Laboratory Experiment Cite This: J. Chem. Educ. XXXX, XXX, XXX−XXX
pubs.acs.org/jchemeduc
A Rapid and Straightforward Supramolecular Self-Assembly Experiment To Prepare and Characterize a Triple Helicate Complex Nicholas G. White* Research School of Chemistry, The Australian National University, Canberra, Australian Capital Territory 2601, Australia S Supporting Information *
ABSTRACT: This experiment prepares a large (Mr: 1821 g mol−1) triple helicate complex quickly in one pot from inexpensive starting materials. The protocol illustrates the power of self-assembly in a simple manner that is suitable for second-year general chemistry students using reversible imine bond and metal−ligand bond formation. Plastic molecular models and 1H NMR spectroscopy are used to elucidate the structure of the selfassembled product.
KEYWORDS: Second-Year Undergraduate, Inorganic Chemistry, Organic Chemistry, Hands-On Learning/Manipulatives, Coordination Compounds, Laboratory Instruction
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upramolecular self-assembly is one of the major themes of modern coordination chemistry and has been used to prepare a range of complex materials including interlocked structures, knots, cage compounds, and metal organic frameworks (MOFs).1−3 Metal helicates are one of the simpler classes of metallosupramolecular architectures but still represent relatively complicated (and potentially large) entities, and are inherently chiral due to the helical twist of the ligands about the metal ions.4 Hannon’s group has demonstrated that triple helicates such as compound 14+ (Figure 1) can be prepared from inexpensive starting materials,5 and in certain cases can bind to the DNA major groove in a manner similar to zinc finger units.6,7 Given that the topic of supramolecular assembly bridges inorganic and organic chemistry and has relevance to biological and materials chemistry, it is perhaps surprising that there are relatively few undergraduate experiments that investigate it. As part of a redeveloped second-year undergraduate curriculum,
we teach the basic principles of metal-templated self-assembly, focusing on the use of reversible bond formation as a mechanism for error correction and hence achieving thermodynamic reaction control. We wished to support these concepts with a laboratory experiment, but were unable to find a suitable experiment that would demonstrate metal-templated assembly quickly and easily. While a number of undergraduate self-assembly experiments have been reported, many of these do not involve transition metals,9−12 which are the focus of our lecture material. Other elegant experiments have been reported but are too complex or have too high a level of theory for a second-year general undergraduate class.13−16 In this experiment, students use two different reversible reactions: metal−ligand bond formation and imine condensation to assemble a Fe2L3 helicate17 at ambient temperature within 15 min (L = a bis-bidentate ligand, Scheme 1). While the literature reports the preparation of these complexes over several hours at reflux, this procedure is conducted in minutes at ambient temperature. The reaction starts from simple, inexpensive materials and involves the formation of 12 metal− ligand bonds and 6 imine bonds in one pot to give a single racemic reaction product.
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LEARNING GOALS
This experiment was designed to fit in with a coordination chemistry curriculum and to reinforce several key concepts that we teach in this (second-year) course: Figure 1. Structure of Fe2L3 helicate 14+. Hydrogen atoms and PF6− counterions omitted for clarity, with each ligand shown in a different color. Figure generated from CCDC-622770.8 © XXXX American Chemical Society and Division of Chemical Education, Inc.
Received: September 1, 2017 Revised: January 16, 2018
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DOI: 10.1021/acs.jchemed.7b00674 J. Chem. Educ. XXXX, XXX, XXX−XXX
Journal of Chemical Education
Laboratory Experiment
Scheme 1. Synthesis of 1·4PF6a
a
spectrometer is an issue, raw 1H NMR data (FIDs) are provided as Supporting Information. Students also collect a UV−vis spectrum of their product and determine the molar extinction coefficient. While students are told the molecular mass of the product (as this is necessary to determine the molar extinction coefficient from the UV−vis spectrum), they are not given the structure; instead, students use molecular models to determine for themselves the nature of their reaction product. Simple plastic models of the reagents are provided, and students consider the possible reactions and prepare a model of their product (see Figure 2 and Instructor Notes in the Supporting Information).
The structure of 1·4PF6 is shown in Figure 1.
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• Self-assembly: A large number of bond forming reactions, both organic and coordination, take place in “one pot,” and yet only one product is observed due to the reversible nature of these reactions. • Reactivity: Students are told that the imine-forming reaction takes many hours in the absence of a metal ion and are asked to explain why iron(II) accelerates the reaction. This reinforces the key theme that metal− ligand coordination affects the properties of both the metal and ligand, and could potentially be used to lead into a more in-depth discussion of catalysis. • Color: Students prepare a highly colored complex, and are asked about the origin of this color, requiring them to consider the nature of the metal ion and ligand, and selection rules. • Small scale synthesis: Students work on a relatively small scale (∼100 mg of most reagents). This requires precise measuring, and provides a more realistic model for research-scale chemistry. • Bridging the inorganic−organic divide: While this is nominally an “inorganic” laboratory, students conduct an organic reaction, analyze a product by 1H NMR spectroscopy, and answer questions on chiral separation, all concepts that are more traditionally considered to be part of organic chemistry.
EXPERIMENT The experiment takes most students approximately 2.5 h to complete including synthesis and characterization. Students work individually and complete a risk assessment and brief prelab quiz beforehand. Students add a solution of iron(II) chloride tetrahydrate (1.0 mol equiv) in methanol to 4,4′methylenedianiline (1.5 mol equiv) in methanol; 2-pyridinecarboxaldehyde (slight excess) is then added using a micropipette. After stirring for 15 min at room temperature, a solution of ammonium hexafluorophosphate in methanol is added, resulting in the precipitation of 14+ as the PF6− salt as a deep purple powder, which is washed with methanol and dried. The cost of reagents on this scale is less than US $0.50/ student.18 Each student prepares a sample in d6-acetone for 1H NMR analysis: these samples are analyzed by a demonstrator and the spectra sent to students through an online interface.19 The purity of the compound as determined by NMR spectroscopy makes up a small amount of the students’ grade for this experiment. If the cost of NMR solvents or access to an NMR
Figure 2. (A) Examples of disassembled molecular models provided to students. (B) A successfully modeled helicate. Other types of molecular models were also successfully used (see Instructor Notes in the Supporting Information).
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HAZARDS Students must wear safety glasses and laboratory coats at all times. Ammonium hexafluorophosphate and iron(II) chloride tetrahydrate are corrosive; methanol and acetone are highly flammable and toxic. Pyridine-2-carboxaldehyde is toxic and may cause an allergic skin reaction. Methylene-4,4′-dianiline is toxic and is a suspected carcinogen. Given the ability of the [Fe2L3]4+ complex product to interact with DNA,6,7 this should be treated with caution. Students are required to prepare a risk assessment and answer prelab questions, which specifically highlight that one compound (methylene-4,4′-dianiline) is B
DOI: 10.1021/acs.jchemed.7b00674 J. Chem. Educ. XXXX, XXX, XXX−XXX
Journal of Chemical Education
Laboratory Experiment
incorporates aspects of organic and inorganic chemistry, and ties in with key concepts in both fields.
particularly toxic, and ask students what steps they will take to counter this. The risk assessment and questions are checked by a demonstrator before any experimental work is started.
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ASSOCIATED CONTENT
S Supporting Information *
RESULTS AND DISCUSSION This experiment has been performed in a second-year general chemistry course with approximately 110 enrolled students, and was the last of eight laboratory sessions (four organic and three inorganic laboratories had been completed prior to this). Students in this course have also completed two first-year general chemistry courses. Students (30−40) completed the laboratory on each of 3 days. Of the 103 students who submitted a report for assessment, 100 obtained a yield ≥50% (mean yield: 73%20). While this is not as high as when the reaction were carried out by more highly trained chemists (two fourth-year undergraduate students and the author obtained yields of ∼90% under the same conditions), this suggests that students were able to cope relatively well with the small scale reaction. All students observed the expected absorbance in the UV−vis spectrum (observed λmax: 569−580 nm), although the reported molar extinction coefficients varied widely partly due to errors in calculation. While many students struggled to correctly determine this value, nearly all students were still able to recognize that ε was too high for the color to arise from d−d transitions alone. The vast majority of students (97/103) supplied a good quality 1H NMR spectrum of their complex and were able to assign all groups of resonances. The remaining six students either did not submit a spectrum, or submitted a “model” spectrum provided to them. Pleasingly, very few students had visible impurities in their NMR spectra, and in most cases no solvent resonances were present (apart from the residual NMR solvent resonance and water, see Figure 3 for a representative student spectrum).
The Supporting Information is available on the ACS Publications website at DOI: 10.1021/acs.jchemed.7b00674. Instructor notes (PDF, DOCX) Student handouts (PDF, DOCX) 1 H NMR raw data (ZIP)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Nicholas G. White: 0000-0003-2975-0887 Notes
The author declares no competing financial interest.
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ACKNOWLEDGMENTS This work would not have been possible without the help of a large number of colleagues: the author would like to thank Dr. Jonathan Beves (University of New South Wales) for suggesting the helicates as possible candidates for an undergraduate experiment, Dr. Mark Ellison and Dr. Jas Ward (ANU) for insightful comments on the manuscript, ANU chemistry teaching for financial support, Avis Patterson for technical assistance, Harrison Barnett and Richard Kong for checking the experimental procedure, James Culvenor for preparing the compound used in Figure 3, Drs. Amedée Triadon and Mahbod Morshedi for assistance collecting NMR spectra, and Runli “Jerry” Wang [left] and Supanimit Chiampanichayakul [right] for assistance with the abstract graphic.
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REFERENCES
(1) Yaghi, O. M.; O’Keeffe, M.; Ockwig, N. W.; Chae, H. K.; Eddaoudi, M.; Kim, J. Reticular synthesis and the design of new materials. Nature 2003, 423, 705−714. (2) Cook, T. R.; Zheng, Y.-R.; Stang, P. J. Metal-Organic Frameworks and Self-Assembled Supramolecular Coordination Complexes: Comparing and Contrasting the Design, Synthesis, and Functionality of Metal-Organic Materials. Chem. Rev. 2013, 113, 734−777. (3) Beves, J. E.; Blight, B. A.; Campbell, C. J.; Leigh, D. A.; McBurney, R. T. Strategies and Tactics for the Metal-Directed Synthesis of Rotaxanes, Knots, Catenanes, and Higher Order Links. Angew. Chem., Int. Ed. 2011, 50, 9260−9327. (4) Piguet, C.; Bernardinelli, G.; Hopfgartner, G. Helicates as Versatile Supramolecular Complexes. Chem. Rev. 1997, 97, 2005− 2062. (5) Hannon, M. J.; Painting, C. L.; Jackson, A.; Hamblin, J.; Errington, W. An inexpensive approach to supramolecular architecture. Chem. Commun. 1997, 1807−1808. (6) Meistermann, I.; Moreno, V.; Prieto, M. J.; Moldrheim, E.; Sletten, E.; Khalid, S.; Rodger, P. M.; Peberdy, J. C.; Isaac, C. J.; Rodger, A.; Hannon, M. J. Intramolecular DNA coiling mediated by metallo-supramolecular cylinders: Differential binding of P and M helical enantiomers. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 5069− 5074. (7) Hannon, M. J.; Moreno, V.; Prieto, M. J.; Moldrheim, E.; Sletten, E.; Meistermann, I.; Isaac, C. J.; Sanders, K. J.; Rodger, A. Intramolecular DNA Coiling Mediated by a Metallo-Supramolecular Cylinder. Angew. Chem., Int. Ed. 2001, 40, 879−884.
Figure 3. 1H NMR spectrum of 1·4PF6 prepared by a student (400 MHz, 293 K, d6-acetone; peak marked * corresponds to residual C3HD5O, peak marked # corresponds to water).
As well as the learning goals discussed above, this experiment exposes students to a range of new techniques, including using micropipettes, and preparing samples for NMR analysis. While this experiment has been designed for a second-year class, a higher level student-directed undergraduate exploratory project using different metal ions and varying diamine and aldehyde components could also be envisaged (see Instructor Notes in the Supporting Information).5,8,21,22
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SUMMARY A laboratory experiment has been devised allowing for a rapid and simple demonstration of supramolecular self-assembly from inexpensive commercially available precursors. This procedure C
DOI: 10.1021/acs.jchemed.7b00674 J. Chem. Educ. XXXX, XXX, XXX−XXX
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(8) Kerckhoffs, J. M. C. A.; Peberdy, J. C.; Meistermann, I.; Childs, L. J.; Isaac, C. J.; Pearmund, C. R.; Reudegger, V.; Khalid, S.; Alcock, N. W.; Hannon, M. J.; Rodger, A. Enantiomeric resolution of supramolecular helicates with different surface topographies. Dalton Trans. 2007, 734−742. (9) Stals, P. J. M.; Haveman, J. F.; Palmans, A. R. A.; Schenning, A. P. H. J. The Self-Assembly Properties of a Benzene-1,3,5-tricarboxamide Derivative. J. Chem. Educ. 2009, 86, 230−233. (10) Jensen, J.; Grundy, S. C.; Bretz, S. L.; Hartley, C. S. Synthesis and Characterization of Self-Assembled Liquid Crystals: p-Alkoxybenzoic Acids. J. Chem. Educ. 2011, 88, 1133−1136. (11) Cannon, A. S.; Warner, J. C.; Koraym, S. A.; Marteel-Parrish, A. E. Noncovalent Derivatization: A Laboratory Experiment for Understanding the Principles of Molecular Recognition and Self-Assembly through Phase Behavior. J. Chem. Educ. 2014, 91, 1486−1490. (12) Smith, M. K.; Angle, S. R.; Northrop, B. H. Preparation and Analysis of Cyclodextrin-Based Metal−Organic Frameworks: Laboratory Experiments Adaptable for High School through Advanced Undergraduate Students. J. Chem. Educ. 2015, 92, 368−372. (13) Pentecost, C. D.; Tangchaivang, N.; Cantrill, S. J.; Chichak, K. S.; Peters, A. J.; Stoddart, J. F. Making Molecular Borromean Rings. A Gram-Scale Synthetic Procedure for the Undergraduate Organic Lab. J. Chem. Educ. 2007, 84, 855−859. (14) Sumida, K.; Arnold, J. Preparation, Characterization, and Postsynthetic Modification of Metal−Organic Frameworks: Synthetic Experiments for an Undergraduate Laboratory Course in Inorganic Chemistry. J. Chem. Educ. 2011, 88, 92−94. (15) Fernández, A.; López-Torres, M.; Fernández, J. J.; VázquezGarcía, D.; Vila, J. M. A One-Pot Self-Assembly Reaction To Prepare a Supramolecular Palladium(II) Cyclometalated Complex: An Undergraduate Organometallic Laboratory Experiment. J. Chem. Educ. 2012, 89, 156−158. (16) Go, E. B.; Srisuknimit, V.; Cheng, S. L.; Vosburg, D. A. SelfAssembly, Guest Capture, and NMR Spectroscopy of a Metal− Organic Cage in Water. J. Chem. Educ. 2016, 93, 368−371. (17) This reaction gives both enantiomers of the inherently chiral helicate; the separation of these isomers using chromatography on cellulose has been previously reported (see ref 8). We attempted to find a way to incorporate separation of the enantiomers into this experiment but could not find a simple way to do this (see Instructor Notes in the Supporting Information). (18) US Sigma-Aldrich prices (July 2017): iron chloride tetrahydrate $188.50 for 1 kg; methylene-4,4′-dianiline $92.50 for 1 kg; pyridine-2carboxaldehyde $221 for 500 g; ammonium hexafluorophosphate $181 for 100 g. Cost of reagents per student on scale described: 38 cents. Other suppliers may be cheaper than this (particularly for ammonium hexafluorophosphate). (19) It is expected that the helicate will be suitable for benchtop NMR analysis due to its high solubility and the well-separated resonances, see Figure 3 (we do not have access to benchtop NMR spectrometers). (20) This analysis excludes eight students who reported yields > 100%. Interestingly, the 1H NMR spectrum of these students’ compounds indicated clean product, without solvent contamination, so it is unclear where these inflated yields arose. (21) Hannon, M. J.; Painting, C. L.; Alcock, N. W. A metallosupramolecular double-helix containing a major and a minor groove. Chem. Commun. 1999, 2023−2024. (22) Tuna, F.; Lees, M. R.; Clarkson, G. J.; Hannon, M. J. Readily Prepared Metallo-Supramolecular Triple Helicates Designed to Exhibit Spin-Crossover Behaviour. Chem. - Eur. J. 2004, 10, 5737−5750.
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DOI: 10.1021/acs.jchemed.7b00674 J. Chem. Educ. XXXX, XXX, XXX−XXX
