Crystal structure data of porphyrins under study,
Abstract
Crystal engineering is an emerging area of research in material, biological, and pharmaceutical chemistry that involves synthesis of new materials, analysis of its structure including intermolecular interactions using X‐ray crystallography as well as computational methods. It has been shown that the intermolecular interactions involving organic fluorine such as C−F∙∙∙H, F∙∙∙F, and C−F∙∙∙π play an important role in stabilizing the supramolecular assemblies, especially in the absence of strong intermolecular forces. Recently, non‐covalent interactions involving conjugated aromatic system such as porphyrins have been studied intensively. The synthetic porphyrins are of widespread attention because of their close resemblance to naturally occurring tetrapyrrolic pigments and they find various materials and biological applications. In this book chapter, we disclose our recent findings on detailed crystal structure analysis of a few series of fluorinated porphyrins using single‐crystal XRD as well as computational Hirshfeld surface analysis to understand the role of close contacts involving fluorine in the molecular crystal packing.
Keywords
- Porphyrinoids
- fluorinated porphyrins
- crystal structure elucidation
- intermolecular interactions
- Hirshfeld surfaces
1. Introduction
Porphyrins are highly conjugated tetrapyrrolic pigments widely found in nature. They play a significant role in biological functions such as electron transfer, oxygen transport, and photosynthetic processes [1]. Most of the naturally occurring macro molecules such as hemoglobin chlorophyll, cytochromes have porphyrin as the basic unit. In these large classes of intensely colored macrocyclic pigments, the four pyrrole subunits are interconnected by methine bridges. The synthesis of porphyrins can be achieved using the synthetic routes namely Rothemund method, Adler‐Longo method, or Lindsey method [2–6]. Synthetic porphyrins are of two types, which include
In recent years, fluorinated porphyrins are shown much attention since the pharmacological properties can be enhanced by the incorporation of fluorine atoms, and they are very effective in bio‐medical applications [12, 13]. The reason behind the fact is that the little atom fluorine is having unique properties such as metabolic stability, binding selectivity, absorption, distribution, and excretion characteristics. Owing to the high electronegativity with its small size makes fluorine an ideal candidate for the replacement of hydrogen. Importantly, by increasing the lipophilicity and also by reducing the charges present in the molecule, fluorinated drugs possess excellent membrane penetration capability compared to its non‐fluorinated counter parts [14]. The fluorinated drugs are numerous, and hence, the study of weak intermolecular interactions involving fluorine is essential in the field of medicinal chemistry to promote the discovery of new drugs of desirable profiles.
Intermolecular interactions are mainly of two categories [15], namely isotropic or directional (C∙∙∙C, C∙∙∙H, H∙∙∙H interactions) that define the size, shape as well as close packing and anisotropic or non‐directional (hydrogen bonds, charge transfer interactions, halogen interaction, and heteroatom interactions). The weak individual intermolecular interactions act co‐operatively and provide a better stability to the crystal packing. The analysis of nature and strength of intermolecular interactions is really important in the area of crystal engineering in order to design new materials especially drugs of desirable properties. They can be studied using X‐ray crystallography as well as computational methods [16]. Interactions involving fluorine are of mainly three kinds, namely C−F∙∙∙H, F∙∙∙F, and C−F∙∙∙π which provides stability to form molecular self‐assemblies especially in the absence of strong intermolecular forces.
Study of weak interactions involving porphyrins offers an interesting field of research in crystal engineering [17]. The energetically weak interactions such as van der Waals forces, hydrogen bonding, or metal coordination are the holding forces to make the self‐assembly of porphyrins and quantifying these non‐covalent interactions often brings a better understanding in these supramolecular self‐assemblies. In this context, Hirshfeld surface (HS) analysis [18] is an important technique that helps to get the detailed information about the crystal structures in terms of intermolecular interactions. HSs and 2D fingerprint plots (FPs) were generated using the single crystal X‐ray diffraction data by Crystal Explorer 3.1 [19]. The term dnorm is a ratio of the distances of any surface point to the nearest interior (di) and exterior (de) atom and the van der Waals radii of the atoms [20]. The red color in the HSs indicates the closest contact bearing a negative value of dnorm with di + de is shorter than the sum of the relevant van der Waals radii. Whereas the white color denotes the intermolecular distances close to van der Waals contacts with dnorm equal to zero. The contacts longer than the sum of van der Waals radii with positive dnorm values are blue in color. The 2D FP (di versus de) recognizes the presence of various non‐covalent interactions present in the molecular crystals [21]. In this book chapter, we wish to discuss our recent observations on the detailed crystal structure analysis of a few series of fluorinated porphyrins (Figure 1) using single crystal X‐ray crystallography. The role of weak intermolecular interactions in the molecular crystal packing was quantitatively analyzed using computational HS analysis by Crystal Explorer 3.1. Also, the role of organic fluorine towards crystal packing is discussed in detail.
2. Synthesis of fluorinated porphyrins
Synthesis of 5,10,15,20‐tetrakis(2′,6′‐difluorophenyl)porphyrin, H2T(2′,6′‐DFP)P,
3. Structural determination of fluorinated porphyrins
The single crystals of the porphyrins were grown at room temperature by vapor diffusion method using appropriate solvents. The X‐ray data were obtained using a Bruker AXS Kappa Apex II CCD diffractometer with graphite monochromated Mo Kα radiation (
3.1. Structural description of MT(2′,6′‐DFP)P (1a−1d)
The porphyrin ligand
There are no direct π−π and intramolecular interactions seen from the geometrical analysis on the crystal structures of porphyrins,
Empirical formula | C44H22F8N4 | C46H28CoF8N4O2 | C44H20CuF8N4 | C46H28ZnF8N4O2 |
Fw | 758.66 | 879.65 | 820.18 | 886.09 |
Color | Purple | Pink | Red | Red |
Crystal system | Monoclinic | Monoclinic | Monoclinic | Monoclinic |
Space group | P21/c | P21/n | P21/c | P21/n |
a, Å | 12.5342(10) | 12.426(5) | 12.5477(7) | 12.4217(18) |
b, Å | 11.4384(9) | 12.723(5) | 11.3955(6) | 12.529(2) |
c, Å | 12.1720(10) | 12.709(5) | 12.1642(7) | 12.6954(18) |
α, (°) | 90.0 | 90.000(5) | 90.0 | 90.0 |
β, (°) | 97.080(3) | 114.615(5) | 96.391 | 114.092(17) |
γ, (°) | 90.0 | 90.000(5) | 90.0 | 90.0 |
vol (Å3) | 1731.8(2) | 1826.7(13) | 1728.52(17) | 1803.7(5) |
Z | 2 | 2 | 2 | 2 |
Dcalcd (mg/m3) | 1.455 | 1.599 | 1.576 | 1.632 |
Wavelength (), Å | 0.71073 | 0.71073 | 0.71073 | 0.71073 |
T (K) | 293(2) | 293(2) | 293(2) | 293(2) |
No. of unique reflections | 2690 | 3583 | 5329 | 3165 |
No. of parameters refined | 258 | 278 | 259 | 351 |
GOF on F2 | 1.026 | 1.055 | 1.013 | 1.059 |
R1a | 0.0359 | 0.0488 | 0.0372 | 0.0766 |
wR2b | 0.0818 | 0.1445 | 0.0944 | 0.1685 |
In order to quantify the various intermolecular interactions, HSs and their associated finger print plots were calculated using
From the FP plots, the division of contributions is possible for different interactions including C∙∙∙H, F∙∙∙H/C/F, H∙∙∙H, and N∙∙∙H through interactive computer graphics which commonly overlap in the full FP plots. The shapes of FP plots of the two isostructural pairs are comparable The FPs of
3.2. Structural description of MT(4′‐CF3P)P (2a−2d)
Compounds,
2a | 2b | 2c | 2d | |
---|---|---|---|---|
Empirical formula | C56H42F12N4O2 | C56H40F12N4NiO2 | C52H32CuF12N4O | C52H32F12N4OZn |
Fw | 1030.94 | 1087.63 | 1020.36 | 1022.19 |
CCDC no. | 1013690 | 1013689 | 1011088 | 1011087 |
Colour | Purple | Violet | Brown | Brown |
Crystal system | Triclinic | Monoclinic | Triclinic | Monoclinic |
Space group | P‐1 | P21/n | P‐1 | P21/c |
a, Å | 11.5014(8) | 14.5791(19) | 9.7136(5) | 19.427(3) |
b, Å | 13.1179(12) | 9.5303(19) | 14.5452(9) | 9.3940(10) |
c, Å | 17.3269(15) | 18.351(4) | 16.8870(13) | 25.466(5) |
a, (°) | 96.329(3) | 90.0 | 76.608(3) | 90.0 |
β, (°) | 92.833(3) | 101.571(8) | 89.617(3) | 102.756(5) |
γ, (°) | 108.739(3) | 90.0 | 76.676(3) | 90.0 |
Volume (Å3) | 2450.5(4) | 2498.0(8) | 2255.8(3) | 4532.8(12) |
Z | 2 | 2 | 2 | 4 |
Dcalcd(mg/m3) | 1.397 | 1.446 | 1.502 | 1.498 |
λ, Å | 0.71073 | 0.71073 | 0.71073 | 0.71073 |
T (K) | 173 | 173 | 173 | 173 |
No. of unique reflections | 8528 | 4413 | 7810 | 7986 |
No. of parameters refined | 788 | 397 | 825 | 813 |
GOF on F2 | 1.027 | 1.015 | 1.039 | 1.022 |
R1b | 0.0657 | 0.0477 | 0.0476 | 0.0465 |
wR2c | 0.1849 | 0.1179 | 0.1205 | 0.1129 |
The copper(II) centre in
The zinc(II) centre in
The geometrical analysis of porphyrins,
The crystal packing in porphyrins
Apart from this, porphyrin
3.3. Structural description of MTF4DMAP (3a−3d)
Porphyrins
Empirical formula | C52H40F16N8O2 | C60H48F16N8NiO2 | C52H36CuF16N8O2 | C64H56F16N8O3Zn |
Fw | 1112.92 | 1275.77 | 1172.43 | 1354.54 |
Color | Purple | Pink | Red | Purple |
Crystal system | Triclinic | Tetragonal | Triclinic | Tetragonal |
Space group | P‐1 | P42/n | P‐1 | I4 |
a, Å | 10.2706(5) | 15.9979(5) | 10.2273(5) | 16.4305(3) |
b, Å | 14.6333(7) | 15.9979(5) | 14.6303(6) | 16.4305(3) |
c, Å | 18.0523(9) | 10.9552(7) | 17.9791(7) | 11.1822(5) |
α, (°) | 86.258(2) | 90 | 86.664(2) | 90 |
β, (°) | 86.484(2) | 90 | 86.704(2) | 90 |
γ, (°) | 74.150(2) | 90 | 74.494(2) | 90 |
vol (Å3) | 2601.7(2) | 2803.8(2) | 2585.42(19) | 3018.76(16) |
Z | 2 | 2 | 2 | 2 |
Dcalcd (mg/m3) | 1.421 | 1.511 | 1.506 | 1.490 |
wavelength (), Å | 0.71073 | 0.71073 | 0.71073 | 0.71073 |
T (K) | 293(2) | 293(2) | 293(2) | 293(2) |
No. of unique reflections | 6143 | 2169 | 5964 | 2605 |
No. of parameters refined | 798 | 197 | 779 | 221 |
GOF on F2 | 1.111 | 1.075 | 1.103 | 1.077 |
R1a | 0.0640 | 0.0522 | 0.0428 | 0.0410 |
wR2b | 0.1930 | 0.1529 | 0.1151 | 0.1083 |
Compound
The average Zn–N and Zn−O distance in
The HSs of molecules
3.4. Structural description of 5,15‐di(pentafluorophenyl)‐10,20‐bis(4′‐bromophenyl)porphyrin and its metal complexes (4a−4d)
Like other fluorinated porphyrins discussed earlier, the crystal packing of trans porphyrins
Empirical formula | C44H18Br2F10N4 | C54H26Br2F10FeN6 | C44H16Br2CuF10N4 | C52H32Br2F10N4O2Zn |
Fw | 952.44 | 1164.48 | 1013.97 | 1160.01 |
CCDC no. | 1013690 | 1013689 | 1011088 | 1011087 |
Colour | Purple | Red | Purple | Purple |
Crystal system | Monoclinic | Triclinic | Monoclinic | Triclinic |
Space group | P21/c | P‐1 | P21/c | P‐1 |
a, Å | 14.9457(6) | 10.700(5) | 14.8461(9) | 12.6848(5) |
b, Å | 8.9793(4) | 13.933(5) | 8.9921(5) | 13.4661(5) |
c, Å | 15.9316(6) | 17.329(5) | 15.8111(9) | 16.2952(6) |
α, (°) | 90 | 103.791(5) | 90 | 66.724(2) |
β, (°) | 116.550(2) | 100.709(5) | 116.115(3) | 68.750(2) |
T (K) | 293(2) | 293(2) | 293(2) | 293(2) |
, Å | 0.71073 | 0.71073 | 0.71073 | 0.71073 |
γ, (°) | 90 | 103.144(5) | 90 | 76.468(2) |
Volume (Å3) | 1912.58(14) | 2363.2(16) | 1895.26(19) | 2369.64(16) |
Z | 2 | 2 | 2 | 2 |
Dcalcd (mg/m3) | 1.654 | 1.636 | 1.777 | 1.626 |
No. of unique reflections | 3747 | 6952 | 3340 | 8341 |
No. of parameters refined | 277 | 661 | 277 | 854 |
GOF on F2 | 1.022 | 1.057 | 1.025 | 1.024 |
R1b | 0.0465 | 0.0551 | 0.0448 | 0.0586 |
wR2c | 0.1317 | 0.1395 | 0.1131 | 0.1468 |
The prominent spikes in the FP plots of
The C∙∙∙H contact is seen as peripheral wing like structure in all the four porphyrins and is associated with 13–18% of the total HSs. The H∙∙∙H interactions are more pronounced in iron and zinc derivative (21–22%), and it contributes only 7–10% for the isostructural pair
4. Conclusions
In conclusion, we have demonstrated the results of experimental crystallographic studies combined with computational HS analysis of a series of fluorinated porphyrins,
Acknowledgments
SS (SR/WOS‐A/CS‐146/2011) and CA (SR/FT/CS‐25/2011, SB/EMEQ‐016/2013 and FRG 10‐11/0103) thank DST, New Delhi and NIT Calicut for research funding. The authors thank the students of Bioinorganic Materials Chemistry Laboratory, Department of Chemistry, National Institute of Technology Calicut, namely Rahul Soman, Fasalu Rahman Kooriyaden and Ramesh J for their contributions. We would like to thank Dr. Shibu M. Eappen, STIC, CUSAT, Kochi and Dr. Babu Varghese, SAIF, IIT Madras for the single crystal data collection and structure solution, refinement respectively. The authors also thank Prof. T. N. Guru Row and Mr. Vijith kumar, Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore for their help to get one of the single crystal X‐ray data collections.
References
- 1.
Hoard JL: In Smith KM, editor. Stereochemistry of Porphyrins and metalloporphyrins. New York: Elsevier; 1975, pp. 317–380. - 2.
Rothemund P: A new porphyrin synthesis. The synthesis of porphin. J. Am. Chem. Soc. 1936; 58 :625–627. doi:10.1021/ja01295a027 - 3.
Adler AD, Longo FR, Kampas F, Kim J: On the preparation of metalloporphyrins. J. Inorg. Nucl. Chem. 1970; 32 :2443–2445. doi:10.1016/0022‐1902(70)80535‐8 - 4.
Adler AD, Longo FR, Finarelli JD, Goldmacher J, Assour J, Korsakoff L: A simplified synthesis for meso ‐tetraphenylporphin. J. Org. Chem. 1967;32 :476. doi:10.1021/jo01288a053 - 5.
Lindsey JS, Wagner RW: Investigation of the synthesis of ortho ‐substituted tetraphenylporphyrins. J. Org. Chem. 1989;54 :828–836. doi:10.1021/jo00265a021 - 6.
Lindsey JS, Schreiman IC, Hsu HC, Kearney PC, Marguerettaz AM: Rothemund and Adler–Longo reactions revisited. Synthesis of tetraphenylporphyrins under equilibrium conditions. J. Org. Chem. 1987; 52 :827–836. doi:10.1021/jo00381a022 - 7.
Maldotti A, Amadelli R, Bartocci C, Carassiti V, Polo E, Varani G: Photochemistry of Iron‐porphyrin complexes. Biomimetics and catalysis. Coord. Chem. Rev. 1993; 125 :143–154. doi:10.1016/0010‐8545(93)85014‐U - 8.
Chou JH, Kosal ME, Nalwa HS, Rakow NA, Suslick KS: Applications of porphyrins and metalloporphyrins to materials chemistry. Urbana: Academic Press; 2000. - 9.
Sternberg ED, Dolphin D, Brickner C: Porphyrin‐based photosensitizers for use in photodynamic therapy. Tetrahedron. 1998; 54 :4151–4202. doi:10.1016/S0040‐4020(98)00015‐5 - 10.
Rashid H, Umar MN, Khan K, Anjum MN, Yaseen M: Synthesis and relaxivity measurement of porphyrin‐based magnetic resonance imaging (MRI) contrast agents. J. Struct. Chem. 2014; 55 :910–915. doi:10.1134%2FS0022476614050163 - 11.
Ethirajan M, Chen Y, Joshia P, Pandey RK: The role of porphyrin chemistry in tumor imaging and photodynamic therapy. Chem. Soc. Rev. 2011; 40 :340–362. doi:10.1039/B915149B - 12.
Ojima I, editor. Fluorine in medicinal chemistry and chemical biology. UK: Wiley‐Blackwell; 2009. - 13.
DiMagno SG, Biffinger JC, Sun H: Fluorinated porphyrins and corroles: Synthesis, electrochemistry, and applications. Fluor. Heterocycl. Chem. 2014; 1 :589–620. doi:10.1007/978‐3‐319‐04346‐3_14 - 14.
Berger R, Resnati G, Metrangolo P, Weberd E, Hulliger J: Organic fluorine compounds: A great opportunity for enhanced materials properties. Chem. Soc. Rev. 2011; 40 :3496–3508. doi:10.1039/C0CS00221F - 15.
Desiraju GR. Crystal engineering: The design of organic solids. Amsterdam: Elsevier; 1989. - 16.
Chopra D, Guru Row TN. Role of organic fluorine in crystal engineering. CrystEngComm. 2011; 13 :2175–2186. doi:10.1039/C0CE00538J - 17.
Goldberg I. Crystal engineering of porphyrin framework solids. Chem. Commun. 2005;1243–1254. doi:10.1039/B416425C - 18.
Spackman MA, Jayatilaka D. Hirshfeld surface analysis. CrystEngComm. 2009; 11 :19–32. doi:10.1039/B818330A - 19.
Wolff SK, Grimwood DJ, McKinnon JJ, Turner MJ, Jayatilaka D, Spackman MA. Crystal Explorer 3.1 (2013), University of Western Australia, Crawley, Western Australia, 2005–2013. http://hirshfeldsurface.net/CrystalExplorer . - 20.
McKinnon JJ, Mitchell AS, Spackman MA: Hirshfeld surfaces: A new tool for visualising and exploring molecular crystals. Chem. Eur. J. 1998; 4 :2136–2141. doi:10.1002/(SICI)1521‐3765(19981102)4:11<2136::AID‐CHEM2136>3.0.CO;2‐G - 21.
Spackman MA, McKinnon JJ: Fingerprinting intermolecular interactions in molecular crystals. CrystEngComm. 2002; 4 :378–392. doi:10.1039/b203191b - 22.
Littler BJ, Ciringh Y, Lindsey JS: Investigation of conditions giving minimal scrambling in the synthesis of trans ‐porphyrins from dipyrromethanes and aldehydes. J. Org. Chem. 1999;64 :2864–2872. doi:10.1021/jo982452o - 23.
Adler AD, Longo FR, Kampas F, Kim J: On the preparation of metalloporphyrins. J. Inorg. Nucl. Chem. 1970; 32 :2443–2445. doi:10.1016/0022‐1902(70)80535‐8 - 24.
Altomare AG, Cascarano G, Giacovazzo C, Gualardi A: Completion and refinement of crystal structures with SIR92. J. Appl. Crystallogr. 1993; 26 :343–350. doi:10.1107/S0021889892010331 - 25.
Sheldrick GM. SHELXL97. Goettingen, Germany: University of Goettingen; 1997. - 26.
Kadish KM, Araullo‐McAdams C, Han BC, Franzen MM: Syntheses and spectroscopic characterization of (T(p‐Me2N)F4PP)H2 and (T(p‐Me2N)F4PP)M. J. Am. Chem. Soc. 1990; 112 :8364–8368. doi:10.1021/ja00179a021 - 27.
Schauer CK, Anderson OP, Eaton SS, Eaton GR: Crystal and molecular structure of a six‐coordinate zinc porphyrin: Bis(tetrahydrofuran)(5,10,15,20‐tetraphenylporphinato)zinc(II). Inorg. Chem. 1985; 24 :4082–4086. doi:10.1021/ic00218a024 - 28.
Tarahhomi A, Pourayoubi M, Golen JA, Zargaran P, Elahi B, Rheingold AL, Leyva Ramırezc MA, Percino TM: Hirshfeld surface analysis of new phosphoramidates. Acta Cryst. 2013; B69 :260–270. doi:10.1107/S2052519213009445 - 29.
Bondi A: Van der Waals volumes and radii. J. Phys. Chem. 1964; 68 :441–451. doi:10.1021/j100785a001 - 30.
Batsanov SS: Van der Waals radii of elements. Inorg. Mater. 2001; 37 :871–885. doi:10.1023/A:1011625728803 - 31.
Grabowsky S, Dean PM, Skelton BW, Sobolev AN, Spackman MA, White AH: Crystal packing in the 2‐R,4‐oxo‐[1,3‐a/b]‐naphthodioxanes–Hirshfeld surface analysis and melting point correlation. CrystEngComm. 2012; 14 :1083–1093. doi:10.1039/c2ce06393j - 32.
Soman R, Sujatha S, Arunkumar C: Quantitative crystal structure analysis of fluorinated porphyrins. J. Fluor. Chem. 2014; 163 :16–22. doi:10.1016/j.jfluchem.2014.04.002 - 33.
Reed CA, Mashiko T, Scheidt WR, Spartalian K, Lang G: High spin iron (II) in the porphyrin plane. Structural characterization of (mesotetraphenylporphinato) bis (tetrahydrofuran)iron (II). J. Am. Chem. Soc. 1980; 102 :2302–2306. doi:10.1021/ja00527a028 - 34.
Schauer CK, Anderson OP, Eaton SS, Eaton GR: Crystal and molecular structure of a six‐coordinate zinc porphyrin: Bis(tetrahydrofuran) (5,10,15,20‐ tetraphenylporphinato) zinc(II). Inorg. Chem. 1985; 24 :4082–4086. doi:10.1021/ic00218a024 - 35.
Bhyrappa P, Arunkumar C: Structural and electrochemical properties of β‐tetrabromo‐mesotetrakis(4‐alkyloxyphenyl)porphyrins and their metal complexes. J. Chem. Sci. 2010; 122 :233–238. doi:10.1007/s12039‐010‐0027‐6 - 36.
Bhyrappa P, Arunkumar C, Varghese B, Sankara Rao DS, Prasad SK: Synthesis and mesogenic properties of β‐tetrabrominated tetraalkyloxyporphyrins. J. Porphyrins Phthalocyanines. 2008; 12 :54–64. doi:10.1142/S108842460800008X - 37.
Scheidt WR: Systematics of the stereochemistry of porphyrins and metalloporphyrins, Kadish KM, Smith KM, Guilard R, New York: Academic Press; 2000, vol. 3, pp. 49–112. - 38.
Kooriyaden FR, Sujatha S, Arunkumar C: Synthesis, spectral, structural and antimicrobial studies of fluorinated Porphyrins. Polyhedron. 2015; 97 :66–74. doi:10.1016/j.poly.2015.05.018 - 39.
Soman R, Sujatha S, De S, Rojisha VC, Parameswaran P, Varghese B, Arunkumar C: Intermolecular Interactions in fluorinated tetraarylporphyrins: An experimental and theoretical study. Eur. J. Inorg. Chem. 2014;2653–2662. doi:10.1002/ejic.201402008