Publications by authors named "P K Heinonen"

190 Publications

An experimental and computational study of the reaction between pent-3-en-2-yl radicals and oxygen molecules: switching from pure stabilisation to pure decomposition with increasing temperature.

Faraday Discuss 2022 Jul 6. Epub 2022 Jul 6.

Department of Chemistry, University of Helsinki, P. O. Box 55 (A.I. Virtasen Aukio 1), 00014 Helsinki, Finland.

We have used laser-photolysis-photoionization mass spectrometry, quantum chemical calculations, and master equation simulations to investigate the kinetics of the reaction between (/)-pent-3-en-2-yl a resonance-stabilised hydrocarbon radical, and molecular oxygen. The time-resolved experiments were performed over a wide temperature range (240-750 K) at relatively low pressures (0.4-7 Torr) under pseudo-first-order conditions (excess [O]). Helium bath gas was used in most experiments, but nitrogen was employed in a few measurements to investigate the effect of a heavier collider on the kinetics of the studied reaction. The experimental traces were directly used to optimise parameters in the master equation model using the recently implemented trace fitting feature in the MESMER program. At low temperatures ( < 300 K), the reaction proceeds by barrierless recombination reactions to form peroxyl adducts, and the radical traces are single-exponential. Between 326 K and 376 K, equilibration between the reactants and the peroxyl adducts is observed, and the radical traces are multi-exponential. Interestingly, at temperatures above 500 K, single-exponential decays were again observed, although the reaction is much slower than at low temperatures. The master equation simulations revealed that at both low and high temperatures, the radical decay rate is governed by a single eigenvalue. At low temperatures, this eigenvalue corresponds to recombination reactions, and at high temperatures to the phenomenological formation of bimolecular products. Between low and high temperatures (the exact temperature thresholds depend on [O]), there is a region of avoided crossing in which the rate coefficient "jumps" from one eigencurve to the other. Although chemically significant eigenvalues are not well separated from internal energy relaxation eigenvalues at elevated temperatures (600 K at 0.01 bar, 850 K at 100 bar), we observed that many of the Bartis-Widom rate coefficients produced by the master equation model were valid up to 1500 K. Our simulations predict that the most important reaction channel at high temperatures is the formation of (/)-penta-1,3-diene and hydroperoxyl. The experimentally constrained master equation model was used to simulate the title reaction over a wide range of conditions. To facilitate the use of our results in autoignition and combustion models, modified Arrhenius representations are given for the most important reaction channels.
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http://dx.doi.org/10.1039/d2fd00031hDOI Listing
July 2022

Solving the discrepancy between the direct and relative-rate determinations of unimolecular reaction kinetics of dimethyl-substituted Criegee intermediate (CH)COO using a new photolytic precursor.

Phys Chem Chem Phys 2022 Feb 23;24(8):5211-5219. Epub 2022 Feb 23.

Department of Chemistry, University of Helsinki, P.O. Box 55 (A.I. Virtasen aukio 1), Helsinki, FI-00014, Finland.

We have performed direct kinetic measurements of the thermal unimolecular reaction of (CH)COO in the temperature range 243-340 K and pressure range 5-350 Torr using time-resolved UV-absorption spectroscopy. We have utilized a new photolytic precursor, 2-bromo-2-iodopropane ((CH)CIBr), which photolysis at 213 nm in the presence of O produces acetone oxide, (CH)COO. The results show that the thermal unimolecular reaction is even more important main loss process of (CH)COO in the atmosphere than direct kinetic studies have suggested hitherto. The current experiments show that the unimolecular reaction rate of (CH)COO at 296 K and atmospheric pressure is 899 ± 42 s. Probably more importantly, current measurements bring the direct and relative-rate measurements of thermal unimolecular reaction kinetics of (CH)COO into quantitative agreement.
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http://dx.doi.org/10.1039/d1cp02270aDOI Listing
February 2022

Missing Selectivity of Targeted 4β-Phorbol Prodrugs Expected to be Potential Chemotherapeutics.

ACS Med Chem Lett 2020 May 23;11(5):671-677. Epub 2019 Dec 23.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 162, DK-2100 Copenhagen, Denmark.

Targeting cytotoxic 4β-phorbol esters toward cancer tissue was attempted by conjugating a 4β-pborbol derivative with substrates for the proteases prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) expressed in cancer tissue. The hydrophilic peptide moiety was hypothesized to prevent penetration of the prodrugs into cells and prevent interaction with PKC. Cleavage of the peptide in cancer tumors was envisioned to release lipophilic cytotoxins, which subsequently penetrate into cancer cells. The 4β-phorbol esters were prepared from 4β-phorbol isolated from seeds, while the peptides were prepared by solid-phase synthesis. Cellular assays revealed activation of PKC by the prodrugs and efficient killing of both peptidase positive as well as peptidase negative cells. Consequently no selectivity for enzyme expressing cells was found.
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http://dx.doi.org/10.1021/acsmedchemlett.9b00554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236034PMC
May 2020

Tuning the stability of alkoxyisopropyl protection groups.

Beilstein J Org Chem 2019 21;15:746-751. Epub 2019 Mar 21.

Department of Chemistry, University of Helsinki, P.O.Box 55 (A.I.Virtasen aukio 1), FIN-00014 Helsinki, Finland.

Five different 2-alkoxypropan-2-yl groups are introduced as acid-labile protecting groups for the 5'- and 3'-hydroxy groups of a 2'-deoxynucleoside. All studied protecting groups were readily introduced with good to excellent yields using the appropriate enol ether as a reagent and 0.5 to 1 mol % toluenesulfonic acid as a catalyst. The protected compounds could be purified by silica gel column chromatography without degradation. The compatibility of these protecting groups in parallel use with benzoyl and silyl groups was verified. The stabilities of the different alkoxy acetal protecting groups were compared by following the kinetics of their hydrolysis at 25.0 °C in buffered solutions through an HPLC method. In the pH range 4.94 to 6.82 the hydrolysis reactions are of first order in the hydronium ion. The rate of hydrolysis correlates with the electron-donating or electron-withdrawing ability of the corresponding alkoxy group. The studied 2-alkoxypropan-2-yl groups and the relative rate constants for their cleavage from the 5'-hydroxy group of 2'-deoxythymidine were: cyclohexyloxy ( = 7.7), isopropoxy (7.4), methoxy (1), benzyloxy (0.6) and 2,2,2-trifluoroethyloxy (0.04). The attachment of the same groups to the 3'-hydroxy group are from 1.3 to 1.9-fold more stable. The most reactive of these acetone-based acetal groups are faster removed than a dimethoxytrityl group, and they are easier to cleave completely in solution. The structural variation allows steering of the stability and lipophilicity of the compounds in some range.
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http://dx.doi.org/10.3762/bjoc.15.70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444389PMC
March 2019

Distribution of female genital tract anomalies in two classifications.

Eur J Obstet Gynecol Reprod Biol 2016 Nov 20;206:141-146. Epub 2016 Sep 20.

School of Medicine, University of Tampere, Tampere, Finland; Department of Obstetrics and Gynecology, University Hospital of Tampere, Tampere, Finland. Electronic address:

Objective: This study assessed the distribution of Müllerian duct anomalies in two verified classifications of female genital tract malformations, and the presence of associated renal defects.

Study Design: 621 women with confirmed female genital tract anomalies were retrospectively grouped under the European (ESHRE/ESGE) and the American (AFS) classification. The diagnosis of uterine malformation was based on findings in hysterosalpingography, two-dimensional ultrasonography, endoscopies, laparotomy, cesarean section and magnetic resonance imaging in 97.3% of cases. Renal status was determined in 378 patients, including 5 with normal uterus and vagina.

Results: The European classification covered all 621 women studied. Uterine anomalies without cervical or vaginal anomaly were found in 302 (48.6%) patients. Uterine anomaly was associated with vaginal anomaly in 45.2%, and vaginal anomaly alone was found in 26 (4.2%) cases. Septate uterus was the most common (49.1%) of all genital tract anomalies, followed by bicorporeal uteri (18.2%). The American classification covered 590 (95%) out of the 621 women with genital tract anomalies. The American system did not take into account vaginal anomalies in 170 (34.7%) and cervical anomalies in 174 (35.5%) out of 490 cases with uterine malformations. Renal abnormalities were found in 71 (18.8%) out of 378 women, unilateral renal agenesis being the most common defect (12.2%), also found in 4 women without Müllerian duct anomaly.

Conclusions: The European classification sufficiently covered uterine and vaginal abnormalities. The distribution of the main uterine anomalies was equal in both classifications. The American system missed cervical and vaginal anomalies associated with uterine anomalies. Evaluation of renal system is recommended for all patients with genital tract anomalies.
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http://dx.doi.org/10.1016/j.ejogrb.2016.09.009DOI Listing
November 2016
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