Final Report Summary - NANOBIOMOFS (Nanoscale Metal–Organic Frameworks for Biomedical Applications)
The aim of the project with acronym of NanoBioMOFs (Nanoscale Metal–Organic Frameworks for Biomedical Applications) was to develop known and novel MOFs based on several multifunctional and bio-related ligands such as amino acids, peptides and nucleobases and miniaturise them at the nanoscale regime in order to be tested in vitro to evaluate their toxicity and therapeutic efficacy. During the 24 months period of the Marie Curie fellowship, the fellow Dr Kyriakos Stylianou has enhanced his skills and background in nanotechnology and became an expert in using new methodologies such as Microfluidic-Pen Lithography for the controlled growth and reaction screening of MOFs on SiO2 substrates and Spray Drying for the synthesis of MOF based composites for energy- and bio-related applications.
During the fellowship (March 1st 2012 until March 1st 2014), the fellow has synthesized several novel materials based on nucleobases, peptides and synthetic amides. The resulting extended networks (14 in total) have been fully characterized by powder and single crystal X-ray diffraction, infra-red spectroscopy, thermogravimetric analysis, elemental analysis, SEM and TEM. Their sorption behavior was also assessed by measuring CO2 and N2 isotherms at 195K and 77K, respectively, and the strength of interactions between guest molecules and host framework was calculated using the adsorption branches of the CO2 isotherms collected at 273 and 298K.
Adenine-based MOFs. Throughout this period the fellow isolated 4 novel adenine MOFs based on transition metals Co(II) and Zn(II) and tetracarboxylate linkers. It is found that the coordination of adenine around the metal cluster is different in all isolated MOFs, highlighting the rich coordination ability of adenine (from any of its five N-donor atoms) to coordinate. This versatility has a direct influence on the final behavior of the MOF, as for example: A. A 3D metal-organic framework (MOF) based on 1D Co-adeninate chains that are linked to a tetracarboxylate ligand shows colorimetric response from pink to purple upon dehydration. This change is indicative of extensive structural changes, as confirmed by powder X-ray diffraction and it is non-porous to N2 and CO2 suggesting found that the pore volume decreased – undergoing structural changes. The structure and pores of the as-made framework can be restored by hydration; and B. the Zn-porphyrin-adenine is a 3D anionic MOF in which adenine is a tridentate and bridging ligand. Interestingly, the Watson-Crick face of adenine is pointing within the pore - a key characteristic – which is already proposed in NanoBioMOFs, to form hydrogen bonding interactions with an anticancer drug such as 5-fluorouracil (5-FU), as observed in RNA between adenine and uracil. Solution isotherms of 5-FU monitored by UV/vis revealed that the drug can diffuse within the channels of the MOF. The former study (A) has been submitted for publication, whereas the latter (B) is in the final experimental stages and will be drafted and submitted for publication.
Peptide-based MOFs. A reticular family of novel 2D layered peptide based MOFs (7) is isolated varying the length of the pillar ligand used. Initially, 1D chains based on metal and peptide were synthesized and then the pillaring of the chains led to generation of 2D porous peptide based MOFs. The use of a small pillar ligand (bipyridyl) gave rise to a framework with pore size of 7 Å, whereas the largest ligand (bpeb) resulted in a MOF with the same topology but with pore size of 19 Å. This characteristic has a direct influence of the porosity and the BET surface area, increasing with the relative increase of the pillar ligand. This family of MOFs is very attractive due to their enhanced chemical and thermal stability, which is thought to be due to the strong H-interactions between the peptides. Racemic chiral molecules with different sizes and functionalities were loaded within all MOFs, and using GC-MS spectroscopy it was possible to separate the enantiomers. The peptide based MOF with the highest BET surface area and large pore size was used to separate the racemic mixture of the drug of ibuprofen as the enantiopure is the S-ibuprofen. These results present a new way to separate racemic drugs in which their enantiopurity is a key factor for their activity. This work is still in progress.
Polyamino acid based MOFs. The strategic design and synthesis of two chiral R- and S-tri-(aspartic acid) ligands and their subsequent use - varying the ratio between them, with Cu(II) under identical conditions has led to the formation of two isostructural and homochiral MOFs with opposite optical activity and a racemic network. For the first time, we have demonstrated that the enantioputity of the ligand used in the synthesis of MOFs is of high importance as it is the driving force for the structural topology of the MOF and consequently affecting their final properties. This work is drafted and submitted for publication.
During the 2 years of the fellowship, the fellow is represented as a co-author within three paper of high importance and advanced nanotechnological work based on the crystallization of MOFs on substrates using microfluidic pen lithography (Nature Communications, 2013), strategies to generate hollow superstructures (Chemistry – A European Chemisty, 2014) and finally dealing with CO2 capture (Crystal Growth and Design, 2014). The latter publication was the result of a collaboration with scientists from Tarbiat Modares University, Iran. Furthermore, a book chapter has been also accepted for publication in Wiley books 2014, giving an overview about the synthetic methodologies available for the isolation of nanoscale MOFs and their potential applications. He has also participated in five international conferences (2 poster and 3 oral presentations), where he has presented his results and interacted with scientists from other disciplines. In addition, the successful application for accessing Synchrotron facilities in Didcot, Oxford UK allowed him to collect data on samples that was not able to characterize using in house single crystal diffractometer; the obtained results are also presented in the Diamond Light Source 2013/14 Annual Review as a mini review.
One of the key role of the fellow within the NANOUP group is to acquire the very important and valuable experience through the supervision of projects and mentoring and tutoring master and postgraduate level students. The fellow has mentored 4 summer students, mentor a PhD student in collaboration with another institute ICMAB (Barcelona), and is also currently co-supervising the Thesis of a PhD student – Mr. Iván Burneo. In addition, he is also helping other group members with their projects and is involved in different projects as for example with scientists from Autonomous University of Madrid, Madrid.
In summary, the Marie Curie fellowship has been extremely productive and useful for his career and this is actually reflected by the interview invitations that he got as a junior group leader at the Jacobs University in Bremen, Germany and Ecole Polytecnique Federale Lausanne, Switzerland. While the 2 years of the fellowship were very beneficial in gaining of important scientific knowledge (dissemination of results, preparation of proposals for funding etc) and acquiring important qualities for the supervision of students, there is still some experimental work that needs to be completed and drafted for publication.
During the fellowship (March 1st 2012 until March 1st 2014), the fellow has synthesized several novel materials based on nucleobases, peptides and synthetic amides. The resulting extended networks (14 in total) have been fully characterized by powder and single crystal X-ray diffraction, infra-red spectroscopy, thermogravimetric analysis, elemental analysis, SEM and TEM. Their sorption behavior was also assessed by measuring CO2 and N2 isotherms at 195K and 77K, respectively, and the strength of interactions between guest molecules and host framework was calculated using the adsorption branches of the CO2 isotherms collected at 273 and 298K.
Adenine-based MOFs. Throughout this period the fellow isolated 4 novel adenine MOFs based on transition metals Co(II) and Zn(II) and tetracarboxylate linkers. It is found that the coordination of adenine around the metal cluster is different in all isolated MOFs, highlighting the rich coordination ability of adenine (from any of its five N-donor atoms) to coordinate. This versatility has a direct influence on the final behavior of the MOF, as for example: A. A 3D metal-organic framework (MOF) based on 1D Co-adeninate chains that are linked to a tetracarboxylate ligand shows colorimetric response from pink to purple upon dehydration. This change is indicative of extensive structural changes, as confirmed by powder X-ray diffraction and it is non-porous to N2 and CO2 suggesting found that the pore volume decreased – undergoing structural changes. The structure and pores of the as-made framework can be restored by hydration; and B. the Zn-porphyrin-adenine is a 3D anionic MOF in which adenine is a tridentate and bridging ligand. Interestingly, the Watson-Crick face of adenine is pointing within the pore - a key characteristic – which is already proposed in NanoBioMOFs, to form hydrogen bonding interactions with an anticancer drug such as 5-fluorouracil (5-FU), as observed in RNA between adenine and uracil. Solution isotherms of 5-FU monitored by UV/vis revealed that the drug can diffuse within the channels of the MOF. The former study (A) has been submitted for publication, whereas the latter (B) is in the final experimental stages and will be drafted and submitted for publication.
Peptide-based MOFs. A reticular family of novel 2D layered peptide based MOFs (7) is isolated varying the length of the pillar ligand used. Initially, 1D chains based on metal and peptide were synthesized and then the pillaring of the chains led to generation of 2D porous peptide based MOFs. The use of a small pillar ligand (bipyridyl) gave rise to a framework with pore size of 7 Å, whereas the largest ligand (bpeb) resulted in a MOF with the same topology but with pore size of 19 Å. This characteristic has a direct influence of the porosity and the BET surface area, increasing with the relative increase of the pillar ligand. This family of MOFs is very attractive due to their enhanced chemical and thermal stability, which is thought to be due to the strong H-interactions between the peptides. Racemic chiral molecules with different sizes and functionalities were loaded within all MOFs, and using GC-MS spectroscopy it was possible to separate the enantiomers. The peptide based MOF with the highest BET surface area and large pore size was used to separate the racemic mixture of the drug of ibuprofen as the enantiopure is the S-ibuprofen. These results present a new way to separate racemic drugs in which their enantiopurity is a key factor for their activity. This work is still in progress.
Polyamino acid based MOFs. The strategic design and synthesis of two chiral R- and S-tri-(aspartic acid) ligands and their subsequent use - varying the ratio between them, with Cu(II) under identical conditions has led to the formation of two isostructural and homochiral MOFs with opposite optical activity and a racemic network. For the first time, we have demonstrated that the enantioputity of the ligand used in the synthesis of MOFs is of high importance as it is the driving force for the structural topology of the MOF and consequently affecting their final properties. This work is drafted and submitted for publication.
During the 2 years of the fellowship, the fellow is represented as a co-author within three paper of high importance and advanced nanotechnological work based on the crystallization of MOFs on substrates using microfluidic pen lithography (Nature Communications, 2013), strategies to generate hollow superstructures (Chemistry – A European Chemisty, 2014) and finally dealing with CO2 capture (Crystal Growth and Design, 2014). The latter publication was the result of a collaboration with scientists from Tarbiat Modares University, Iran. Furthermore, a book chapter has been also accepted for publication in Wiley books 2014, giving an overview about the synthetic methodologies available for the isolation of nanoscale MOFs and their potential applications. He has also participated in five international conferences (2 poster and 3 oral presentations), where he has presented his results and interacted with scientists from other disciplines. In addition, the successful application for accessing Synchrotron facilities in Didcot, Oxford UK allowed him to collect data on samples that was not able to characterize using in house single crystal diffractometer; the obtained results are also presented in the Diamond Light Source 2013/14 Annual Review as a mini review.
One of the key role of the fellow within the NANOUP group is to acquire the very important and valuable experience through the supervision of projects and mentoring and tutoring master and postgraduate level students. The fellow has mentored 4 summer students, mentor a PhD student in collaboration with another institute ICMAB (Barcelona), and is also currently co-supervising the Thesis of a PhD student – Mr. Iván Burneo. In addition, he is also helping other group members with their projects and is involved in different projects as for example with scientists from Autonomous University of Madrid, Madrid.
In summary, the Marie Curie fellowship has been extremely productive and useful for his career and this is actually reflected by the interview invitations that he got as a junior group leader at the Jacobs University in Bremen, Germany and Ecole Polytecnique Federale Lausanne, Switzerland. While the 2 years of the fellowship were very beneficial in gaining of important scientific knowledge (dissemination of results, preparation of proposals for funding etc) and acquiring important qualities for the supervision of students, there is still some experimental work that needs to be completed and drafted for publication.