), (II), C-Cl...O halogen bonds are the principal specific interactions responsible for the crystal packing. Two different halogen-bond modes are observed: in (I), there is one very short and directional C-Cl...O contact [Cl...O = 2.899 (1) A], while in (II), the C-Cl group approaches two different O atoms from two different molecules, and the contacts are longer [3.285 (2) and 3.498 (2) A] and less directional. In (I), relatively short C-H...O hydrogen bonds provide the secondary interactions for building the crystal structure; in (II), the C-H...O contacts are longer but there is a relatively short pi-pi contact between molecules related by a centre of symmetry. The molecule of (I) is almost planar, the plane of the nitro group making a dihedral angle of 6.97 (7) degrees with the mean plane of the imidazole ring. The molecule of (II) has crystallographically imposed mirror symmetry and the nitro group lies in the mirror plane.

Solid-emissive fluorophores constructed by a non-planar heteropolycyclic structure with bulky substituents: synthesis and X-ray crystal structures

Novel solid-emissive indeno[1,2-b]benzo[4,5-e]pyran-11-one-type fluorophores having non-planar structures with sterically hindered substituents (R = butyl, phenyl, and thienyl) have been designed and conveniently synthesized. The fluorescence quantum yields of in 1,4-dioxane were (Phi = 0.053) >> (Phi = 0.013) > (Phi = 0.003). On the other hand, the solid-state fluorescence quantum yields of the fluorophores were (Phi = 0.39) > (Phi = 0.15) > (Phi = 0.06). To elucidate the large differences in the quantum yields in solution and in the solid state and among the fluorophores , we performed time-resolved fluorescence spectroscopic measurements, semi-empirical molecular orbital calculations (AM1 and INDO/S), and X-ray crystallographic analyses of . The comparison of the values of the radiative and non-radiative rate constants determined by the time-resolved spectroscopic measurements in solution and in the crystalline state supported that non-radiative decay is reduced by restriction of the rotation of the phenyl and thienyl rings in the solid state. In addition, the X-ray crystal structures demonstrated that, in and , the non-planar structure with sterically hindered substituents prevents the fluorophores from forming short pi-pi contacts and produces strong solid-state fluorescence. On the other hand, in the crystal of , the formation of continuous intermolecular CH[dot dot dot]S bonding between neighboring fluorophores was found to increase short pi-pi contacts and reduce the fluorescence intensity.

From an ST = 3 Single-Molecule Magnet to Diamagnetic Ground State Depending on the Molecular Packing of MnIIIsalen-type Dimers Decorated by N,N‘-Dicyano-1,4-naphthoquinonediiminate Radicals

Two manganese(III) tetradentate Schiff-base dimers to which N,N'-dicyano-1,4-naphthoquinonediiminate (DCNNQI) radicals are attached have been selectively synthesized by varying the solvents used in the reactions: [Mn2(5-MeOsaltmen)2(DCNNQI)2].MeOH (1) and [Mn2(5-MeOsaltmen)(2)(DCNNQI)(2)] x 2CH2Cl2.2CH3CN (2) [5-MeOsaltmen2- = N,N'-(1,1,2,2-tetramethylethylene)bis(5-methoxysalicylideneiminate)]. These two complexes share the same molecular core, [(DCNNQI.-)-Mn(III)-(O)2-Mn(III)-(DCNNQI.-)], where -(O)2- is a biphenolate bridge in the out-of-plane dimerized [Mn(2)(5-MeOsaltmen)2]2+ moiety. However, their packing arrangements are completely different. Whereas complex 1 is found to be relatively isolated, strong intermolecular dimerization of the DCNNQI moieties (with the nearest contact being approximately 3.0 A) is observed in 2, forming a one-dimensional chain of [-Mn(III)-(O)2-Mn(III)-(DCNNQI.-)2-](infinity). The magnetic susceptibility of 1 can be modeled with an [S = 1/2, 2, 2, 1/2] four-spin system including strong antiferromagnetic Mn(III)/DCNNQI radical coupling (J(Mn/rad)/kB = -23 K) and ferromagnetic Mn(III)/Mn(III) coupling through the biphenolate bridge (J(Mn/Mn)/kB = +2.0 K). These interactions lead to an ST = 3 ground state that possesses significant uniaxial anisotropy (D(S=3)/kB = -2.1 K). Low-temperature ac and dc magnetic data of 1 reveal its single-molecule magnet behavior with quantum tunneling of the magnetization. By contrast, 2 possesses the diamagnetic ground state induced by dominating Mn(III)-Mn(III) antiferromagnetic interactions mediated by the diamagnetic DCNNQI dimers and/or pi-pi contact along the b axis.

Molecular design of novel non-planar heteropolycyclic fluorophores with bulky substituents: convenient synthesis and solid-state fluorescence characterization

Novel indeno[1,2-b]benzo[4,5-e]pyran-11-one-type fluorophores exhibiting intense solid-state fluorescence were conveniently synthesized and the relation between their solid-state photophysical properties and the X-ray crystal structures were investigated, which demonstrates that non-planar structures with sterical hindered substituents prevent the fluorophores from forming short pi-pi contacts causing fluorescence quenching in the solid state.

(2Z)-3-(5-Hydroxy-4-oxo-4H-chromen-3-yl)acrylonitrile

The title compound, C12H7NO3, consists of a chromone moiety substituted in position 3 with an acrylonitrile group in a Z configuration. The two planar groups are twisted with respect to one another. The only significant hydrogen bond in the structure is an intramolecular O-H...O bond. pi-pi contacts connecting aromatic groups and C-H...O intermolecular weak interactions lead to a supramolecular layer arrangement.

Introduction of a pi-pi interaction at the active site of a cupredoxin: characterization of the Met16Phe Pseudoazurin mutant.

The Met16Phe mutant of the type 1 copper protein pseudoazurin (PACu), in which a phenyl ring is introduced close to the imidazole moiety of the His81 ligand, has been characterized. NMR studies indicate that the introduced phenyl ring is parallel to the imidazole group of His81. The mutation has a subtle effect on the position of the two S(Cys)-->Cu(II) ligand-to-metal charge transfer bands in the visible spectrum of PACu(II) and a more significant influence on their intensities resulting in a A(459)/A(598) ratio of 0.31 for Met16Phe as compared to a A(453)/A(594) ratio of 0.43 for wild-type PACu(II) at pH 8. The electron paramagnetic resonance spectrum of the Met16Phe variant is more axial than that of the wild-type protein, and the resonance Raman spectrum of the mutant exhibits subtle differences. A C(gamma)H proton of Met86 exhibits a much smaller hyperfine shift in the paramagnetic (1)H NMR spectrum of Met16Phe PACu(II) as compared to its position in the wild-type protein, which indicates a weaker axial Cu-S(Met86) interaction in the mutant. The Met16Phe mutation results in an approximately 60 mV increase in the reduction potential of PACu. The pK(a) value of the ligand His81 decreases from 4.9 in wild-type PACu(I) to 4.5 in Met16Phe PACu(I) indicating that the pi-pi contact with Phe16 stabilizes the Cu-N(His81) interaction. The Met16Phe variant of PACu has a self-exchange rate constant at pH 7.6 (25 degrees C) of 9.8 x 10(3) M(-)(1) s(-)(1) as compared to the considerably smaller value of 3.7 x 10(3) M(-)(1) s(-)(1) for the wild-type protein under identical conditions. The enhanced electron transfer reactivity of Met16Phe PACu is a consequence of a lower reorganization energy due to additional active site rigidity caused by the pi-pi interaction between His81 and the introduced phenyl ring.

Five-coordinate iron(III) porphycenes: (1)H NMR, magnetic, and structural studies.

Five-coordinate iron(III) 2,7,12,17-tetrapropylporphycene (TPrPc)Fe(III)X (X = C(6)H(5)O(-), Cl(-), Br(-), I(-), ClO(4)(-)) complexes have been investigated. The (1)H NMR spectra demonstrate downfield shifts for pyrrole resonances [(TPrPc)Fe(III)(C(6)H(5)O), 65.3 ppm; (TPrPc)Fe(III)Cl, 28.5 ppm] but large upfield ones for (TPrPc)Fe(III)Br (-7.8 ppm), (TPrPc)Fe(III)I (-49.4 ppm), and (TPrPc)Fe(III)ClO(4) (-77.1 ppm) (294 K, CD(2)Cl(2)). The pyrrole chemical shifts span the remarkable +70 to -80 ppm range. The variable-temperature (1)H NMR spectra of (TPrPc)Fe(III)X demonstrate anti-Curie behavior with a sign reversal for (TPrPc)Fe(III)Cl. These behaviors are consistent with the admixed S = 3/2, 5/2 ground electronic state with a dominating contribution of the S = 3/2 one. In terms of the chemical shift, (TPrPc)Fe(III)(ClO(4)) can be considered as an example of the purest S = 3/2 state in the investigated series. The extent of the S = 5/2 contribution in the admixed S = 3/2, 5/2 ground electronic state, as gradated solely the basis of the pyrrole proton paramagnetic shifts, is controlled by the strength of the axial ligand, following the magnetochemical series (Evans, D. R.; Reed, C. A. J. Am. Chem. Soc. 2000, 122, 4660). Significantly iron(III) 2,7,12,17-tetrapropylporphycene, soluble in typical organic solvents, can be considered as a universal framework to classify the ligand strength in a magnetochemical series, consistently using the beta-H pyrrole paramagnetic shifts as a fundamental criterion. The structure of (TPrPc)Fe(III)Cl has been determined by X-ray crystallography. The iron is five-coordinate with bonds of nearly equal length to the four pyrrole nitrogen atoms (Fe-N in the range 1.983(5)-2.006(6) A). The iron lies 0.583(1) A out of the mean plane of the macrocycle and 0.502(5) A out of the mean N(4) plane. In the solid, pairs of molecules are positioned about the center of symmetry so there is face-to-face pi-pi contact. The mean plane separation is 3.38 A, and the lateral shift of the porphycene center along the Fe-N bond is 4.490 A. The distance from one porphycene center to the other is 5.62 A, and the iron-iron separation is 6.304(2) A.