skip to main content

Title: Kinetic Control in the Regioselective Alkylation of Pterin Sensitizers: A Synthetic, Photochemical, and Theoretical Study
Abstract

Alkylation patterns and excited‐state properties of pterins were examined both experimentally and theoretically. 2DNMRspectroscopy was used to characterize the pterin derivatives, revealing undoubtedly that the decyl chains were coupled to either the O4 or N3 sites on the pterin. At a temperature of 70°C, the pterin alkylation regioselectively favored the O4 over the N3. The O4 was also favored when using solvents, in which the reactants had increased solubility, namelyN,N‐dimethylformamide andN,N‐dimethylacetamide, rather than solvents in which the reactants had very low solubility (tetrahydrofuran and dichloromethane). Density functional theory (DFT) computed enthalpies correlate to regioselectivity being kinetically driven because the less stable O‐isomer forms in higher yield than the more stable N‐isomer. Once formed these compounds did not interconvert thermally or undergo a unimolecular “walk” rearrangement. Mechanistic rationale for the factors underlying the regioselective alkylation of pterins is suggested, where kinetic rather than thermodynamic factors are key in the higher yield of theO‐isomer. Computations also predicted greater solubility and reduced triplet state energetics thereby improving the properties of the alkylated pterins as1O2sensitizers. Insight on thermal and photostability of the alkylated pterins is also provided.

Authors:
 ;  ;  ;  ;  ;  ;  
Publication Date:
NSF-PAR ID:
10075028
Journal Name:
Photochemistry and Photobiology
Volume:
94
Issue:
5
Page Range or eLocation-ID:
p. 834-844
ISSN:
0031-8655
Publisher:
Wiley-Blackwell
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    Intralipid is a lipid emulsion used in photodynamic therapy (PDT) for its light scattering and tissue‐simulating properties. The purpose of this study is to determine whether or not Intralipid undergoes photooxidation, and we have carried out an Intralipid peroxide trapping study using a series of phosphines [2′‐dicyclohexylphosphino‐2,6‐dimethoxy‐1,1′‐biphenyl‐3‐sulfonate, 3‐(diphenylphosphino)benzenesulfonate, triphenylphosphine‐3,3′,3′′‐trisulfonate and triphenylphosphine]. Our new findings are as follows: (1) An oxygen atom is transferred from Intralipid peroxide to the phosphine traps in the dark, after the photooxidation of Intralipid. 3‐(Diphenylphosphino)benzenesulfonate is the most suitable trap in the series owing to a balance of nucleophilicity and water solubility. (2) Phosphine trapping and monitoring by31PNMRare effective in quantifying the peroxides in H2O. An advantage of the technique is that peroxides are detected in H2O; deuteratedNMRsolvents are not required. (3) The percent yield of the peroxides increased linearly with the increase in fluence from 45 to 180 J cm−2based on our trapping experiments. (4) The photooxidation yields quantitated by the phosphines and31PNMRare supported by the direct1HNMRdetection using deuteratedNMRsolvents. These data provide the first steps in the development of Intralipid peroxide quantitation afterPDTusing phosphine trapping and31PNMRspectroscopy.

  2. Rationale

    It is imperative to understand how chemical preservation alters tissue isotopic compositions before using historical samples in ecological studies. Specifically, although compound‐specific isotope analysis of amino acids (CSIA‐AA) is becoming a widely used tool, there is little information on how preservation techniques affect amino acidδ15N values.

    Methods

    We evaluated the effects of chemical preservatives on bulk tissueδ13C andδ15N and amino acidδ15N values, measured by gas chromatography/isotope ratio mass spectrometry (GC/IRMS), of (a) tuna (Thunnus albacares) and squid (Dosidicus gigas) muscle tissues that were fixed in formaldehyde and stored in ethanol for 2 years and (b) two copepod species,Calanus pacificusandEucalanus californicus, which were preserved in formaldehyde for 24–25 years.

    Results

    Tissues in formaldehyde‐ethanol had higher bulkδ15N values (+1.4,D. gigas; +1.6‰,T. albacares), higherδ13C values forD. gigas(+0.5‰), and lowerδ13C values forT. albacares(−0.8‰) than frozen samples. The bulkδ15N values from copepods were not different those from frozen samples, although theδ13C values from both species were lower (−1.0‰ forE. californicusand −2.2‰ forC. pacificus) than those from frozen samples. The mean amino acidδ15N values from chemically preserved tissues were largely within 1‰ of those of frozen tissues, but the phenylalanineδ15N values were altered to a larger extent (range: 0.5–4.5‰).

    Conclusions

    The effectsmore »of preservation on bulkδ13C values were variable, where the direction and magnitude of change varied among taxa. The changes in bulkδ15N values associated with chemical preservation were mostly minimal, suggesting that storage in formaldehyde or ethanol will not affect the interpretation ofδ15N values used in ecological studies. The preservation effects on amino acidδ15N values were also mostly minimal, mirroring bulkδ15N trends, which is promising for future CSIA‐AA studies of archived specimens. However, there were substantial differences in phenylalanine and valineδ15N values, which we speculate resulted from interference in the chromatographic resolution of unknown compounds rather than alteration of tissue isotopic composition due to chemical preservation.

    « less
  3. 1. Ants are widely regarded as ‘ecosystem engineers’ because their nest construction and contributions to nutrient cycling change the biological, chemical, and physical properties of the soil around their nests. Despite increasing attention to ant manipulation of soil ecosystems, the extent to which many common species influence soil properties, as well as nutrient uptake and community composition of plants near nests, is still unknown.

    2. This study tested hypotheses that activities of a common subalpine ant,Formica podzolica, alter soil moisture and pH, redistribute nitrogen around nests, and affect plant species abundance and ground cover.

    3. A combination of field sampling techniques showed that distance from a nest had a positive relationship with soil moisture and a negative relationship with plant abundance next to and downhill from nests. Slope aspect also affected plant communities, with downhill transects having higher plant cover and above‐ground biomass than uphill transects. A stable isotope analysis did not reveal that plants near nests had enriched15N, but there were substantial differences in15N among sites.

    4. Overall, this study uncovers significant impacts ofF. podzolicaon the subalpine microhabitats directly surrounding their nests.

  4. The freshwater red algal order Thoreales has triphasic life history composed of a diminutive diploid “Chantransia” stage, a distinctive macroscopic gametophyte with multi‐axial growth and carposporophytes that develop on the gametophyte thallus. This order is comprised of two genera,ThoreaandNemalionopsis.Thoreahas been widely reported with numerous species, whereasNemalionopsishas been more rarely observed with only a few species described.DNAsequences from three loci (rbcL,cox1, andLSU) were used to examine the phylogenetic affinity of specimens collected from geographically distant locations including North America, South America, Europe, Pacific Islands, Southeast Asia, China, and India. Sixteen species ofThoreaand two species ofNemalionopsiswere recognized. Morphological observations confirmed the distinctness of the two genera and also provided some characters to distinguish species. However, many of the collections were in “Chantransia” stage rather than gametophyte stage, meaning that key diagnostic morphological characters were unavailable. Three new species are proposed primarily based on theDNAsequence data generated in this study,Thorea kokosinga‐pueschelii,T. mauitukitukii,andT. quisqueyana. In addition to these newly described species, oneDNAsequence from GenBank was not closely associated with otherThoreaclades and may represent further diversity in the genus. Two species inNemalionopsisare recognized,N. shawiiandN. parkerinom. et stat. nov.Thoreaharbors more diversity than had been recognized by morphological data alone. Distribution data indicated thatNemalionopsisis common in the Pacificmore »region, whereasThoreais more globally distributed. Most species ofThoreahave a regional distribution, butThorea hispidaappears to be cosmopolitan.

    « less
  5. Premise

    Male gametophytes of most seed plants deliver sperm to eggs via a pollen tube. Pollen tube growth rates (PTGRs) of angiosperms are exceptionally rapid, a pattern attributed to more effective haploid selection under stronger pollen competition. Paradoxically, whole genome duplication (WGD) has been common in angiosperms but rare in gymnosperms. Pollen tube polyploidy should initially acceleratePTGRbecause increased heterozygosity and gene dosage should increase metabolic rates. However, polyploidy should also independently increase tube cell size, causing more work which should decelerate growth. We asked how genome size changes have affected the evolution of seed plantPTGRs.

    Methods

    We assembled a phylogenetic tree of 451 species with knownPTGRs. We then used comparative phylogenetic methods to detect effects of neo‐polyploidy (within‐genus origins),DNAcontent, andWGDhistory onPTGR, and correlated evolution ofPTGRandDNAcontent.

    Results

    Gymnosperms had significantly higherDNAcontent and slowerPTGRoptima than angiosperms, and theirPTGRandDNAcontent were negatively correlated. For angiosperms, 89% of model weight favored Ornstein‐Uhlenbeck models with a fasterPTGRoptimum for neo‐polyploids, whereasPTGRandDNAcontent were not correlated. For within‐genus and intraspecific‐cytotype pairs,PTGRs of neo‐polyploids < paleo‐polyploids.

    Conclusions

    Genome size increases should negatively affectPTGRwhen genetic consequences ofWGDs are minimized, as found in intra‐specific autopolyploids (low heterosis) and gymnosperms (fewWGDs). But in angiosperms, the higherPTGRoptimum of neo‐polyploidsmore »and non‐negativePTGRDNAcontent correlation suggest that recurrentWGDs have caused substantialPTGRevolution in a non‐haploid state.

    « less