Synthesis, photophysical characterization, relaxometric studies and molecular docking studies of gadolinium-free contrast agents for dual modal imaging
Three new EDTA-N, N’’ Bis(amides) ligands functionalized by luminophores (4-(aminomethyl)pyridine (L1) and 2-aminoanthraquinone (L2) and sulphonate (aminomethanesulfonic acid (L3)) on the amide side-arms (L1-L3) and their transition metal complexes (Mn (II), Cu (II) (except for L3), Zn (II)) were sy...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715622000261 |
| _version_ | 1811178153485271040 |
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| author | CuhaWijay Sathiyajith Andrew J. Hallett Peter G. Edwards |
| author_facet | CuhaWijay Sathiyajith Andrew J. Hallett Peter G. Edwards |
| author_sort | CuhaWijay Sathiyajith |
| collection | DOAJ |
| description | Three new EDTA-N, N’’ Bis(amides) ligands functionalized by luminophores (4-(aminomethyl)pyridine (L1) and 2-aminoanthraquinone (L2) and sulphonate (aminomethanesulfonic acid (L3)) on the amide side-arms (L1-L3) and their transition metal complexes (Mn (II), Cu (II) (except for L3), Zn (II)) were synthesized and characterized by analytical and spectroscopic techniques. The potential of L1-L3 to act as a dual-modal contrast agent for magnetic resonance imaging (MRI CA) was evaluated by measuring physicochemical properties such as (a) thermodynamic stability by measuring macroscopic protonation constants and stability constants with potentiometric titrations (b) R1 relaxivities by NMR relaxivity studies (c) spectrophotometric investigations. Comparative studies revealed Mn-L1 has performance comparable to the commercially available gadolinium-based contrast agents Magnevist® and Dotarem®. It is also higher than Teslascan® (manganese-based contrast agent, previously clinically approved and withdrawn from the market). Specifically, Mn-L1 exhibited relaxivity of 3.52 mM-1S-1 (at 30 MHz, 37 °C) as opposed to Teslascan® of 1.88 mM-1s−1(at 20 MHz, 37 °C). L1 also exhibited high overall stability constant for its Zn (II) complex (16.03), slightly higher than Teslascan® (15.1). Furthermore, the sharp break exhibited in the NMRD titration profile of L1 with Mn (II) indicated a 1:1 complex formation and substantiates a higher association constant. The photophysical characterization confirmed the ability of L1 and L2 to act as on–off type, fluorescent-based chemosensors for Cu (II). Time-resolved fluorescence investigations (TCSPC) indicated the potentiality of L1 for live-cell imaging. Unfortunately, while relaxivity studies on L2 were prevented by solubility issues at physiological pH, L3 exhibited poor complexation with Mn (II) and prevented further investigation. We also demonstrate through a structure-based virtual screening that L1 could act as a multi-target ligand to modulate the activity of two unrelated receptor proteins; Human aurora B kinase and Human serum albumin. Moreover, L1 exhibited a strong binding affinity for blood plasma protein, human serum albumin and this was relatively higher than FODIPIR, the ligand for Teslascan®. |
| first_indexed | 2024-04-11T06:13:36Z |
| format | Article |
| id | doaj.art-ec2c971569a9405e82e8b5cb92d7355f |
| institution | Directory Open Access Journal |
| issn | 2211-7156 |
| language | English |
| last_indexed | 2024-04-11T06:13:36Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj.art-ec2c971569a9405e82e8b5cb92d7355f2022-12-22T04:41:08ZengElsevierResults in Chemistry2211-71562022-01-014100307Synthesis, photophysical characterization, relaxometric studies and molecular docking studies of gadolinium-free contrast agents for dual modal imagingCuhaWijay Sathiyajith0Andrew J. Hallett1Peter G. Edwards2Corresponding author.; School of Chemistry, Cardiff University, Main Building, Park Place, CF10 3AT, Cardiff, UKSchool of Chemistry, Cardiff University, Main Building, Park Place, CF10 3AT, Cardiff, UKSchool of Chemistry, Cardiff University, Main Building, Park Place, CF10 3AT, Cardiff, UKThree new EDTA-N, N’’ Bis(amides) ligands functionalized by luminophores (4-(aminomethyl)pyridine (L1) and 2-aminoanthraquinone (L2) and sulphonate (aminomethanesulfonic acid (L3)) on the amide side-arms (L1-L3) and their transition metal complexes (Mn (II), Cu (II) (except for L3), Zn (II)) were synthesized and characterized by analytical and spectroscopic techniques. The potential of L1-L3 to act as a dual-modal contrast agent for magnetic resonance imaging (MRI CA) was evaluated by measuring physicochemical properties such as (a) thermodynamic stability by measuring macroscopic protonation constants and stability constants with potentiometric titrations (b) R1 relaxivities by NMR relaxivity studies (c) spectrophotometric investigations. Comparative studies revealed Mn-L1 has performance comparable to the commercially available gadolinium-based contrast agents Magnevist® and Dotarem®. It is also higher than Teslascan® (manganese-based contrast agent, previously clinically approved and withdrawn from the market). Specifically, Mn-L1 exhibited relaxivity of 3.52 mM-1S-1 (at 30 MHz, 37 °C) as opposed to Teslascan® of 1.88 mM-1s−1(at 20 MHz, 37 °C). L1 also exhibited high overall stability constant for its Zn (II) complex (16.03), slightly higher than Teslascan® (15.1). Furthermore, the sharp break exhibited in the NMRD titration profile of L1 with Mn (II) indicated a 1:1 complex formation and substantiates a higher association constant. The photophysical characterization confirmed the ability of L1 and L2 to act as on–off type, fluorescent-based chemosensors for Cu (II). Time-resolved fluorescence investigations (TCSPC) indicated the potentiality of L1 for live-cell imaging. Unfortunately, while relaxivity studies on L2 were prevented by solubility issues at physiological pH, L3 exhibited poor complexation with Mn (II) and prevented further investigation. We also demonstrate through a structure-based virtual screening that L1 could act as a multi-target ligand to modulate the activity of two unrelated receptor proteins; Human aurora B kinase and Human serum albumin. Moreover, L1 exhibited a strong binding affinity for blood plasma protein, human serum albumin and this was relatively higher than FODIPIR, the ligand for Teslascan®.http://www.sciencedirect.com/science/article/pii/S2211715622000261Non-GadoliniumManganeseLuminescenceMRI/OITheragnostic agents |
| spellingShingle | CuhaWijay Sathiyajith Andrew J. Hallett Peter G. Edwards Synthesis, photophysical characterization, relaxometric studies and molecular docking studies of gadolinium-free contrast agents for dual modal imaging Results in Chemistry Non-Gadolinium Manganese Luminescence MRI/OI Theragnostic agents |
| title | Synthesis, photophysical characterization, relaxometric studies and molecular docking studies of gadolinium-free contrast agents for dual modal imaging |
| title_full | Synthesis, photophysical characterization, relaxometric studies and molecular docking studies of gadolinium-free contrast agents for dual modal imaging |
| title_fullStr | Synthesis, photophysical characterization, relaxometric studies and molecular docking studies of gadolinium-free contrast agents for dual modal imaging |
| title_full_unstemmed | Synthesis, photophysical characterization, relaxometric studies and molecular docking studies of gadolinium-free contrast agents for dual modal imaging |
| title_short | Synthesis, photophysical characterization, relaxometric studies and molecular docking studies of gadolinium-free contrast agents for dual modal imaging |
| title_sort | synthesis photophysical characterization relaxometric studies and molecular docking studies of gadolinium free contrast agents for dual modal imaging |
| topic | Non-Gadolinium Manganese Luminescence MRI/OI Theragnostic agents |
| url | http://www.sciencedirect.com/science/article/pii/S2211715622000261 |
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