Beyond Solvent Exclusion: i-Motif Detecting Capability and an Alternative DNA Light-Switching Mechanism in a Ruthenium(II) Polypyridyl Complex

Spence, Philip; Fielden, John; Waller, Zoë A. E.

doi:10.1021/jacs.0c04789

“…Much attention has been paid to explore the interaction between the cationic porphyrins and nucleic acids because of the promising properties of the porphyrins in medical and biological applications. 2 , 3 , 5 - 7 , 9 - 17 , 41 - 51 The potential uses of the porphyrins in medical and biological fields are due to their anticancer, 11 , 13 , 17 antiviral and/or antibacterial/anti-inflammatory 4 , 6 , 10 , 14 - 16 and antifungal 6 , 52 activities. Porphyrins are also being used as imaging agents in medical imaging systems.…”

Section: Introductionmentioning

confidence: 99%

Kinetics and mechanism of formation of nickel(II)porphyrin and its interaction with DNA in aqueous medium

Habib

¹

,

Serniabad

²

,

Khan

³

et al. 2021

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Graphic abstract Kinetics between 5,10,15,20-tetrakis(N-methylpyridium-4-yl)porphyrin and Ni 2+ species were investigated in aqueous solution at 25 ±1 °C in I = 0.10 M (NaNO 3 ). Speciation of Ni 2+ was done in I = 0.10 M (NaNO 3 ) for knowing distribution of Ni 2+ species with solution pH. Experimental data were compared with speciation diagram constructed from the values of hydrolysis constants of Ni 2+ ion. Speciation data showed that hexaaquanickel(II) ions took place in hydrolysis reactions through formation of [Ni(OH 2 ) 6-n (OH) n ] 2-n species with solution pH. According to speciation of Ni 2+ and pH dependent rate constants, rate expression can be written as: d[Ni(TMPyP) 4+ ]/dt = ( k 1 [Ni 2+ (aq) ] + k 2 [Ni(OH) + (aq) ] + k 3 [Ni(OH) 2 o (aq) ] + k 4 [Ni(OH) 3 - (aq) ])[H 2 TMPyP 4+ ], where k 1 , k 2 , k 3 and k 4 were found to be k 1 = (0.62 ± 0.22) × 10 -2 ; k 2 = (3.60 ± 0.40) × 10 -2 ; k 3 = (2.09 ± 0.52) × 10 -2 , k 4 = (0.53 ± 0.04) × 10 -2 M -1 s -1 at 25 ±1 °C, respectively. Formation of hydrogen bonding between [Ni(H 2 O) 5 (OH)] + and [H 2 TMPyP] 4+ causes enhanced reactivity. Rate of formation of [Ni(II)TMPyP] 4+ complex was to be 3.99 × 10 -2 M -1 s -1 in I = 0.10 M, NaNO 3 (25 ± 1 °C). UV-Vis and fluorescence data suggested that [Ni(II)TMPyP] 4+ and [H 2 (TMPyP)] 4+ interact with DNA via outside binding with self-stacking and intercalation, respectively. SYNOPSIS Kinetics of tetrakis(1-methylpyridium-4-yl)porphyrin with Ni 2+ were studied in aqueous medium at 25 ±1 °C in ...

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“…Given the results observed using gel electrophoresis we were interested in the relative binding affinity of the complexes to DS DNA. We performed a fluorescence intercalator displacement (FID) assay to determine the displacement of thiazole orange (TO) in the presence of the complexes [38,39] …”

Section: Resultsmentioning

confidence: 99%

“…We performed a fluorescence intercalator displacement (FID) assay to determine the displacement of thiazole orange (TO) in the presence of the complexes. [ 38 , 39 ]…”

Section: Resultsmentioning

confidence: 99%

Understanding the Potential In Vitro Modes of Action of Bis(β‐diketonato) Oxovanadium(IV) Complexes

Sergi

¹

,

Bulut

²

,

Xia

³

et al. 2021

Self Cite

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To understand the potential in vitro modes of action of bis(β‐diketonato) oxovanadium(IV) complexes, nine compounds of varying functionality have been screened using a range of biological techniques. The antiproliferative activity against a range of cancerous and normal cell lines has been determined, and show these complexes are particularly sensitive against the lung carcinoma cell line, A549. Annexin V (apoptosis) and Caspase‐3/7 assays were studied to confirm these complexes induce programmed cell death. While gel electrophoresis was used to determine DNA cleavage activity and production of reactive oxygen species (ROS), the Comet assay was used to determine induced genomic DNA damage. Additionally, Förster resonance energy transfer (FRET)‐based DNA melting and fluorescent intercalation displacement assays have been used to determine the interaction of the complexes with double strand (DS) DNA and to establish preferential DNA base‐pair binding (AT versus GC).

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“… 22 Since the i-motif structure is stabilized by the formation of hydrogen bonds between protonated cytosine and non-protonated cytosine, its spatial structure is greatly affected by the pH value. 23 The i-motif structure is mostly formed and stabilized under acidic conditions but not under neutral or alkaline conditions. Thus, the i-motif has been extensively used in DNA nanotechnology for molecular sensing and therapeutic applications.…”

Section: Introductionmentioning

confidence: 99%

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

Zhang¹,

Wang²,

Zhu³

et al. 2021

IJN

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Background: GD2 is a mainstream biomarker for neuroblastoma (NB)-targeted therapy. Current anti-GD2 therapeutics exhibit several side effects since GD2 is also expressed at low levels on normal cells. Thus, current anti-GD2 therapeutics can be compromised by the coexistence of the target receptor on both cancer cells and normal cells. Propose: Aptamers are promising and invaluable molecular tools. Because of the pH difference between tumor and normal cells, in this study, we constructed a pH-sensitive aptamer-mediated drug delivery system (IGD-Targeted). Methods: In vivo Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was used to generate a novel GD2 aptamer. Flow cytometry and molecular docking were applied to assess the binding specificities, affinities abilities of the aptamers. Confocal microscope, CCK8 assay, and BrdU assay were utilized to evaluate whether IGD-Targeted could only bind with GD2 at acidic environment. To evaluate whether IGD-Targeted could inhibit GD2-positive tumor and protect normal cells, in vivo living imaging, histomorphological staining, blood test, and RNA-sequencing were observed in animal model. Results: GD2 aptamer termed as DB67 could bind with GD2-positive cells with high specificity, while has minimal cross-reactivities to other negative cells. It has been validated that the i-motif in IGD-Targeted facilitates the binding specificity and affinity of the GD2 aptamer to GD2-positive NB tumor cells but does not interfere with GD2-positive normal cells at the pH of the cellular microenvironment. In addition, IGD-Targeted is capable of delivering Dox to only GD2-positive NB tumor cells and not to normal cells in vivo and in vitro, resulting in precise inhibition of tumor cells and protection of normal cells. Conclusion:This study suggests that IGD-Targeted as a promising platform for NB therapy which could show greater tumor inhibition and fewer side effects to normal cells, regardless of the existence of the same receptor on the target and nontarget cells.

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Beyond Solvent Exclusion: i-Motif Detecting Capability and an Alternative DNA Light-Switching Mechanism in a Ruthenium(II) Polypyridyl Complex

Cited by 28 publications

References 68 publications

Kinetics and mechanism of formation of nickel(II)porphyrin and its interaction with DNA in aqueous medium

Kinetics and mechanism of formation of nickel(II)porphyrin and its interaction with DNA in aqueous medium

Understanding the Potential In Vitro Modes of Action of Bis(β‐diketonato) Oxovanadium(IV) Complexes

A Novel pH-Sensitive Multifunctional DNA Nanomedicine: An Enhanced and Harmless GD2 Aptamer-Mediated Strategy for Guiding Neuroblastoma Antitumor Therapy

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