abstract
Iron(II) cyclopentadienyl carbonyl complexes are promising as CO-releasing molecules (CORMs) for therapeutic applications. In common with other metallodrugs, the practical application of Fe-CORMs may require their conjugation with biocompatible carriers to improve their bioavailability and protect them from premature degradation. Here, we show that the CO-releasing properties of the complexes [CpFe(CO)2Cl] (1) and [CpFe(CO)2CH2CONH2] (2) are retained when noncovalently encapsulated within cucurbit[7]uril (CB7), a well-established drug-enhancing excipient. The inclusion compounds were characterized in the solid-state by single-crystal and powder XRD, ATR-IR spectroscopy, Raman spectroscopy, TGA, and 13C{1H} CP MAS NMR. In the crystal structure of 2@CB7, there are two crystallographically independent [2@CB7] binary complexes that differ in the orientation of the guest molecules inside the CB cavity. High-resolution ESI-MS and 1H NMR studies verified the formation and stability of 1:1 2@CB7 inclusion complexes in an aqueous solution. In a physiological buffer, complex 2 is stable in the dark, but releases ca. 1.4 equiv of CO when irradiated with low-power cold white light, with a half-life (t 1/2) of 19.2 +/- 1.9 min. The photodecarbonylation behavior of the complexes is largely maintained in the inclusion compounds, with t 1/2 of 10.0 +/- 0.6 and 21.1 +/- 1.9 min for encapsulated 1 and 2.
keywords
CARBON-MONOXIDE RELEASE; INCLUSION COMPLEXES; PHOTOCHEMISTRY; ENCAPSULATION; CYCLODEXTRIN; DERIVATIVES; FERROCENE; DELIVERY; CYTOTOXICITY; CUCURBITURIL
subject category
Chemistry
authors
Monteiro, RP; Calhau, IB; Gomes, AC; Mendes, RF; Paz, FAA; Lopes, AD; Da Silva, JP; Romao, CC; Gonçalves, IS; Pillinger, M
our authors
Ana Catarina Costa Gomes Alves
Assistant Researcher
Filipe Alexandre Almeida Paz
Principal Researcher
Isabel Maria de Sousa Gonçalves
Associate Professor
Martyn Pillinger
Principal Researcher
Ricardo Faria Mendes
Junior ResearcherProjects
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)
acknowledgements
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials (UIDB/50011/2020 (DOI: 10.54499/UIDB/50011/2020), UIDP/50011/2020 (DOI: 10.54499/UIDP/50011/2020) and LA/P/0006/2020 (DOI: 10.54499/LA/P/0006/2020)), financed by national funds through the FCT (Fundacao para a Ciencia e a Tecnologia - Foundation for Science and Technology)/MCTES (Ministerio da Ciencia, Tecnologia e Ensino Superior) (PIDDAC). This study received Portuguese national funds from the FCT through project UIDB/04326/2020 (DOI: 10.54499/UIDB/04326/2020), UIDP/04326/2020 (DOI: 10.54499/UIDP/04326/2020) and LA/P/0101/2020 (DOI: 10.54499/LA/P/0101/2020), and from the operational programmes CRESC Algarve 2020 and COMPETE 2020 through project EMBRC.PT ALG-01-0145-FEDER-022121. R.P.M. (ref 2020.04758.BD, DOI: 10.54499/2020.04758.BD) and I.B.C. (ref 2021.05953.BD, DOI: 10.54499/2021.05953.BD) are grateful to the FCT and the European Social Fund (ESF) for Ph.D. grants. A. C. G. (CEECIND/02128/2017, DOI: 10.54499/CEECIND/02128/2017/CP1459/CT0039) and R. F. M. (CEECIND/00553/2017; DOI: 10.54499/CEECIND/00553/2017/CP1459/CT0034) thank the FCT/MCTES for research positions funded through the Individual Call to Scientific Employment Stimulus. The NMR spectrometers used in this work are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No. 022161 (cofinanced by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC; ref POCI-01-0145-FEDER-022161).