Molecules

Research

12 pages, 2312 KiB

Open AccessArticle

An Activatable T₁-Weighted MR Contrast Agent: A Noninvasive Tool for Tracking the Vicinal Thiol Motif of Thioredoxin in Live Cells

by Jongeun Kang, Eunha Hwang, Hyunseung Lee, Mi Young Cho, Sanu Karan, Hak Nam Kim, Jong Seung Kim, Jonathan L. Sessler, Sankarprasad Bhuniya and Kwan Soo Hong

Molecules 2021, 26(7), 2018; https://doi.org/10.3390/molecules26072018 - 01 Apr 2021

Cited by 1 | Viewed by 1876

Abstract

We have synthesized new magnetic resonance imaging (MRI) T₁ contrast agents (CA1 and CA2) that permit the activatable recognition of the cellular vicinal thiol motifs of the protein thioredoxin. The contrast agents showed MR relaxivities typical of gadolinium complexes with a single [...] Read more.

We have synthesized new magnetic resonance imaging (MRI) T₁ contrast agents (CA1 and CA2) that permit the activatable recognition of the cellular vicinal thiol motifs of the protein thioredoxin. The contrast agents showed MR relaxivities typical of gadolinium complexes with a single water molecule coordinated to a Gd³⁺ center (i.e., ~4.54 mM⁻¹s⁻¹) for both CA1 and CA2 at 60 MHz. The contrast agent CA1 showed a ~140% relaxivity enhancement in the presence of thioredoxin, a finding attributed to a reduction in the flexibility of the molecule after binding to thioredoxin. Support for this rationale, as opposed to one based on preferential binding, came from ¹H-¹⁵N-HSQC NMR spectral studies; these revealed that the binding affinities toward thioredoxin were almost the same for both CA1 and CA2. In the case of CA1, T₁-weighted phantom images of cancer cells (MCF-7, A549) could be generated based on the expression of thioredoxin. We further confirmed thioredoxin expression-dependent changes in the T₁-weighted contrast via knockdown of the expression of the thioredoxin using siRNA-transfected MCF-7 cells. The nontoxic nature of CA1, coupled with its relaxivity features, leads us to suggest that it constitutes a first-in-class MRI T₁ contrast agent that allows for the facile and noninvasive monitoring of vicinal thiol protein motif expression in live cells. Full article

(This article belongs to the Special Issue Supramolecular Anion Binding and Molecular Recognition)

► Show Figures

Graphical abstract

13 pages, 2939 KiB

Open AccessArticle

Solvent-Controlled Self-Assembled Oligopyrrolic Receptor

by Fei Wang, Kejiang Liang, Mads Christian Larsen, Steffen Bähring, Masatoshi Ishida, Hiroyuki Furuta and Atanu Jana

Molecules 2021, 26(6), 1771; https://doi.org/10.3390/molecules26061771 - 22 Mar 2021

Cited by 3 | Viewed by 2450

Abstract

We report a fully organic pyridine-tetrapyrrolic U-shaped acyclic receptor 10, which prefers a supramolecular pseudo-macrocyclic dimeric structure (10)₂ in a less polar, non-coordinating solvent (e.g., CHCl₃). Conversely, when it is crystalized from a polar, coordinating solvent (e.g., [...] Read more.

We report a fully organic pyridine-tetrapyrrolic U-shaped acyclic receptor 10, which prefers a supramolecular pseudo-macrocyclic dimeric structure (10)₂ in a less polar, non-coordinating solvent (e.g., CHCl₃). Conversely, when it is crystalized from a polar, coordinating solvent (e.g., N,N-dimethylformamide, DMF), it exhibited an infinite supramolecular one-dimensional (1D) “zig-zag” polymeric chain, as inferred from the single-crystal X-ray structures. This supramolecular system acts as a potential receptor for strong acids, e.g., p-toluenesulfonic acid (PTSA), methane sulfonic acid (MSA), H₂SO₄, HNO₃, and HCl, with a prominent colorimetric response from pale yellow to deep red. The receptor can easily be recovered from the organic solution of the host–guest complex by simple aqueous washing. It was observed that relatively stronger acids with pK_a < −1.92 in water were able to interact with the receptor, as inferred from ¹H NMR titration in tetrahydrofuran-d₈ (THF-d₈) and ultraviolet–visible (UV–vis) spectroscopic titrations in anhydrous THF at 298 K. Therefore, this new dynamic supramolecular receptor system may have potentiality in materials science research. Full article

(This article belongs to the Special Issue Supramolecular Anion Binding and Molecular Recognition)

► Show Figures

Graphical abstract

10 pages, 1405 KiB

Open AccessArticle

Ratiometric Fluorescence Assay for Nitroreductase Activity: Locked-Flavylium Fluorophore as a NTR-Sensitive Molecular Probe

by Su Jung Kim, Jung Won Yoon, Shin A Yoon and Min Hee Lee

Molecules 2021, 26(4), 1088; https://doi.org/10.3390/molecules26041088 - 19 Feb 2021

Cited by 12 | Viewed by 3040

Abstract

Nitroreductases belong to a member of flavin-containing enzymes that can reduce nitroaromatic compounds to amino derivatives with NADH as an electron donor. NTR activity is known to be elevated in the cancerous environment and is considered an advantageous target in therapeutic prodrugs for [...] Read more.

Nitroreductases belong to a member of flavin-containing enzymes that can reduce nitroaromatic compounds to amino derivatives with NADH as an electron donor. NTR activity is known to be elevated in the cancerous environment and is considered an advantageous target in therapeutic prodrugs for the treatment of cancer. Here, we developed a ratiometric fluorescent molecule for observing NTR activity in living cells. This can provide a selective and sensitive response to NTR with a distinct increase in fluorescence ratio (FI₅₃₀/FI₆₃₀) as well as color changes. We also found a significant increase in NTR activity in cervical cancer HeLa and lung cancer A549 cells compared to non-cancerous NIH3T3. We proposed that this new ratiometric fluorescent molecule could potentially be used as a NTR-sensitive molecular probe in the field of cancer diagnosis and treatment development related to NTR activity. Full article

(This article belongs to the Special Issue Supramolecular Anion Binding and Molecular Recognition)

► Show Figures

Graphical abstract

8 pages, 2140 KiB

Open AccessArticle

Post Synthetic Modification of Planar Antiaromatic Hexaphyrin (1.0.1.0.1.0) by Regio-Selective, Sequential S_NAr

by Ranjan Dutta, Brijesh Chandra, Seong-Jin Hong, Yeonju Park, Young Mee Jung and Chang-Hee Lee

Molecules 2021, 26(4), 1025; https://doi.org/10.3390/molecules26041025 - 15 Feb 2021

Cited by 2 | Viewed by 1996

Abstract

In spite of unique structural, spectroscopic and redox properties, the synthetic variants of the planar, antiaromatic hexaphyrin (1.0.1.0.1.0) derivatives 2, has been limited due to the low yields and difficulty in access to the starting material. A chemical modification of the meso [...] Read more.

In spite of unique structural, spectroscopic and redox properties, the synthetic variants of the planar, antiaromatic hexaphyrin (1.0.1.0.1.0) derivatives 2, has been limited due to the low yields and difficulty in access to the starting material. A chemical modification of the meso-substituents could be good alternative overcoming the synthetic barrier. Herein, we report a regio-selective nucleophilic aromatic substitution (S_NAr) of meso-pentafluorophenyl group in rosarrin 2 with catechol. The reaction afforded benzodioxane fused rosarrin 3 as single product with high yield. The intrinsic antiaromatic character of the starting rosarrin 2 retained throughout the reactions. Clean, two electron reduction was achieved by treatment of 3 with SnCl₂•2H₂O affording 26π-electron aromatic rosarrin 4. The synthesized compounds exhibited noticeable changes in photophysical and redox properties compared with starting rosarrin 2. Full article

(This article belongs to the Special Issue Supramolecular Anion Binding and Molecular Recognition)

► Show Figures

Graphical abstract

10 pages, 1929 KiB

Open AccessCommunication

Binding and Sensing Properties of a Hybrid Naphthalimide–Pyrene Aza-Cyclophane towards Nucleotides in an Aqueous Solution

by Aleksandr M. Agafontsev, Aleksandr S. Oshchepkov, Tatiana A. Shumilova and Evgeny A. Kataev

Molecules 2021, 26(4), 980; https://doi.org/10.3390/molecules26040980 - 12 Feb 2021

Cited by 6 | Viewed by 2400

Abstract

Selective recognition of nucleotides with synthetic receptors is an emerging direction to solve a series of nucleic acid-related challenges in biochemistry. Towards this goal, a new aza-cyclophane with two different dyes, naphthalimide and pyrene, connected through a triamine linker has been synthesized and [...] Read more.

Selective recognition of nucleotides with synthetic receptors is an emerging direction to solve a series of nucleic acid-related challenges in biochemistry. Towards this goal, a new aza-cyclophane with two different dyes, naphthalimide and pyrene, connected through a triamine linker has been synthesized and studied for the ability to bind and detect nucleoside triphosphates in an aqueous solution. The receptor shows Foerster resonance energy transfer (FRET) in fluorescence spectra upon excitation in DMSO, which is diminished dramatically in the presence of water. According to binding studies, the receptor has a preference to bind ATP (adenosine triphosphate) and CTP (cytidine triphosphate) with a “turn-on” fluorescence response. Two separate emission bands of dyes allow one to detect nucleotides in a ratiometric manner in a broad concentration range of 10⁻⁵–10⁻³ M. Spectroscopic measurements and quantum chemical calculations suggest the formation of receptor–nucleotide complexes, which are stabilized by dispersion interactions between a nucleobase and dyes, while hydrogen bonding interactions of nucleobases with the amine linkers are responsible for selectivity. Full article

(This article belongs to the Special Issue Supramolecular Anion Binding and Molecular Recognition)

► Show Figures

Graphical abstract

9 pages, 2951 KiB

Open AccessArticle

Tuned Cd²⁺ Selectivity: Showcase of Electronic and Regio-Effect of π-Extended Di-2-Picolylamine-Substituted Quinoline-Based Tolans

by Min-Sung Ko, P. Sankara Rao and Dong-Gyu Cho

Molecules 2021, 26(4), 917; https://doi.org/10.3390/molecules26040917 - 09 Feb 2021

Viewed by 1796

Abstract

π-Extended di-2-picolylamine (DPA)-substituted 8-hydroxyquinoline (8-HQ) tolans (2) were synthesized for testing electronic and regio-effects. The electron-poor CN-tolan (2b) showed clear selectivity for Cd²⁺ (>>Zn²⁺) over other metal ions via turn-on fluorescence, while the electron-rich MeO-tolan ( [...] Read more.

π-Extended di-2-picolylamine (DPA)-substituted 8-hydroxyquinoline (8-HQ) tolans (2) were synthesized for testing electronic and regio-effects. The electron-poor CN-tolan (2b) showed clear selectivity for Cd²⁺ (>>Zn²⁺) over other metal ions via turn-on fluorescence, while the electron-rich MeO-tolan (2a) displayed no clear metal selectivity. Furthermore, considering that there was no significant energy difference between the Cd²⁺ complexes of 1 and 2b, the intended regio-effect (7- vs. 5-substituted effect) did not induce steric hindrance. Thus, the regio-effect is mainly electronic. Considering the above, 2a and 2b constitute a complete showcase in which electronic and regio-effects modulate the metal selectivity. The fluorescence titration of 2b (10 mM) with Cd²⁺ showed that the limit of detection (LOD) of the Cd²⁺-selective 2b was 158 nM in PBS (phosphate-buffered saline) (10 mM, pH 7.2) containing 50% MeOH. Full article

(This article belongs to the Special Issue Supramolecular Anion Binding and Molecular Recognition)

► Show Figures

Graphical abstract

9 pages, 3577 KiB

Open AccessCommunication

Design and Synthesis of π-Extended Resveratrol Analogues and In Vitro Antioxidant and Anti-Inflammatory Activity Evaluation

by Ki Yoon Nam, Kongara Damodar, Yeontaek Lee, Lee Seul Park, Ji Geun Gim, Jae Phil Park, Seong Ho Jeon and Jeong Tae Lee

Molecules 2021, 26(3), 646; https://doi.org/10.3390/molecules26030646 - 26 Jan 2021

Cited by 6 | Viewed by 2658

Abstract

The research on resveratrol (1) has been conducted intensively over a long time due to its proven antioxidant activity and disease-fighting capabilities. Many efforts have also been made to increase these biological effects. In the present study, six new extended aromatic [...] Read more.

The research on resveratrol (1) has been conducted intensively over a long time due to its proven antioxidant activity and disease-fighting capabilities. Many efforts have also been made to increase these biological effects. In the present study, six new extended aromatic resveratrol analogues containing naphthalene (2) and its bioisosteres quinoline (3 and 4), isoquinoline (5) quinoxaline (6) and quinazoline (7) scaffolds were designed and synthesized using an annulation strategy. The antioxidant and anti-inflammatory activities of these compounds were investigated. All compounds showed better antioxidant activity than resveratrol in ABTS assay. As for the anti-inflammatory test, 5 and 7 exhibited better activity than resveratrol. It is worth noting that nitrogen substitution on the extended aromatic resveratrol analogues has a significant impact on cell viability. Taking the antioxidant activities and NO inhibition activities into consideration, we conclude that isoquinoline analogue 5 may qualify for the further investigation of antioxidant and anti-inflammatory therapy. Furthermore, our study results suggest that in order to improve the biological activity of polyphenolic compounds, extended aromaticity and nitrogen substitution strategy could be a viable method for the design of future drug candidates. Full article

(This article belongs to the Special Issue Supramolecular Anion Binding and Molecular Recognition)

► Show Figures

Figure 1

12 pages, 4696 KiB

Open AccessCommunication

Nitro-Substituted Dipyrrolyldiketone BF₂ Complexes as Electronic-State-Adjustable Anion-Responsive π-Electronic Systems

by Atsuko Kuno and Hiromitsu Maeda

Molecules 2021, 26(3), 595; https://doi.org/10.3390/molecules26030595 - 23 Jan 2021

Cited by 1 | Viewed by 2351

Abstract

Nitro-substituted π-electronic molecules are fascinating because of their unique electronic and optical properties and the ease of their transformation into various functional derivatives. Herein, nitro-introduced dipyrrolyldiketone BF₂ complexes as anion-responsive π-electronic molecules were synthesized, and their electronic properties and anion-binding abilities were [...] Read more.

Nitro-substituted π-electronic molecules are fascinating because of their unique electronic and optical properties and the ease of their transformation into various functional derivatives. Herein, nitro-introduced dipyrrolyldiketone BF₂ complexes as anion-responsive π-electronic molecules were synthesized, and their electronic properties and anion-binding abilities were investigated by spectroscopic analyses and theoretical studies. The obtained nitro-substituted derivatives showed solvent-dependent UV/vis spectral changes and high anion-binding affinities due to the easily pyrrole-inverted conformations and polarized pyrrole NH sites upon the introduction of electron-withdrawing moieties. Full article

(This article belongs to the Special Issue Supramolecular Anion Binding and Molecular Recognition)

► Show Figures

Graphical abstract

17 pages, 1994 KiB

Open AccessArticle

Tetrapodal Anion Transporters

by Alexander M. Gilchrist, Lijun Chen, Xin Wu, William Lewis, Ethan N.W. Howe, Lauren K. Macreadie and Philip A. Gale

Molecules 2020, 25(21), 5179; https://doi.org/10.3390/molecules25215179 - 06 Nov 2020

Cited by 7 | Viewed by 3092

Abstract

Synthetic anion transporters that facilitate chloride transport are promising candidates for channelopathy treatments. However, most anion transporters exhibit an undesired side effect of facilitating proton transport via interacting with fatty acids present in the membrane. To address the limitation, we here report the [...] Read more.

Synthetic anion transporters that facilitate chloride transport are promising candidates for channelopathy treatments. However, most anion transporters exhibit an undesired side effect of facilitating proton transport via interacting with fatty acids present in the membrane. To address the limitation, we here report the use of a new tetrapodal scaffold to maximize the selective interaction with spherical chloride over binding the carboxylate headgroup of fatty acids. One of the new transporters demonstrated a high selectivity for chloride uniport over fatty acid-induced proton transport while being >10 times more active in chloride uniport than strapped calixpyrroles that were previously the only class of compounds known to possess similar selectivity properties. Full article

(This article belongs to the Special Issue Supramolecular Anion Binding and Molecular Recognition)

► Show Figures