Supramolecular Organic and Organometallic Chemistry Centre

Results 2015

A major goal concerning the synthesis of different types of cryptands was connected to the access to aromatic reference units with different functional groups and the large scale obtaining of the reagents for the bridges (the real bottleneck of our targets).
a) Synthesis of tetrasubstituted derivatives of pyrene with one or two types of substituents and of the derivatives of triphenyltriazine bearing two types of substrituents (Scheme 1).
b) Efficient synthesis of the derivatives of phenantroline designed for in and out bridges (Schemes 2 and 3).

Another important goal is connected to the development of the active template synthesis for our targets (less steps, simplest reactions).
a) Synthesis of cryptands and linkers for the access to interlocked molecules using the "active-template" approach (Schemes 4-6)[1]


Other exciting cryptands were obtained in the stage 2014 accordingly to schemes 7 and 8.
In this stage (2015) the complexation ability of these cryptands were investigated using as guests the dications of aromatic diamines. The complexation of the dication of 1,5-nafphthalinediamine was investigated by ES-HRMS and NMR. Figures 1 and 2 show the spectra of the host, guest and host-guest species and the results of the NMR titration (Job-plot) which reveals the 1/1 guest / host ratio.



With an “all in” cryptand which was prepared previously we carried out complexation studies using aromatic guests (pyrene, anthracene) in order to explore the methodology for the investigation of the interactions among cryptands and aromatic guests (Scheme 9). The used methods were based on NMR, UV-VIS and Cyclic Voltammetry.
[1] Gil-Ramirez, G.; Leigh, D. A., Stephens, A. J. Angew. Chem. Int. Ed., 2015, 54, 6110-6150.

Results 2015

Due to the difficulty encountered in the purification process of the previously synthesized target molecules, a new strategy was envisioned.
The “active-metal-template” strategy (in which the heteroatoms from the arms take part to the formation of the required catalyst of the coupling reactions, leading to mechanically interlocked products [Gil-Ramírez, G.; Leigh, D. A., Stephens, A. J. Angew. Chem. Int. Ed., 2015, 54, 6110-6150]) simplifies the synthetic process, reduces the number of steps and leads to smaller and less complex compounds, facilitating their structural characterization along with a more efficient investigation of properties.
In this context, cryptand 1 and reactant 2 were synthesized in order to test the “active-metal-template” technique and to obtain mechanically interlocked compounds like macrocycles encapsulated inside cryptands (Scheme 1).
Having these components, an attempt was made to synthesize a mechanically interlocked derivative, in which the macrocycle would be trapped inside the cavity of the cryptand. The reaction took place with surprisingly high yields (40%) and the trimeric macrocycle 3 (Scheme 2) was exclusively obtained.
Unfortunately the macrocycle, which undoubtedly was formed (likewise the model from Scheme 3), managed to “escape” the cavity.

Job’s plot experiments (¹H NMR titrations) performed on compounds 1 and 3 did not show any significant interactions in solution, so, the formation of the mechanically interlocked compound could not be taken into consideration by these experiments. The “click” reaction of 2 in presence of pyridine instead of derivative 1, determined the formation of the macrocycle in lower yields (15%) and the formation of dimers, trimers and tetramers (identified in ESI-MS) as main products was observed. Even the reaction did not yield the desired mechanically interlocked compound, the result is particularly interesting due to its application of “active-metal-template” strategy in obtaining well-defined compounds like the previously mentioned trimer. This aspect has to be further investigated and the results will be published. In order to highlight the result and to obtain new compounds similar to the ones proposed in the project, we synthesized reactants of type 2 with longer arms, such as 4 and 5, (Scheme 4 and 5), capable of reacting either with cryptands of type 1 or with analogue cryptands having a single arm with heterocyclic units (6, n = 2, Scheme 6).


The macrocycles 1, 6 and compounds 4, 5 will be subjected to the “active-metal template” procedure in order to obtain cryptands in which the macrocycle will be able to perform movement controlled by supramolecular interactions, which involves various units of the macrocycle. The controlling will be made by complexation-decomplexation process or by modifying the pH.
The main objective of strategy D facilitates the obtaining of the desired compounds by using procedures and concepts for more accessible structures as compared to the initially proposed compounds.
Another direction of this research was the synthesis of cyclophanes and cryptands with 1,3-phenothiazine units in arms (Schemes 7 and 8). These compounds contain inwards directed functionalized arms and a priori could lead to the target mechanically interlocked structures. The reaction yields for obtaining cyclophanes 13-16 were good in both used methods, the procedure involving intermediates as well as in the “one pot” procedure.
However, in case of cryptand 17 only “one pot” method gave good results. Complexation studies revealed interesting results for cations and organic compounds as guests. Experiments with lead and cadmium cations (Figure 1) have allowed the construction of fluorescent molecular logic gates of type XOR (Table 1)



Phenothiazine-based cyclophanes and cryptands showed high versatility for performing synthesis of mechanically interlocked molecules. These experiments will be further continued.
In order to achieve project objectives other substrates were taken into consideration and several Bannister type macrocycles (Scheme 9) having ortho-disubstituted biphenylic units were obtained via oxime derivative. We expected the reactions will lead to dimers (2+2 reaction), which would have been interesting compounds for project. Surprisingly, only monomers resulted from the reaction. These compounds were investigated by NMR spectroscopy, MS spectrometry and the enantiomers were discriminated on chiral columns. The compounds exhibit affinity for various cations, and this property has been demonstrated both by NMR titration and by fluorescence investigations. Also for this case, the “active template” experiments will be performed.
In conclusion, the project objectives have been achieved and the proposed activities were carried out such that some of the target compounds were obtained and investigated, while the rest of investigations have to be further completed. The “activ-template” technique was proved to be the most effective and the results obtained by this method are notable and will be next published.
So far, 3 articles were published in organic chemistry and supramolecular chemistry related journals and other 3 articles will be sent in order to be published this year (the investigations are in the final stage at this moment).
At least two other papers will be published with the results of the undergoing experiments. In project were involved three PhD students and more Master‘s and Bachelor students. The dissemination activity has been also achieved by five plenary conferences, keynote or invited professors and several oral presentations and posters.