Most contemporary theories for the chemical origins of life include the prebiotic synthesis of informational polymers, including strong interpretations of the RNA World hypothesis. Existing challenges to the prebiotic emergence of RNA have encouraged exploration of the possibility that RNA was preceded by an ancestral informational polymer, or proto-RNA, that formed more easily on the early Earth. We have proposed that the proto-nucleobases of proto-RNA would have readily formed glycosides with ribose and that these proto-nucleosides would have formed base pairs as monomers in aqueous solution, two properties not exhibited by the extant nucleosides or nucleotides.
View Article and Find Full Text PDFA goal of supramolecular chemistry is to create covalent polymers of precise composition and stereochemistry from complex mixtures by the reversible assembly of specific monomers prior to covalent bond formation. We illustrate the power of this approach with short oligomers of deoxyadenosine monophosphate ((dA)3'p), ≥ 3, which form supramolecular assemblies with cyanuric acid. The addition of a condensing agent to these assemblies results in their selective, non-enzymatic polymerization to form long polymers (, (dA)3'p).
View Article and Find Full Text PDFThe mechanism by which informational polymers first formed on the early earth is currently unknown. The RNA world hypothesis implies that RNA oligomers were produced prebiotically, before the emergence of enzymes, but the demonstration of such a process remains challenging. Alternatively, RNA may have been preceded by an earlier ancestral polymer, or proto-RNA, that had a greater propensity for self-assembly than RNA, with the eventual transition to functionally superior RNA being the result of chemical or biological evolution.
View Article and Find Full Text PDFThe hypothesis that RNA and DNA are products of chemical and biological evolution has motivated our search for alternative nucleic acids that may have come earlier in the emergence of life-polymers that possess a proclivity for covalent and non-covalent self-assembly not exhibited by RNA. Our investigations have revealed a small set of candidate ancestral nucleobases that self-assemble into hexameric rosettes that stack in water to form long, twisted, rigid supramolecular polymers. These structures exhibit properties that provide robust solutions to long-standing problems that have stymied the search for a prebiotic synthesis of nucleic acids.
View Article and Find Full Text PDFAqueous solutions of equimolar mixtures of 2,4,6-triaminopyrimidine (TAP) and carboxylic acid substituted cyanuric acid (CyCo6 or 4MeCyCo6) monomers self-assemble into gel-forming supramolecular polymers. Macroscopic fibers drawn from these mixtures were analyzed by X-ray diffraction to determine their molecular structures. Computational methods were used to explore the intrinsic intermolecular interactions that contribute to the structure and stability of these assemblies.
View Article and Find Full Text PDFThe cyanuric acid (CA) heterocycle forms supramolecular structures with adenine nucleobases/nucleosides and oligonucleotides, leading to speculation that they can act as forerunners to RNA. Herein, the assembly behavior of RNA containing CA and CA-ribose nucleoside was studied. Contrary to previous reports, CA in RNA and the CA-ribonucleoside resulted in destabilization of supramolecular assemblies, which led to a reevaluation of the CA-adenine hexameric rosette structure.
View Article and Find Full Text PDFWidespread testing for the presence of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals remains vital for controlling the COVID-19 pandemic prior to the advent of an effective treatment. Challenges in testing can be traced to an initial shortage of supplies, expertise, and/or instrumentation necessary to detect the virus by quantitative RT-PCR (RT-qPCR), the most robust, sensitive, and specific assay currently available. Here we show that academic biochemistry and molecular biology laboratories equipped with appropriate expertise and infrastructure can replicate commercially available SARS-CoV-2 RT-qPCR test kits and backfill pipeline shortages.
View Article and Find Full Text PDFWidespread testing for the presence of the novel coronavirus SARS-CoV-2 in individuals remains vital for controlling the COVID-19 pandemic prior to the advent of an effective treatment. Challenges in testing can be traced to an initial shortage of supplies, expertise and/or instrumentation necessary to detect the virus by quantitative reverse transcription polymerase chain reaction (RT-qPCR), the most robust, sensitive, and specific assay currently available. Here we show that academic biochemistry and molecular biology laboratories equipped with appropriate expertise and infrastructure can replicate commercially available SARS-CoV-2 RT-qPCR test kits and backfill pipeline shortages.
View Article and Find Full Text PDFThe simple and reversible control of the degree of polymerization, and thereby the bulk material properties, of a supramolecular polymer is reported. Noncovalent capping agents (chain stoppers) modulate the length of supramolecular polymers by stacking on the surfaces of the polymer's ends. Methylene blue () is a positively charged, planar polycyclic dye that acts as a chain stopper.
View Article and Find Full Text PDFAqueous solutions of the achiral, monomeric, nucleobase mimics (2,4,6-triaminopyrimidine, TAP, and a cyanuric acid derivative, CyCo6) spontaneously assemble into macroscopic homochiral domains of supramolecular polymers. These assemblies exhibit a high degree of chiral amplification. Addition of a small quantity of one handedness of a chiral derivative of CyCo6 generates exclusively homochiral structures.
View Article and Find Full Text PDFWith the objective of developing efficient sensitizers for therapeutic applications, we synthesized a water-soluble 5,10,15,20-tetrakis(3,4-dihydroxyphenyl)chlorin (TDC) and investigated its in vitro and in vivo biological efficacy, comparing it with the commercially available sensitizers. TDC showed high water solubility (6-fold) when compared with that of Foscan and exhibited excellent triplet-excited-state (84%) and singlet-oxygen (80%) yields. In vitro photobiological investigations in human-ovarian-cancer cell lines SKOV-3 showed high photocytotoxicity, negligible dark toxicity, rapid cellular uptake, and specific localization of TDC in neoplastic cells as assessed by flow-cytometric cell-cycle and propidium iodide staining analysis.
View Article and Find Full Text PDFSynthesis, photophysical and metal ion recognition properties of a series of amino acid-linked free-base and Zn-porphyrin derivatives (5-9) are reported. These porphyrin derivatives showed favorable photophysical properties including high molar extinction coefficients (>1 × 10(5) m(-1) cm(-1) for the Soret band), quantum yields of triplet excited states (63-94%) and singlet oxygen generation efficiencies (59-91%). Particularly, the Zn-porphyrin derivatives, 6 and 9 showed higher molar extinction coefficients, decreased fluorescence quantum yields, and higher triplet and singlet oxygen quantum yields compared to the corresponding free-base porphyrin derivatives.
View Article and Find Full Text PDFNovel biomimetic mononuclear complexes, [Fe()Cl2](+) () and [Cu()(H2O)](2+) () based on naphthalimide appended tripodal tetradentate ligand ( = 2,2',2''-(3,3',3''-(2,2',2''-nitrilotris(methylene)tris(1H-benzo[d]imidazole-2,1-diyl))tris(propane-3,1-diyl))tris(1H-benzo-[de]isoquinoline-1,3(2H)-dione)) have been synthesized and characterized by various analytical and spectral techniques. In addition, the structures of the ligand () and complex were established unambiguously through X-ray crystal structure analysis. Uniquely, the coordination with a metal ion modified the ligand scaffold to interact efficiently with ct-DNA (groove binding) as well as protein (hydrophobic and/or electrostatic interactions).
View Article and Find Full Text PDFThe Gram-negative Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum are major causative agents of aggressive periodontal disease. Due to increase in the number of antibiotic-resistant bacteria, antimicrobial Photodynamic therapy (aPDT) seems to be a plausible alternative. In this work, photosensitization was performed on Gram-positive and Gram-negative bacteria in pure culture using new-age cationic porphyrins, namely mesoimidazolium-substituted porphyrin derivative (ImP) and pyridinium-substituted porphyrin derivative (PyP).
View Article and Find Full Text PDFWe have investigated the DNA binding interactions and in vitro photoactivated DNA damage induced by a neutral water soluble porphyrin derivative 5,10,15,20-tetrakis(2,4,6-trihydroxyphenyl)porphyrin (TTHPP) and its zinc derivative 5,10,15,20-tetrakis(2,4,6-trihydroxyphenyl)porphyrinato zinc(II) (Zn-TTHPP) upon visible light irradiation through various spectroscopic techniques and employing repair endonucleases. These porphyrin derivatives exhibited high affinity toward DNA through groove binding interactions as evidenced through the UV-vis absorption, emission, circular dichroism spectral and viscosity changes. Interestingly, the free base porphyrin derivative, TTHPP generated efficient singlet oxygen mediated DNA damage sensitive to formamidopyrimidine-DNA glycosylase (Fpg protein), when compared with its metal derivative and to the well-known photosensitizer, hematoporphyrin.
View Article and Find Full Text PDFWe synthesized a novel water-soluble porphyrin THPP and its metalated derivative Zn-THPP having excellent triplet excited state quantum yields and singlet oxygen generation efficiency. When compared to U.S.
View Article and Find Full Text PDFNovel viologen linked pyrene conjugates permeate cells efficiently and exhibit spacer length dependent DNA damage and cytotoxicity upon photoexcitation.
View Article and Find Full Text PDF[reaction: see text] A novel donor-acceptor conjugate 1 was synthesized, and its interactions with various amino acids have been investigated as compared to the model system 2. The conjugate 1 unusually forms an intramolecular charge-transfer complex in the aqueous medium and undergoes selective binding interactions with tryptophan. The uniqueness of this system is that it selectively recognizes tryptophan among all other amino acids and involves synergistic effects of pi-stacking, electrostatic, and donor-acceptor interactions.
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