Reactive molecular dynamics simulation of the high-temperature pyrolysis of 2,2′,2′′,4,4′,4′′,6,6′,6′′-nonanitro-1,1′:3′,1′′-terphenyl (NONA)

2,2′,2′′,4,4′,4′′,6,6′,6′′-Nonanitro-1,1′:3′,1′′-terphenyl (NONA) is currently recognized as an excellent heat-resistant explosive. To improve the atomistic understanding of the thermal decomposition paths of NONA, we performed a series of reactive force field (ReaxFF) molecular dynamics simulations under extreme conditions of temperature and pressure. The results show that two distinct initial decomposition mechanisms are the homolytic cleavage of the C–NO₂ bond and nitro–nitrite (NO₂ → ONO) isomerization followed by NO fission. Bimolecular and fused ring compounds are found in the subsequent decomposition of NONA. The product identification analysis under finite time steps showed that the gaseous products are CO₂, N₂, and H₂O. The amount of CO₂ is energetically more favorable for the system at high temperature or low density. The carbon-containing clusters are a favorable growth pathway at low temperatures, and this process was further demonstrated by the analysis of diffusion coefficients. The increase of the crystal density accelerates the decomposition of NONA judged by the analysis of reaction kinetic parameters and activation barriers. In the endothermic and exothermic stages, a 20% increase in NONA density increases the activation energies by 3.24 and 0.48 kcal mol⁻¹, respectively. The values of activation energies (49.34–49.82 kcal mol⁻¹) agree with the experimental data in the initial decomposition stage.

The bimolecular and fused ring compounds are found in the high-temperature pyrolysis of NONA using ReaxFF molecular dynamics simulations.     

The modulation effect of pi–pi interactions on the electronic and photochromic properties of viologen complexes containing N,N′-bis(carboxyethyl)-4,4′-bipyridinium

Two viologen complexes containing N,N′-bis(carboxyethyl)-4,4′-bipyridinium (BCEbpy) were prepared, namely [Zn(H₂O)₆]·(BCEbpy)·(p-BDC)·3H₂O (1) and [Co(H₂O)₆]·(BCEbpy)·(p-BDC)·3H₂O (2) (p-H₂BDC = 1,4-benzenedicarboxylic acid), and their crystal structures, photochromism, frontier molecular orbitals, Hirshfeld surfaces and 2D fingerprint plots were investigated. The modulation effects of pi–pi interactions were explored on the electronic and photochromic properties of compounds 1 and 2. Due to the existence of photo-response viologen radicals, both complexes 1 and 2 display excellent photo-response properties in the sequence 1 < 2. The results indicate that compound 1 exhibits intramolecular electron transfer; compound 2 exhibits both intramolecular and intermolecular electron transfer, which is mainly due to the change of electronic and steric structures caused by pi–pi interactions with a faster photo-response rate than that of compound 1. The donor–acceptor modes, matching principles and inter/intramolecular atom–atom close contacts were illustrated by the density functional theory (DFT)-B3LYP/6-311(d,p) method.

Two viologen complexes containing BCEbpy were prepared and displayed excellent photo-response properties by the modulation effect of pi–pi interactions.     

Interpretation of the mechanism of 3,3′-dichloro-4,4′-diamino diphenylmethane synthesis over HY zeolites

Catalytic activities of zeolites HY, Hβ and HZSM-5 in the heterogeneous synthesis of 3,3′-dichloro-4,4′-diaminodiphenyl methane (MOCA) from o-chloroaniline and formaldehyde were pre-screened in an autoclave, and HY demonstrated better performance than others. Kinetic behaviors of MOCA synthesis over HY(11) were further investigated in a fixed bed continuous flow reactor, and under the conditions of the catalyst bed volume = 20 mL (8.14 g), n(o-chloroaniline) : n(HCHO) = 4 : 1, LHSV = 3.5 h⁻¹, 0.5 MPa and 443 K, HCHO conversion and MOCA selectivity steadily fluctuated at high levels of 90–92% and 75–77% during 16 h, respectively. Catalysts were characterized by BET, NH₃-TPD and XRD, products analyzed by HPLC, and reaction intermediates identified by LC/MS and ¹H NMR. The mechanism of MOCA synthesis has been interpreted in detail, which also suggested that deposition of basic intermediates on active sites and accumulation of polymeric by-products in pore channels of the catalyst could cause significant decay of HY(11) activity and selectivity under severe conditions. Supplementary tests on catalyst regeneration confirmed that the acidity and surface area of spent HY(11) could be well recovered after burning off the deposited by-products.

Catalytic activities of zeolites HY, Hβ and HZSM-5 in the heterogeneous synthesis of 3,3′-dichloro-4,4′-diaminodiphenyl methane (MOCA) from o-chloroaniline and formaldehyde were pre-screened in an autoclave, and HY demonstrated better performance than others.     

[2,2′-Bithiophene]-4,4′-dicarboxamide: a novel building block for semiconducting polymers

A novel electron deficient building block [2,2′-bithiophene]-4,4′-dicarboxamide (BTDCA) was designed to lower the highest occupied molecular orbital (HOMO) energy level of polythiophenes in order to achieve a higher open circuit voltage (V_oc) and thus a higher power conversion efficiency in polymer solar cells (PSCs). BTDCA dibromo monomers were conveniently synthesized in four steps, and were used to prepare three thiophene-based D-A polymers, P(BTDCA66-BT) (66BT), P(BTDCA44-BT) (44BT) and P(BTDCA44-TT) (44TT). All the polymers exhibited unipolar hole transport properties, exhibiting mobilities in the range of ∼10⁻⁴ to 10⁻² cm² V⁻¹ s⁻¹ with the highest hole mobility of up to 1.43 × 10⁻² cm² V⁻¹ s⁻¹ achieved for 44BT in bottom-gate bottom-contact organic thin film transistors (OTFTs). In PSCs, these polymers achieved high V_oc''s of 0.81–0.87 V when PCBM or ITIC was used as acceptor. When 44TT was used as donor and ITIC was used as acceptor, a power conversion efficiency (PCE) of up to 4.5% was obtained, a significant improvement when compared with the poly(3-hexylthiophene) (P3HT):ITIC devices, which showed the highest PCE of merely 0.92%.

A new electron acceptor building block, [2,2′-bithiophene]-4,4′-dicarboxamide, is synthesized and used to develop donor polymers for organic solar cells.     

A compatibility study on the glycosylation of 4,4′-dihydroxyazobenzene

Photoresponsive glycoconjugates based on the azobenzene photoswitch are valuable molecules which can be used as tools for the investigation of carbohydrate–protein interactions or as precursors of shape-switchable molecular architectures, for example. To access such compounds, glycosylation of 4,4′-dihydroxyazobenzene (DHAB) is a critical step, frequently giving heterogeneous results because DHAB is a challenging glycosyl acceptor. Therefore, DHAB glucosylation was studied using nine different glycosyl donors, and reaction conditions were systematically varied in order to find a reliable procedure, especially towards the preparation of azobenzene bis-glucosides. Particular emphasis was put on glucosyl donors which were differentiated at the primary 6-position (N₃, OAc) for further functionalisation. The present study allowed us to identify suitable glycosyl donors and reaction conditions matching with DHAB, affording the bis-glycosylated products in fair yields and good stereocontrol.

The glycosylation of 4,4′-dihydroxyazobenzene was investigated to identify suitable conditions providing access to valuable photoswitchable glycoconjugates.     

Mimicking 2,2′:6′,2′′:6′′,2′′′-quaterpyridine complexes for the light-driven hydrogen evolution reaction: synthesis,structural, thermal and physicochemical characterizations

The synthetic difficulties associated with quaterpyridine (qtpy) complexes have limited their use in the formation of various metallosupramolecular architectures in spite of their diverse structural and physicochemical properties. Providing a new facile synthetic route to the synthesis of functionalised qtpy mimics, we herein report the synthesis of three novel –NH₂ functionalized qtpy-like complexes 12–14 with the general formula M(C₁₆H₁₄N₁₂)(NO₃)₂ (M = Co(ii), Ni(ii) and Cu(ii)) in high yield and purity. Characterization of these complexes has been done by single crystal X-ray diffraction (SCXRD), thermogravimetric analysis, UV-Vis, infrared, mass spectrometry and cyclic voltammetry. As indicated by SCXRD, in all the synthesized complexes, the metal ions show a strongly distorted octahedral coordination geometry and typical hydrogen bonding networks involving DAT groups. In addition, complexes 12–14 have been analyzed as potential photocatalysts for hydrogen evolution reaction (HER) displaying good turnover numbers (TONs). Hydrogen produced from these photocatalysts can serve as the possible alternative for fossil fuels. To the best of our knowledge, this is the only study showcasing –NH₂ functionalized qtpy-like complexes of Co(ii), Ni(ii) and Cu(ii) and employing them as photocatalysts for HER. Thus, a single proposed strategy solves two purposes-one related to synthesis while second is related to our environment.

Facile synthesis of three novel –NH₂ functionalized qtpy-like complexes, their characterizations and study of their photocatalytic properties for hydrogen evolution reaction.     

Organic binary charge-transfer compounds of 2,2′ : 6′,2′′ : 6′′,6-trioxotriphenylamine and a pyrene-annulated azaacene as donors

Three binary charge-transfer (CT) compounds resulting from the donor 2,2′ : 6′,2′′ : 6′′,6-trioxotriphenylamine (TOTA) and the acceptors F₄TCNQ and F₄BQ and of a pyrene-annulated azaacene (PAA) with the acceptor F₄TCNQ are reported. The identity of these CT compounds are confirmed by single-crystal X-ray diffraction as well as by IR, UV-vis-NIR and EPR spectroscopy. X-ray diffraction analysis reveals a 1 : 1 stoichiometry for TOTA·F₄TCNQ, a 2 : 1 donor : acceptor ratio in (TOTA)₂·F₄BQ, and a rare 4 : 1 stoichiometry in (PAA)₄·F₄TCNQ, respectively. Metrical parameters of the donor (D) and acceptor (A) constituents as well as IR spectra indicate full CT in TOTA·F₄TCNQ, partial CT in (TOTA)₂·F₄BQ and only a very modest one in (PAA)₄·F₄TCNQ. Intricate packing motifs are present in the crystal lattice with encaged, π-stacked (F₄TCNQ⁻)₂ dimers in TOTA·F₄TCNQ or mixed D/A stacks in the other two compounds. Their solid-state UV-vis-NIR spectra feature CT transitions. The CT compounds with F₄TCNQ are electrical insulators, while (TOTA)₂·F₄BQ is weakly conducting.

Three binary charge-transfer (CT) compounds resulting from the donor 2,2′ : 6′,2′′ : 6′′,6-trioxotriphenylamine (TOTA) and the acceptors F₄TCNQ and F₄BQ and of a pyrene-annulated azaacene (PAA) with the acceptor F₄TCNQ are reported.     

Poly[2,2′-(4,4′-bipyridine)-5,5′-bibenzimidazole] functionalization of carbon black for improving the oxidation stability and oxygen reduction reaction of fuel cells

The rapid oxidation of carbon black (CB) is a major drawback for its use as a catalyst support in polymer electrolyte fuel cells. Here, we synthesize poly[2,2′-(4,4′-bipyridine)-5,5′-bibenzimidazole] (BiPyPBI) as a conducting polymer and use it to functionalize the surface of CB and homogenously anchor platinum metal nanoparticles (Pt-NPs) on a CB surface. The as-prepared materials were confirmed by different spectroscopic techniques, including nuclear magnetic resonance spectroscopy, energy-dispersive X-ray, thermal gravimetric analysis, and scanning-transmittance microscopy. The as-fabricated polymer-based CB catalyst showed an electrochemical surface area (ECSA) of 63.1 cm² mg_Pt⁻¹, giving a catalyst utilization efficiency of 74.3%. Notably, the BiPyPBI-based CB catalyst exhibited remarkable catalytic activity towards oxygen reduction reactions. The onset potential and the diffusion-limiting current density reached 0.66 V and 5.35 mA cm⁻², respectively. Furthermore, oxidation stability testing showed a loss of only 16% of Pt-ECSA for BiPyPBI-based CB compared to a 36% loss of Pt-ECSA for commercial Pt/CB after 5000 potential cycles. These improvements were related to the synergetic effect between the nitrogen-rich BiPyPBI polymer, which promoted the catalytic activity through the structural nitrogen atoms, and demolished the degradation of CB via the wrapping process.

The rapid oxidation of carbon black (CB) is a major drawback for its use as a catalyst support in polymer electrolyte fuel cells.     

Synthesis,cytotoxicity evaluation and molecular docking studies on 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone derivatives

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC, 1) was isolated from seeds of Syzygium nervosum A.Cunn. ex DC. exhibiting intriguing biological activities. Herein, thirty three DMC derivatives including 4′-O-monosubstituted-DMC (2), 7-O-acylated-4-hydroxycoumarin derivatives (3), stilbene–coumarin derivatives (4), 2′,4′-disubstituted-DMC (5), and flavanone derivatives (6), were synthesised through acylation, alkylations, and sulfonylation. These semi-synthetic DMC derivatives were evaluated for in vitro cytotoxicity against six carcinoma cell lines. It was found that most derivatives exhibited higher cytotoxicity than DMC. In particular, 4′-O-caproylated-DMC (2b) and 4′-O-methylated-DMC (2g) displayed the strongest cytotoxicity against SH-SY5Y with IC₅₀ values of 5.20 and 7.52 μM, respectively. Additionally, 4′-O-benzylated-DMC (2h) demonstrated the strongest cytotoxicity against A-549 and FaDu with IC₅₀ values of 9.99 and 13.98 μM, respectively. Our structure–activity relationship (SAR) highlights the importance of 2′-OH and the derivatisation pattern of 4′-OH. Furthermore, molecular docking simulation studies shed further light on how these bioactive compounds interact with cyclin-dependent kinase 2 (CDK2).

Semi-synthetic DMC derivatives were synthesised and displayed biological potency against various cancer cell lines.      

Synthesis and molecular modeling studies of cholinesterase inhibitor dispiro[indoline-3,2′-pyrrolidine-3′,3′′-pyrrolidines]

A set of dispiro[indoline-3,2′-pyrrolidine-3′,3′′-pyrrolidines] 8a–l was regioselectively synthesized utilizing multi-component azomethine cycloaddition reaction of 3-(arylmethylidene)pyrrolidine-2,5-diones 5a–e, isatins 6a–c and sarcosine 7. Single crystal X-ray studies of 8c add conclusive support for the structure. Compounds 8e and 8g reveal cholinesterase inhibitory properties with promising efficacy against both AChE and BChE and were found to be more selective towards AChE than BChE as indicted by the selectivity index like Donepezil (a clinically used cholinesterase inhibitory drug). Molecular modeling studies assist in understanding the bio-observations and identifying the responsible parameters behind biological properties.

Dispiro[indoline-3,2′-pyrrolidine-3′,3′′-pyrrolidines] were regioselectively synthesized revealing cholinesterase (AChE, BChE) inhibitory properties.     

Elucidating the intramolecular contrast in the STM images of 2,4,6-tris(4′,4′′,4′′′-trimethylphenyl)-1,3,5-triazine molecules recorded at room-temperature and at the liquid-solid interface

Star-shaped 2,4,6-tris(4′,4′′,4′′′-trimethylphenyl)-1,3,5-triazine molecules self-assemble at the solid–liquid interface into a compact hexagonal nanoarchitecture on graphite. High resolution scanning tunneling microscopy (STM) images of the molecules reveal intramolecular features. Comparison of the experimental data with calculated molecular charge density contours shows that the molecular features in the STM images correspond to molecular LUMO+2.

Intramolecular contrast in the STM images of 2,4,6-tris(4′,4′′,4′′′-trimethylphenyl)-1,3,5-triazine molecules recorded at room-temperature and at the liquid–solid interface.     

The Effect of 3′,5′-Adenosine Monophosphate on Granulocyte Adhesion

Human granulocyte adhesion to glass capillary tubes was tested in the presence of agents that increase intracellular levels of cyclic 3′,5′-adenosine monophosphate (cAMP). Adhesion was significantly reduced by 10^-3-10^-4 M dibutyryl cAMP, 10^-4-10^-6 M prostaglandin E₁ (PGE₁), 10^-4-10^-6 M histamine, or 10^-3 M theophylline. Adhesion was not suppressed by 10^-4 M theophylline unless it was combined with PGE₁ or histamine. Eosinophil and basophil adhesion was especially sensitive to suppression by the above agents. These findings suggest that intracellular cAMP may play a role in regulation of adhesiveness of human basophils, eosinophils, and neutrophils.     

Novel 1′-homo-N-2′-deoxy-α-nucleosides: synthesis,characterization and biological activity

For the first time, a series of novel 1′-homo-N-2′-deoxy-α-nucleosides containing natural nucleobases as well as 5-fluoro and 5-iodopyrimidine analogs have been synthesized in an efficient manner. Additionally, a high yield protocol for the assembly of a dimeric scaffold containing two sugar moieties linked to the N-1 and N-3 positions of a single pyrimidine base has been accomplished. The structures of the novel homonucleosides were established by a single crystal X-ray structure of 1′-homo-N-2′-deoxy-α-adenosine and NMR studies. The biological activity of these 1′-homo-N-2′-deoxy-α-nucleosides as antiviral (HIV-1 and HBV) and cytotoxic studies was measured in multiple cell systems. The unique structure and easy accessibility of these compounds may allow their use in the design of new nucleoside analogs with potential biological activity and as a scaffold for combinatorial chemistry.

Novel 1′-homo-N-2′-deoxy-α-nucleosides and dimers.     

Photochromic properties of three 2D MOFs based on 1-carboxyethyl-4,4′-bipyridinine

Viologen units have been widely used to impart metal–organic frameworks (MOFs) with photochromic properties. However, construction of a stable photochromic system in viologen MOFs has not been fully explored. Herein, we report three examples of MOFs, namely, {[Cd(CEbpy)(m-BDC)(DMF)]·2H₂O}_n (1), {[Cd(CEbpy)(p-BDC)(H₂O)]·H₂O}_n (2), and {[Zn(CEbpy)(p-HBDC)(p-BDC)_0.5]·H₂O}_n (3) based on benzenedicarboxylic acids (m-H₂BDC = 1,3-benzenedicarboxylic acid, p-H₂BDC = 1,4-benzenedicarboxylic acid) and a viologen-derived ligand 1-carboxyethyl-4,4′-bipyridine (L = CEbpy). As expected, the incorporation of the viologen unit into the frameworks results in the predefined photochromism upon both sunlight and UV-light. Compounds 1–3 feature a two-dimensional (2D) layered structure and are all photochromic due to the formation of CEbpy radicals by photoinduced electron transfer (PET). The aggregates build an interesting stable crystalline framework that exhibits long-lived color constancy in the solid state.

Viologen units have been widely used to impart metal–organic frameworks (MOFs) with photochromic properties.     

Transformation of the coordination nanostructures of 4,4′,4′′-(1,3,5-triazine-2,4,6-triyl) tribenzoic acid molecules on HOPG triggered by the change in the concentration of metal ions

The modulation effects of Cu²⁺/Fe³⁺ ions on the hydrogen-bonded structure of 4,4′,4′′-(1,3,5-triazine-2,4,6-triyl) tribenzoic acid (TATB) on a HOPG surface have been investigated at the liquid–solid interface by scanning tunneling microscopy (STM). STM observations directly demonstrated that the self-assembled honeycomb network of TATB has been dramatically transformed after introducing CuCl₂/FeCl₃ with different concentrations. The metal–organic coordination structures are formed due to the incorporation of the Cu²⁺/Fe³⁺ ions. Interestingly, a Cu²⁺ ion remains coordinated to two COOH groups and only the number of COOH groups involved in coordination doubles when the concentration of Cu²⁺ ions doubled. A Fe³⁺ ion changes from coordination to three COOH groups to two COOH groups after increasing the concentration of Fe³⁺ ions in a mixed solution. Such results suggest that the self-assembled structures of TATB molecules formed by metal–ligand coordination bonds can be effectively adjusted by regulating the concentration of metal ions in a mixed solution, which has rarely been reported before. It explains that the regulatory effect of concentration leads to the diversity of molecular architectures dominated by coordination bonds.

A Cu²⁺ ion maintains coordination with two COOH groups, while a Fe³⁺ ion changes from coordination with three to two COOH groups after increasing the concentration of Cu²⁺/Fe³⁺ ions.     

Effects of glucagon on adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in human plasma and urine

Glucagon, infused intravenously into fasting, well-hydrated, normal men in doses of 25-200 ng/kg per min, induced up to 30-fold increases in both plasma and urinary cyclic AMP. Cyclic GMP levels were unaffected by glucagon. Simultaneous cyclic AMP and inulin clearance studies demonstrated that the glucagon-induced increase in urinary cyclic AMP was entirely due to glomerular filtration of the elevated plasma levels of the nucleotide.The cyclic AMP response to glucagon was not mediated by parathyroid hormone or epinephrine, and trypsintreated glucagon was completely inactive.The perfused rat liver released cyclic AMP into the perfusate in response to glucagon, indicating that the liver is a possible source of the cyclic AMP entering the extracellular fluids in response to glucagon in vivo.     

Base-promoted lipase-catalyzed kinetic resolution of atropisomeric 1,1′-biaryl-2,2′-diols

Herein we report a dramatic acceleration of the lipase-catalyzed kinetic resolution of atropisomeric 1,1′-biaryl-2,2′-diols by the addition of sodium carbonate. This result likely originates from the increased nucleophilicity of the phenolic hydroxyl group toward the acyl-enzyme intermediate. Under these conditions, various substituted C₂-symmetric and non-C₂-symmetric binaphthols and biphenols were efficiently resolved with ∼50% conversion in only 13–30 h with excellent enantioselectivity.

The addition of a stoichiometric amount of Na₂CO₃ dramatically accelerates the lipase-catalyzed kinetic resolution of a range of atropisomeric 1,1′-biaryl-2,2′-diols.     

Kinetic parameters and renal clearances of plasma adenosine 3′,5′-monophosphate and guanosine 3′,5′-monophosphate in man

Kinetic parameters and the renal clearances of plasma adenosine 3',5'-monophosphate (cyclic AMP) and guanosine 3',5'-monophosphate (cyclic GMP) were evaluated in normal subjects using tritium-labeled cyclic nucleotides. Each tracer was administered both by single, rapid intravenous injection and by constant intravenous infusion, and the specific activities of the cyclic nucleotides in plasma and urine were determined.Both cyclic AMP and cyclic GMP were cleared from plasma by glomerular filtration. The kidney was found to add a variable quantity of endogenous cyclic AMP to the tubular urine, amounting to an average of approximately one-third of the total level of cyclic AMP excreted. Plasma was the source of virtually all of the cyclic GMP excreted.Plasma levels of the cyclic nucleotides appeared to be in dynamic steady state. The apparent volumes of distribution of both nucleotides exceeded extracellular fluid volume, averaging 27 and 38% of body weight for cyclic AMP and cyclic GMP, respectively. Plasma production rates ranged from 9 to 17 nmoles/min for cyclic AMP and from 7 to 13 nmoles/min for cyclic GMP. Plasma clearance rates averaged 668 ml/min for cyclic AMP and 855 ml/min for cyclic GMP. Approximately 85% of the elimination of the cyclic nucleotides from the circulation was due to extrarenal clearance.     

Synthesis and evaluation of 3′-[18F]fluorothymidine-5′-squaryl as a bioisostere of 3′-[18F]fluorothymidine-5′-monophosphate

The squaryl moiety has emerged as an important phosphate bioisostere with reportedly greater cell permeability. It has been used in the synthesis of several therapeutic drug molecules including nucleoside and nucleotide analogues but is yet to be evaluated in the context of positron emission tomography (PET) imaging. We have designed, synthesised and evaluated 3′-[¹⁸F]fluorothymidine-5′-squaryl ([¹⁸F]SqFLT) as a bioisostere to 3′-[¹⁸F]fluorothymidine-5′-monophosphate ([¹⁸F]FLTMP) for imaging thymidylate kinase (TMPK) activity. The overall radiochemical yield (RCY) was 6.7 ± 2.5% and radiochemical purity (RCP) was >90%. Biological evaluation in vitro showed low tracer uptake (<0.3% ID mg⁻¹) but significantly discriminated between wildtype HCT116 and CRISPR/Cas9 generated TMPK knockdown HCT116^shTMPK−. Evaluation of [¹⁸F]SqFLT in HCT116 and HCT116^shTMPK− xenograft mouse models showed statistically significant differences in tumour uptake, but lacked an effective tissue retention mechanism, making the radiotracer in its current form unsuitable for PET imaging of proliferation.

[¹⁸F]SqFLT was developed to bypass thymidine kinase 1 (TK1) and evaluated for PET imaging of DNA synthesis.