СИНТЕЗ МОДИФІКОВАНИХ ФЛУОРЕСЦЕЇНІВ ДЛЯ ВИКОРИСТАННЯ У КЛІК-РЕАКЦІЯХ
Reactions of azide-alkilic cycloaddition are well known since 1893. At the same time, with the elaboration of click chemistry, the techniques of labelling biological objects, particularly by fluorescent dyes, were widely developed. The use of fluorescent labels provides the ability to visually monit...
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V.I.Vernadsky Institute of General and Inorganic Chemistry
2020
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Ukrainian Chemistry Journal| _version_ | 1871465432805801984 |
|---|---|
| author | Selin, Roman Chernii, Viktor Mokhir, Andriy |
| author_facet | Selin, Roman Chernii, Viktor Mokhir, Andriy |
| author_institution_txt_mv | [
{
"author": "Roman Selin",
"institution": "SC Princeton Biomolecular Research Labs"
},
{
"author": "Viktor Chernii",
"institution": "Vernadsky Institute of general and inorganic chemistry"
},
{
"author": "Andriy Mokhir",
"institution": "Friedrich-Alexander-University of Erlangen-Nürnberg, Dapartment of Chemistry and Pharmacy, Organic Chemistry Chair II, Henkestr. 42, 91054 Erlangen"
}
] |
| author_sort | Selin, Roman |
| baseUrl_str | https://ucj.org.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-22T08:23:42Z |
| description | Reactions of azide-alkilic cycloaddition are well known since 1893. At the same time, with the elaboration of click chemistry, the techniques of labelling biological objects, particularly by fluorescent dyes, were widely developed. The use of fluorescent labels provides the ability to visually monitor the process streamlines hardware load and reduces research time. Fluorescein is among the fluorophores mostly used for labelling of biomolecules due to its high quantum yields and good stability in biological media. However, despite of commercial availability of fluorescein derivatives functionalized for use in click reactions, methods for their synthesis are virtually absent in the literature. Therefore, we have developed a reliable and effective methodic for the synthesis of functionalized fluoresceines for the use in the click reactions. Synthesis of diacetyl N-(4-azidobutyl)-fluoresceine-5(6)-carboxamide was performed in six stages, starting form resorcinol and trimellitic acid anhydride. The diacetylated analogue was synthesized for the click modifications in the “soft” conditions, since N-(4-azidobutyl)-fluorescein-5(6)-carboxamide is poorly soluble in the classic organic solvents. Proposed synthetic protocol allows to increase the yield of the final and intermediate compounds and to optimized the procedure of their isolation and purification. |
| doi_str_mv | 10.33609/0041-6045.86.3.2020.3-8 |
| first_indexed | 2025-09-24T17:43:24Z |
| format | Article |
| fulltext |
НЕОРГАНІЧНА ХІМІЯ
ISSN 0041-6045. УКР . ХІМ . ЖУРН ., 2020, т . 86, № 3 3
UDC 544.6.018. doi: 10.33609/0041-6045.86.3.2020.3-8
R. Selin, V. Chernii, A. Mokhir
SYNTHESIS OF MODYFIED FLUORESCEINE FOR CLICK REACTIONS
1Vernadsky Institute of General and Inorganic Chemistry NAS,32/34 Palladina prosp. Kyiv, 03142
Ukraine.
2SC Princeton Biomolecular Research Labs, Saperne Pole St., 26A, 01042 Kyiv, Ukraine.
3Friedrich-Alexander-University of Erlangen-Nürnberg, Dapartment of Chemistry and Pharmacy,
Organic Chemistry Chair II, Henkestr. 42, 91054 Erlangen, Germany.
*е-mail: selin.roman.oleksandrovich@gmail.com
The methodology of the synthesis of the modified fluoresceins for the click reactions
was developed. Proposed synthetic protocol allows to increase the yield of the final and
intermediate compounds and to optimized the procedure of their isolation and purifica-
tion.
K e y w o r d s: modified fluorescein, fluorescein, click reaction.
INTRODUCTION. Reactions of azide-
alkilic cycloaddition are well known since
1893. However, after discovering cupper-
promoted azid-alkilic cycloaddition [1, 2]
this type of reactions gained new life. Due to
the high yields, mild reaction temperatures,
selectivity of the process and variability of
suitable solvents this type of reaction be-
came integral part of click-chemistry.
At the same time, with the elaboration of
click chemistry, the techniques of labelling
biological objects, particularly by fluores-
cent dyes, were widely developed. The use
of fluorescent labels provides the ability to
visually monitor the process streamlines
hardware load and reduces research time [4].
Also, unlike most radioisotope probes, the
vast majority of fluorescent dyes retain their
properties over time. These factors have
made fluorescence labeling one of the most
widely used analytical methods in biochem-
istry, biology and medicine.
Besides the use for synthesis of the new
biologically active compounds [5], azide-
alkyne cyclic coupling reaction due to its
mild conditions allows the modification of
macromolecules in vivo. For example, cup-
per-free click labeling and chondrocyte
tracking in vivo is reported in [6].
Fluorescein is among the fluorophores
mostly used for labelling of biomolecules
due to its high quantum yields and good sta-
bility in biological media [7]. However,
despite of commercial availability of
© R. Selin, V. Chernii, A. Mokhir
mailto:selin.roman.oleksandrovich@gmail.com
R. Selin, V. Chernii, A. Mokhir
4 ISSN 0041-6045. УКР . ХІМ . ЖУРН ., 2020, т . 86, № 3
fluorescein derivatives functionalized for use
in click reactions, methods for their synthe-
sis are virtually absent in the literature.
Therefore, we have developed a reliable
and effective methodic for the synthesis of
functionalized fluoresceines for the use in
the click reactions.
EXPERIMENT AND DISCUSSION OF
THE RESULTS. Synthesis of diacetyl N-(4-
azidobutyl)-fluoresceine-5(6)-carboxamide
(6) was performed in six stages, starting
form resorcinol and trimellitic acid anhy-
dride. The diacetylated analogue was syn-
thesized for the click modifications in the
“soft” conditions, since N-(4-azidobutyl)-
fluorescein-5(6)-carboxamide (5) is poorly
soluble in the classic organic solvents.
5(6)-carboxyfluorescein (1) was obtained by
the reaction of resorcinol and trimellitic an-
hydride in methane sulfonic acid at 110° C.
During the reaction equimolar mixture of 5th
and 6th isomers is forming. Precipitation
from water and crystallization from the dif-
ferent solvents gave insufficient result in
separation of these two isomers. Cause it
similar spectral properties, it was decided to
work with the equimolar mixture of two
isomers.
Diacetyl 5(6)-carboxyfluoresceine (2)
was obtained by the refluxing of fluores-
cein (1) with acetic anhydride in pyridine
(Fig. 1).
Synthesis of the azides was per-
formed without excess of light and during
purification temperature maintained below
350. All azides were used in the next step
with an excess and without purification.
1,4-diazidobutane (3) was obtained by
the standard reaction of 1,4-dibromobutane
with an excess of sodium azide in dry
Fig. 1: Synthesis of diacetyl 5(6)-
carboxyfluorescein (2)
dimethylformamide. Reaction was con-
trolled by gas chromatography. After reac-
tion was complete, reaction mixture was di-
luted with water and extracted with diethyl
ether. Organic fraction was evaporated under
vacuum without heating and diluted with
tetrahydrofuran. Solution of 1,4-
diazidobutane (3) was used in the next step
without purification.
1-amino-4-azidobutane (4) was obtained
by the reduction of azide group of 1,4-
diazidobutane (3) with triphenylphosphine.
Triphenylphosphine was added portion wise
upon cooling. An excess of 1,4-
diazidobutane (3) was used in order to pre-
vent formation of 1,4-diaminobutane. Reac-
tion was controlled by gas chromatography
(Fig. 2).
Fig. 2: Synthesis of 1-amino-4-azidobutane (4)
Synthesis of modyfied fluoresceine for click reactions
ISSN 0041-6045. УКР . ХІМ . ЖУРН ., 2020, т . 86, № 3 5
N-(4-azidobutyl)-fluoresceine-5(6)-
carboxamide (5) was obtained by the reac-
tion of the daicetyl 5(6)-carboxyfluoresceine
(2) with 1,1′-carbonyldiimidazole (CDI) and
an excess of 1-amino-4-azidobutane (4). The
partial hydrolysis of acetyl group during the
synthesis was noticed. Hydrolysis of acetyl
groups with an excess of ammonia water
solution was performed in order to simplify
the purification.
Diacetyl N-(4-azidobutyl)-fluoresceine-
5(6)-carboxamide (6) was obtained by the
refluxing of fluorescein (5) with acetic an-
hydride in pyridine. (Fig. 3).
Fig. 3: Synthesis of diacetyl N-(4-
azidobutyl)- fluorescein-5(6)-carboxamide (6)
Same synthesis could be performed without
protection with acetyl group. However, it’s
easier to work with acetylated fluorescein
derivative.
We prefer to use acetylated fluorescein
because it is nicely soluble in classic organic
solvents, this simplifies further handling
with labeled compounds. Acetyl group could
be easily hydrolyzed by using of classic
methods.
For the fluorescein (5) UV-Vis and fluo-
rescence spectra were registered. Its absorb-
ance maximum wavelength is located at 494
nm and fluorescence maximum is located at
520 nm (Fig. 4), that is similar to corre-
sponding maxima of non-functionalized
uranin (500 nm and 521 nm correspondingly
[8]).
5(6)-carboxyfluorescein (1): trimellitic
acid anhydride (10 g, 52.0 mmol) was dis-
solved in methane sulfonic acid (50 ml) and
resorcinol (12 g, 109.3 mmol, 2.1 eq) was
added. The reaction mixture was stirred at
110 °C for two hours. At the end of the reac-
tion, the reaction mixture was cooled and
poured into water, the precipitate was fil-
tered, crystallized from water and dried in
air at 100 °C to obtain 5(6)-
carboxyfluorescein (16.4 g, 44 mmol, 84%),
which was used without purification in the
next step.
Diacetyl 5(6)-carboxyfluorescein (2): 5
(6)-carboxyfluorescein (10 g, 26.6 mmol)
was dissolved in 50 ml of dry pyridine and
acetic anhydride (10 ml, 106.21 mmol, 4
equiv.) was added drop wise at room tem-
perature and reaction mixture was stirred at
room temperature overnight. At the end of
the reaction, the mixture was evaporated,
dissolved in ethyl acetate (100 mL) and
washed with 1M HCl (3×50 mL), water (100
mL) and Brine (100 mL) solution, dried over
sodium sulfate and evaporated to dry in vac-
uo to give diacetyl 5(6)-carboxyfluorescein
(12.2 g, 26.6 mmol, 100%). 1H NMR (400
MHz, DMSO-d6) δ: 8.47 (dd, J = 1.5, 0.8
Hz, 1H), 8.33 (dd, J = 8.0, 1.5 Hz, 1H), 8.28
R. Selin, V. Chernii, A. Mokhir
6 ISSN 0041-6045. УКР . ХІМ . ЖУРН ., 2020, т . 86, № 3
Fig. 4: Normalized UV-Vis (a) and fluorescence
spectra (b) of N-(4-azidobutyl)-fluorescein-5
(6)-carboxamide (5)
(dd, J = 8.0, 1.3 Hz, 1H), 8.15 (dd, J = 8.0,
0.8 Hz, 1H), 7.81 (dd, J = 1.3, 0.8 Hz, 1H),
7.48 (dd, J = 8.1, 0.7 Hz, 1H), 7.28 - 7.20
(m, 3H), 6.98-6.86 (m, 7H), 2.29 (s, 12H).
1,4-diazidobutane (3): 1,4-
dibromobutane (20 ml, 167.5 mmol) was
dissolved in dry dimethylformamide (100
ml) and sodium azide (43.54 g, 669.9 mmol,
4 equiv.) was added. The reaction mixture
was stirred overnight at 55 °C (control by
gas chromatography), cooled to room tem-
perature, poured into 300 ml of water and
extracted with diethyl ether. The organic
extract was evaporated without heating on a
vacuum pump to obtain quantitatively 1,4-
diazidobutane. The reaction was carried out
in the cold season with minimal access of
light. Solvent was not evaporated to dry. The
reaction mixture was used in the next step
without purification. Quantitative yield. 1H
NMR (400 MHz, Chloroform-d) δ 3.32 (td, J
= 5.1, 3.9, 2.2 Hz, 4H), 1.73 – 1.62 (m, 4H).
1-amino-4-azidobutane (4): Freshly prepared
1,4-diazidobutane (167.5 mmol) was dis-
solved in tetrahydrofuran (200 ml), the reac-
tion mixture was cooled in an ice bath and
triphenylphosphine (13.2 g, 50.25 mmol, 0.3
eq.) was added in small portions with control
of gas evolution. Upon completion of the
addition, the reaction mixture was gradually
brought to room temperature and stirred
overnight. Product formation was monitored
by gas chromatography. At the end of the
reaction, the reaction mixture was diluted
with 200 ml of 2N HCl and tetrahydrofuran
was evaporated under vacuum The aqueous
fraction was extracted with dichloromethane
(3 × 100 ml) basified with 25% aqueous
NaOH and extracted with diethyl ether (3 ×
100 ml), dried over sodium sulfate and
evaporated without heating on a vacuum
pump. After evaporation, 1-amino-4-
azidobutane is diluted with dry
tetrahydrofuran to obtain a 25% solution
which was used without purification in the
next step. Quantitative yield. 1H NMR (400
MHz, DMSO-d6) δ 3.30 (t, J = 6.9 Hz, 2H),
2.79 (bs, 2H), 2.54 (m, 2H), 1.60 – 1.44 (m,
2H), 1.49 – 1.29 (m, 2H).
N-(4-azidobutyl)-fluorescein-5(6)-
carboxamide (5): Diacetyl 5(6)-
carboxyfluorescein (5 g, 10.86 mmol) was
dissolved in dry tetrahydrofuran (50 ml) and
1,1′-carbonyldiimidazole (CDI) (1.93 g,
11.94) was added portion wise. (1.93 g,
11.94 mmol, 1.1 equiv.). The reaction mix-
ture was stirred at room temperature over-
night and a solution of 1-amino-4-
azidobutane (4.95 g, 43.44 mmol, 4 equiv.)
in tetrahydrofuran (20 ml) was added at once
Synthesis of modyfied fluoresceine for click reactions
ISSN 0041-6045. УКР . ХІМ . ЖУРН ., 2020, т . 86, № 3 7
with vigorous stirring. The reaction mixture
was stirred for 2 hours, evaporated to dry
and diluted with 50 ml 1N HCl. The aqueous
fraction was extracted with dichloromethane
(3 × 25 ml) and the organic fraction was bas-
ified with 25% ammonia solution upon vig-
orous stirring. After a few minutes, the reac-
tion mixture was neutralized with concen-
trated hydrochloric acid, the precipitate was
filtered and dried on a vacuum pump to ob-
tain N-(4-azidobutyl)-fluorescein-5(6)-
carboxamide (4.25 g, 9.01 mmol, 83%). 1H
NMR (400 MHz, DMSO-d6) δ 10.13 (bs,
2H), 8.87 (t, J = 5.7 Hz, 1H), 8.49 – 8.44 (m,
1H), 8.25 (dd, J = 8.0, 1.6 Hz, 1H), 7.38 (dd,
J = 8.0, 0.7 Hz, 1H), 6.72 (d, J = 2.1 Hz,
2H), 6.63 – 6.52 (m, 4H), 3.44 – 3.30 (m,
4H), 1.62 (h, J = 3.6 Hz, 4H).
Diacetyl N-(4-azidobutyl)-fluorescein-
5(6)-carboxamide (6): N-(4-azidobutyl)-
fluorescein-5(6)-carboxamide (4.25 g, 9.01
mmol) was dissolved in 50 ml dry pyridine
and acetic anhydride (3.4 ml, 36.04 mmol, 4
equiv.) was added drop wise and reaction
mixture was stirred at room temperature
overnight. At the end of the reaction, the
mixture was evaporated, dissolved in ethyl
acetate and washed with 1M HCl (20 mL),
water and Brine solution, dried over sodium
sulfate and evaporated to dryness in vacuo to
give diacetyl N-(4-azidobutyl)-fluorescein-
5(6)-carboxamide (4.96 g, 9.01 mmol,
100%).1H NMR (400 MHz, Chloroform-d):
δ 8.33 (dd, J = 1.6, 0.8 Hz, 1H), 8.14 (dd, J
= 8.0, 1.6 Hz, 1H), 7.22 (dd, J = 8.0, 0.7 Hz,
1H), 7.05 (dd, J = 2.1, 0.5 Hz, 2H), 6.79 –
6.68 (m, 4H), 3.48 (q, J = 6.4 Hz, 2H), 3.28
(t, J = 6.3 Hz, 2H), 2.25 (s, 6H), 1.80 – 1.55
(m, 4H).
CONCLUSIONS. Functionalized fluore-
sceines modified for click reactions were
synthesized by the developed reliable proto-
col. Both 5th and 6th fluorescein isomers are
applicable for the click reactions, dependent-
ly from the required reaction conditions. Fi-
nal diacetyl N-(4-azidobutyl)-fluorescein-
5(6)-carboxamide (6) was obtained in 6
steps synthesis with total yield more than
70%. After click reaction acetyl groups of
this dye could be easily hydrolyzed by clas-
sic methods.
ACKNOWLEDGEMENT
The project leading to these results has re-
ceived funding from the European Union's
Horizon 2020 research and innovation pro-
gram under the Marie Sklodowska-Qurie
grant agreement No 778245.
СИНТЕЗ МОДИФІКОВАНИХ ФЛУОРЕ-
СЦЕЇНІВ ДЛЯ ВИКОРИСТАННЯ У КЛІК-
РЕАКЦІЯХ
Селін Р.1,2, Черній В.1, Мохір А.3
1Інститут загальної та неорганічної хімії ім.
В.І.Вернадського НАН України, просп. Ака-
деміка Палладіна, 32-34, Київ, 03142, Украї-
на.
2Прінстонські лабораторії біомолекулярних
досліджень, Україна, вул. Мурманська, 1,
Київ, 02094, Україна.
3Універсітет Фрідріха-Олександра в Ерлан-
гені-Нюрнберзі, факультет хімії і фармаце-
втики, кафедра органічної хімії II, Хенкешт-
рассе 42, 91054 Ерланген, Німеччина.
*е-mail:
selin.roman.oleksandrovich@gmail.com
Розроблено методологію синтезу модифіко-
ваних азидною групою флуоресцеїнів для
використання у клік-реакціях. Були покра-
mailto:selin.roman.oleksandrovich@gmail.com
R. Selin, V. Chernii, A. Mokhir
8 ISSN 0041-6045. УКР . ХІМ . ЖУРН ., 2020, т . 86, № 3
щені виходи описаних стадій синтезу та оп-
тимізовано способи виділення та очищення
кінцевих та проміжних сполук.
К л ю ч о в і с л о в а: флуоресцеїн, азидза-
міщені флуоресцеїни, клік реакції.
СИНТЕЗ МОДИФИЦИРОВАННЫХ ФЛУО-
РЕСЦЕИНОВ ДЛЯ ИСПОЛЬЗОВАНИЯ В
КЛИК-РЕКАЦИЯХ.
Селин Р.1,2, Черний В.1, Мохир А.3
1Институт общей и неорганической химии
им. В.И.Вернадского НАН Украины, просп.
академика Палладина, 32-34, Киев, 03142,
Украина.
2Принстонские лаборатории биомолекуляр-
ных исследований, Украина, ул. Мурманская,
1, Киев, 02094, Украина.
3Университет Фридриха Александра в Эр-
лангене-Нюрнберге, факультет химии и
фармацевтики, кафедра органической химии
II, Хенкештрассе 42, 91054 Эрланген, Герма-
ния.
*е-mail:
selin.roman.oleksandrovich@gmail.com
Розработано методологию синтеза модифи-
цированых флуоресцеинов для использова-
ния в клик-реакциях. Были улучшены выхо-
ды описанных стадий синтеза и оптимизиро-
ваны способы выделения и очистки конеч-
ных и промежуточных соединений.
К л ю ч е в ы е с л о в а: флуоресцеин, ази-
дзамещенный флуоресцеин, клик реакция.
REFERENCES
1. Rostovtsev, V.V.; Green, L.G.; Fokin, V.V.;
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J. Org. Chem., 2002, 67 (9): 3057–3064.
3. Jan-Philip Meyer; Pierre Adumeau; Jason S.
Lewis; Brian M. Zeglis. Bioconjugate Chem,
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4. M. Sameiro T. Gonçalves; Chem. Rev. 2009,
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5. Prakasam T.; Dariusz M.; Krzysztof J., Chem.
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Надійшла 28.01.2020
mailto:selin.roman.oleksandrovich@gmail.com
|
| id | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-131 |
| institution | Ukrainian Chemistry Journal |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-23T01:01:57Z |
| publishDate | 2020 |
| publisher | V.I.Vernadsky Institute of General and Inorganic Chemistry |
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| resource_txt_mv | ucjorgua/95/99f1c69a9cf4a2463a96e209e5476d95.pdf |
| spelling | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-1312026-07-22T08:23:42Z SYNTHESIS OF MODYFIED FLUORESCEINE FOR CLICK REACTIONS СИНТЕЗ МОДИФИЦИРОВАННЫХ ФЛУОРЕСЦЕИНОВ ДЛЯ ИСПОЛЬЗОВАНИЯ В КЛИК-РЕКАЦИЯХ СИНТЕЗ МОДИФІКОВАНИХ ФЛУОРЕСЦЕЇНІВ ДЛЯ ВИКОРИСТАННЯ У КЛІК-РЕАКЦІЯХ Selin, Roman Chernii, Viktor Mokhir, Andriy modified fluorescein, fluorescein, click reaction Reactions of azide-alkilic cycloaddition are well known since 1893. At the same time, with the elaboration of click chemistry, the techniques of labelling biological objects, particularly by fluorescent dyes, were widely developed. The use of fluorescent labels provides the ability to visually monitor the process streamlines hardware load and reduces research time. Fluorescein is among the fluorophores mostly used for labelling of biomolecules due to its high quantum yields and good stability in biological media. However, despite of commercial availability of fluorescein derivatives functionalized for use in click reactions, methods for their synthesis are virtually absent in the literature. Therefore, we have developed a reliable and effective methodic for the synthesis of functionalized fluoresceines for the use in the click reactions. Synthesis of diacetyl N-(4-azidobutyl)-fluoresceine-5(6)-carboxamide was performed in six stages, starting form resorcinol and trimellitic acid anhydride. The diacetylated analogue was synthesized for the click modifications in the “soft” conditions, since N-(4-azidobutyl)-fluorescein-5(6)-carboxamide is poorly soluble in the classic organic solvents. Proposed synthetic protocol allows to increase the yield of the final and intermediate compounds and to optimized the procedure of their isolation and purification. V.I.Vernadsky Institute of General and Inorganic Chemistry 2020-04-07 Article Article Inorganic Chemistry Неорганическая химия Неорганічна хімія application/pdf https://ucj.org.ua/index.php/journal/article/view/131 10.33609/0041-6045.86.3.2020.3-8 Ukrainian Chemistry Journal; Vol. 86 No. 3 (2020): Ukrainian Chemistry Journal; 3-8 Украинский химический журнал; ##issue.vol## 86 ##issue.no## 3 (2020): Украинский химический журнал; 3-8 Український хімічний журнал; Том 86 № 3 (2020): Український хімічний журнал; 3-8 2708-129X 2708-1281 en https://ucj.org.ua/index.php/journal/article/view/131/83 Copyright (c) 2020 Roman Selin, Viktor Chernii, Andriy Mokhir https://creativecommons.org/licenses/by-nc/4.0 |
| spellingShingle | Selin, Roman Chernii, Viktor Mokhir, Andriy СИНТЕЗ МОДИФІКОВАНИХ ФЛУОРЕСЦЕЇНІВ ДЛЯ ВИКОРИСТАННЯ У КЛІК-РЕАКЦІЯХ |
| title | СИНТЕЗ МОДИФІКОВАНИХ ФЛУОРЕСЦЕЇНІВ ДЛЯ ВИКОРИСТАННЯ У КЛІК-РЕАКЦІЯХ |
| title_alt | SYNTHESIS OF MODYFIED FLUORESCEINE FOR CLICK REACTIONS СИНТЕЗ МОДИФИЦИРОВАННЫХ ФЛУОРЕСЦЕИНОВ ДЛЯ ИСПОЛЬЗОВАНИЯ В КЛИК-РЕКАЦИЯХ |
| title_full | СИНТЕЗ МОДИФІКОВАНИХ ФЛУОРЕСЦЕЇНІВ ДЛЯ ВИКОРИСТАННЯ У КЛІК-РЕАКЦІЯХ |
| title_fullStr | СИНТЕЗ МОДИФІКОВАНИХ ФЛУОРЕСЦЕЇНІВ ДЛЯ ВИКОРИСТАННЯ У КЛІК-РЕАКЦІЯХ |
| title_full_unstemmed | СИНТЕЗ МОДИФІКОВАНИХ ФЛУОРЕСЦЕЇНІВ ДЛЯ ВИКОРИСТАННЯ У КЛІК-РЕАКЦІЯХ |
| title_short | СИНТЕЗ МОДИФІКОВАНИХ ФЛУОРЕСЦЕЇНІВ ДЛЯ ВИКОРИСТАННЯ У КЛІК-РЕАКЦІЯХ |
| title_sort | синтез модифікованих флуоресцеїнів для використання у клік-реакціях |
| topic_facet | modified fluorescein fluorescein click reaction |
| url | https://ucj.org.ua/index.php/journal/article/view/131 |
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