6-Polyamino-substituted quinolines: Synthesis and multiple metal (CuII, HgII and ZnII) monitoring in aqueous media

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6-Polyamino-Substituted Quinolines: Synthesis and Multiple

Metal (Cu^II, Hg^IIand Zn^II) Monitoring in Aqueous Media

Received 00th January 20xx,

Accepted 00th January 20xx

Anton S. Abel,*^aAlexei D. Averin,^a,bAndrey V. Cheprakov,^aVitaly A. Roznyatovsky,^aFranck Denat,^c

Alla Bessmertnykh-Lemeune*^cand Irina P. Beletskaya*^a,b

DOI: 10.1039/x0xx00000x

Chemoselective palladium-catalyzed arylation of polyamines with 6-bromoquinoline has been explored to prepare

chelators for detection of metal cations in aqueous media. The introduction of a single aromatic moiety in non-protected

polyamine molecules was achieved using the commercially available Pd(dba)₂/BINAP precatalyst to afford nitrogen

chelators, in which aromatic signalling unit is directly attached to the polyamine residue. Water-soluble receptors were

then synthesized using N-alkylation of these polyamines by hydrophilic coordinating residues. By combining rich

photophysical properties of the 6-aminoquinoline unit with a high coordination affinity of chelating polyamines and a

hydrophilic character of carboxamido-substituted phosphonic acid diesters in a single molecular device, we synthesized

chemosensor 5 for selective double-channel (UV–vis and fluorescence spectroscopies) detection of Cu^IIions in aqueous

media at physiological levels. This receptor is suitable for the analysis of drinking water and fabrication of paper test strips

for the naked-eye detection of Cu^IIions under UV-light. By increasing the number of donor sites we also obtained

chemosensor 6 which is efficient for the detection of Hg^IIions. Moreover, chemosensor 6 is also suitable for multiple

detection of metal ions because it chelates not only Hg^IIbut also Cu^IIand Zn^IIions displaying different responces of

emission in the presence of these three cations.

level. The prolonged exposure of humans to even very low

concentrations of Hg^IIcan lead to neurological diseases, various

cognitive and motion disorders, damage to the prenatal brain,

digestive system and kidney. The maximal level established by the

US Environment Protection Agency (EPA) for the content of this ion

in drinking water is as low as 2 ppb (0.01 µM).³

In turn, zinc(II) and copper(II) are vital trace elements, the

second and third most common in humans, respectively, and

detection and imaging of these ions in biosamples are of significant

interest. Zinc plays an indispensable role in various biological

processes such as gene transcription, regulation of metalloenzymes,

cell apoptosis, neural signal transmission, and insulin secretion, to

name a few.⁴However, the level of zinc ions in the living system

should be carefully controlled because many severe neurological

diseases, including cerebral ischemia, Alzheimer's disease, and

epilepsy are associated with abnormal Zn^IIlevels.⁵

Introduction

The development of sensitive and selective fluorescent

chemosensors for application in analytic chemistry, life sciences,

clinical diagnostics and environmental monitoring is an important

research target of chemical analysis.¹Besides the search for

efficient molecular probes for alkali and alkali-earth metal ions,

much attention has been focused on the design of small molecule

indicators for d-block metal ions which should allow their efficient

monitoring in industrial processes, medical analysis and toxicology,

environmental and household tests.

Among the targeted hazardous metal derivatives, inorganic

mercury(II) species have attached particular attention due to their

high toxicity.²Over the past hundred years, the amount of mercury

in the upper 100 m layer of the world ocean has doubled. The

mercury content in fish, human hair, and other biological specimens

around the world is regularly reported to exceed the permitted

Copper(II) is also found in many metalloenzymes, as this metal

is involved in blood formation, synthesis of hemoglobin,

cytochrome, and gene expression. However, uncontrolled overloads

of this element can cause serious neurodegenerative diseases.⁶

Accordingly, this metal ion is also listed by EPA among toxic

substances, which should be controlled in drinking water, and its

action level is fixed at 1.3 ppm (20 µM).³

When released in the environment both Zn^IIand Cu^IIbecome

harmful for most living organisms.⁷For example, excess of Zn^IIions

may reduce the soil microbial activity and cause phytotoxic effects.⁸

Therefore, many researches were focused on the synthesis of

sensors, which can detect and, in some cases, sequestrate these

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three metal ions in different environment including solutions in synthesis and application of 6-aminoquinolines for d_Vo_ieu_wbl_Ae_rt-_ic_clh_ea_On_nn_line_el

aqueous media under physiological conditions.⁹Recently, the focus detection or signalling multiple metal ions.

DOI: 10.1039/C9OB00259F

was moved to the development of multi-signalling (multi-channel)

Aminoquinolines have attracted considerable attention in

and/or multiple metal chemosensors which save time and effort for fluorescent sensing due to their rich photophysical properties,

the synthesis of the sophisticated molecular probes.¹⁰By using photostability, non-toxicity for non-cancer cells and high membrane

multi-modal signalling several Yes or No combinations are permeability.^9a,13Depending on the position of amino group in

potentially possible leading to several signalling patterns. Different quinoline rings, and structural parameters of the receptor unit,

analytes can switch on different signalling channel, giving a these compounds can afford photochemical molecular devices,

possibility to multiple accumulation of information. Therefore, which detect the presence of metal ions according to different

multi-modal receptors are expected to show an enhanced mechanisms such as photon-induced electron transfer (PET),¹⁴

selectivity and anti-interference ability, to increase the detection internal charge transfer (ICT),¹⁵fluorescence resonance energy

reliability and simplify quantitative measurements. Using these transfer (FRET),¹⁶excited-state intramolecular proton transfer

detectors should also provide an increase in a working range of (ESIPT) ¹⁷and excimer formation.^16,18Thus, these compounds seem

metal ion concentrations as chromogenic, luminescent and to be well suited to develop multiple-metal and multi-modal

electrochemical signalling events are observed at different chemosensors. Surprisingly, only 8-aminoquinolines¹⁹have been so

concentration levels of the analyte. However, the reported far widely investigated in this area, with most of the reported

molecular probes suffer from serious limitations, such as laborious studies being devoted to Zn^IIions sensing.²⁰The potential of other

synthesis, low sensitivity, lack of selectivity, low water solubility, positional isomers of the aminoquinolines for sensing various

operational complexity and difficulties in real-time monitoring. analytes scarcely explored and understood.^15a,18,21

Therefore, the development of optical detection methods, ranging

In this work we chose to explore polar 6-aminoquinolines which

from simple semi-quantitative to highly precise and sensitive ones is are interesting due to their ICT character (heterocyclic nitrogen

required for the efficient analysis of different metal cations under atom serves as an electron acceptor while the amino group is an

real-life conditions.

electron donor), the emission in visible region, low toxicity and

The development of chemosensors is laborious and time- good photostability.²²Despite the long-lasting interest to 6-

consuming. Once the fluorophore unit has been chosen, a series of aminoquinolines as fluorescent derivatization agents for the

molecular probes with different ionophores need be prepared analysis of mono- and oligosacharides²³and fatty acids,²⁴signalling

because solubility and coordination properties of the ligands are reagents for C–C bond formation²⁵or enzyme activity,²⁶the sensory

difficult to predict. In such a case, synthetic methods allowing to properties of these compounds are less investigated.

synthesize small libraries of molecular probes are useful. For

example, conventional click chemistry reactions were reported as a be

Shiff-base derivatives of 6-aminoquinoline have been found to

ratiometric

fluorescent

pH-sensitive

probes.²⁷

6-

rational synthetic approach to explore polymeric sensors.¹¹We Aminoquinolines bearing carboxamide, urea or thiourea groups

have recently proposed an efficient synthetic strategy to obtain were found to be efficient for monitoring inorganic anions and

water-soluble optical chemosensors (Scheme 1).¹²

nucleoside triphosphates.²⁸In turn, 2-methyl-6-aminoquinolines

According to this approach, the libraries of chromogenic with various N-substituents were proposed as chemosensors for

polyamines can be synthesized from polyamines and aromatic diethylchlorophosphate, a nerve agent mimic.^22c

halides via the chemoselective palladium-catalyzed amination

Two recent examples of the detection of metal ions by 6-

reaction (Step 1) followed by the N-alkylation of the obtained aminoquinoline derivatives are of particular interest. Chemosensor

products with different alkyl halides bearing additional coordination 2 (Fig. 1) was proposed for highly sensitive detection of Al^IIIand Zn^II

sites such as hydrophilic [(2-bromoacetylamino)methyl]phosphonic ions in aqueous media by UV–vis and fluorescence spectroscopies.

acid diethyl ester (1) (Step 2). Taking into account a large substrate However, these ions can be distinguished only by absorption,

scope of the catalytic and N-alkylation reactions, this strategy is because the enhancement of the emission was rather similar for

expected to be efficient for search of novel chemosensors involving both of them.¹⁰ⁱA simple colorimetric receptor 3 in acetonitrile

unusual fluoro- and ionophore units. In this work, we address the solutions exhibited different colour changes in the presence of Hg^II

or Cu^IIions.²⁹Nevertheless, these ions also cannot be identified by

fluorescence spectroscopy because each of them lead to similar

emission quenching. The selectivity of the chemosensor 2 and 3

seems to be rather poor when both studied ions are present in the

same solution.

It is to be noted that 6-amino group was also introduced to

improve the optical response of 4-alkoxy and 4-aminoquinoline

derivatives.³⁰Moreover, oxaazamacrocycles containing 4,6-

diaminoquinoline fragment demonstrated interesting changes of

selectivity when the structure of macrocycle was varied.³¹The

compound 4 was identified as a selective chemosensor for Cu^IIions

in acetonitrile.

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Entry

Polyamine (equiv)

Product

Yield,^b(%)

1^c

75

(10)

2

3

62

40

(3)

In this work, we synthesized a novel type of 6-quinolyl

chemosensors with the electron-donor amino group directly

attached to the heterocycle and the second one separated from the

chromophore by the ethylene spacer (compounds 5 and 6, Fig. 1).

This structural organization of the receptor unit could be profitable

to combine PET and ICT processes within a single sensor system as

it was previously demonstrated for pH,³²anions³³and metal ion³⁴

sensors bearing various fluorophores. Exploring sensory properties

of these compounds, we revealed that chemosensor 5 was suitable

for selective detection of cupric cations in aqueous medium under

physiological conditions by using both UV–vis and fluorescence

spectroscopies (a double-channel chemosensor). In contrast,

chemosensor 6 is useful for the fluorescent detection of Hg^IIions.

Moreover, this compound can fluorimetrically distinguish three

metal ions (Cu^II, Zn^IIand Hg^II) in aqueous media (a three-metal

chemosensor). These are the first examples of 6-aminoquinolines

suitable for selective and sensitive detection of toxic metal ions in

physiological conditions.

(3)

4

5

45

57

(3)

(1)

6^d

37

Results and discussion

Ligand synthesis

The chemoselective palladium-catalyzed heterocoupling of

aromatic halides with non-protected linear polyamines, in which

dioxane on reflux (Table 1). To obtain N-(6-quinolyl)-1,2-

diaminoethane (9a) in 75% yield, the reaction of bromide 7 and 1,2-

diaminoethane (8a) was carried out using 10 equiv of the amine

(entry 1). 6-Chloroquinoline was less reactive compared to bromo

derivative and the product was isolated in only 28%. Linear

polyamines 8b and 8c bearing two or three diaminoethane moieties

afforded the monoarylated products 9b and 9c in lower yields, 62%

and 40%, respectively, with 3 equiv of polyamines employed

(entries 2 and 3). The increase of loading of compounds 8b and 8c

up to 10 equiv did not have any beneficial effect on the product

yield. When triamine 8d with longer alkyl chains was reacted with

bromide 7, the product was formed in 45% yield (entry 4).

Interestingly, tris(2-aminoethyl)amine (8e), known as an excellent

tetradentate chelator of transition-metal ions, afforded 6-

quinolinyl-substituted amine 9e in 57% yield (entry 5), comparable

to that observed in the reaction of bis(2-aminoethyl)amine 8b

only the primary amino groups are reactive, is

a known

methodology (Scheme 1).³⁵When the reaction is carried out in the

presence of excess of polyamine, selective monoarylation of the

latter is observed. This reaction is useful for the synthesis of optical

chemosensors, because polyamines are excellent ionophores and

most of the known signalling units are derived from aromatic

compounds. However, recent studies have shown that the Pd-

catalyzed amination of azaheterocyclic halides is much more

complicated compared to the reaction of aryl halides due to

unfavorable coordination of the heterocyclic nitrogen atom to the

palladium centre which can result in catalyst inactivation.^12b,31,36

Fortunately, the reaction of 6-bromoquinoline (7) with

polyamines 8a–f takes place smoothly under the standard

conditions, in the presence of commercially available precatalyst

Pd(dba)₂/BINAP (4/4.5 mol %) and sodium tert-butoxide in 1,4-

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H₂O (pH = 7.4)

CH₃CN

λ_abs, nm

λ_ex,

Ligand

5

λ_em

,

λ_em

,

(ε, cm^-1M^-1) nm

Φ^a

nm

285 (4900),

356 (3200)

356

350

467, 0.012

554

430

434

0.30

6

289 (5000),

356 (3200)

467, 0.017

554

0.36

0.27

10

288 (5600),

350 (3000)

516

0.013

(entry 2). The arylation of azamacrocycle 8f bearing an external

primary amino group gave the product only in 37% yield even when

the Pd(dba)₂/BINAP catalyst loading was increased up to 8/9 mol%

presumably due to high metal-chelating affinity of the

tetraazamacrocycle (entry 6). To note, this reaction can be

conducted using a stoichiometric amount of the expensive amine 8f

because this polyamine molecule contains a single primary amino

group.

Accordingly, the scope of the reaction is quite broad and the

monoarylated products can be obtained in good yields which

sometimes exceeded 50 %. Cu-catalyzed reaction of non-protecting

polyamines with 6-bromoquinoline was reported previously,³⁷but

the selectivity of this coupling was found to be low and depend on

the structure of the amines presumably due to the complexation of

copper ions with polyamine chelators. In contrast, the Pd-catalyzed

approach is useful for the synthesis of novel molecular probes. For

example, compounds 9a–f are of particular interest for assaying

metal ions in aqueous solutions as nitrogen atoms of the polyamine

chain can be further modified in view of adjusting coordination

properties and enhancing sensors solubility in aqueous media.

Moreover, the high reactivity of primary and secondary amino

groups should provide a selective functionalization of these sites in

the presence of the less reactive bulky aromatic amino group and

the nitrogen atom of quinoline residue. In this work, the N-

alkylation reaction was investigated to prepare novel hydrophilic

multidentate chelators.

equiv) in boiling acetonitrile using K₂CO₃as base, the target product

6 was isolated in only 26% yield. After optimizing the reaction

conditions (use of DIPEA instead of potassium carbonate and

running the reaction in chloroform at 40 °C), the product yield

increased in this case to 42%. Under the similar conditions, the N-

alkylation of diamine 9a with bromide 1 (2.2 equiv) afforded

compound 5 in 50% yield. However, the reaction of 1 (4.4 equiv)

with polyamine 9e bearing a tertiary amino group was too

complicated and led to an inseparable mixture of tri-, tetra- and

penta-functionalized derivatives.

Next, we obtained compound 10 containing two 2-picolyl

fragments. This reaction also suffered from side-reactions and

overalkylation. After optimization of the reaction conditions, the

best yield (38%) was obtained when the reaction was performed in

boiling acetonitrile in the presence of DIPEA and potassium iodide

as shown in Scheme 3.

All the new compounds were unambiguously characterized by

NMR, ESI-MS, IR spectra and obtained spectral data were in good

agreement with the assigned structures (see ESI).

Spectroscopic studies of ligands

Phosphonate-substituted derivatives 5 and 6 were soluble in

water at pH 1–12 and in 0.03 M HEPES solution under physiological

conditions (pH = 7.4). In contrast, quinoline 10 was insoluble in neat

The parent polyamines 9a, 9b and 9e were first reacted with

diethyl ((bromoacetylamino)methyl)phosphonate (1) (Scheme 2). In

each reaction, we used as many equivalents of bromide 1 as

required for the transformation of all aliphatic amino groups into

tertary amine sites. However, classical N-alkylation reaction is well

known for low selectivity due to competing overalkylation

affording quarternary ammonium salts, which obviously lowered

the yields of the target derivatives. The simplicity of procedure and

ease of separation of side quarternary salts could outweigh this

drawback. When triamine 9b was reacted with bromide 1 (3.3

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water. To obtain its aqueous solutions for spectroscopic the chelator by “tuning” of the structure is quite important for

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investigations, a stock solution of the ligand in methanol was chemosensor development.

prepared and diluted by water or the HEPES buffer by up to 50

times (2 vol% of methanol remained in the final solutions).

The protonation of ligands 5, 6 and 10 in aqueous solutions in a

range of pH values was investigated by UV–vis and fluorescence

The spectroscopic data of polyamines 5, 6 and 10 in 0.03 M spectroscopies. Titrations of compounds 5 and 6 were conducted in

HEPES solution are summarized in Table 2. water, while the addition of a small amount of methanol (up to 6

The absorption spectra of compounds 5 and 6 were almost vol% of MeOH) was necessary in the measurements of compound

identical and show bands characteristic of 6-aminoquinoline 10 because of its limited solubility in neat water.

chromophore with absorbance maxima at 288 and 350 nm (Fig.

Both absorption and emission of studied compounds

2).^22aThe maximum of the low-energy band was blue-shifted in the progressively changed on gradual addition of hydrochloric acid. The

spectrum of compound 10 by 6 nm. We assumed that it is caused spectral changes were rather similar for all compounds and

by partial protonation of compound 10 in the studied solution that representative UV–vis and fluorescence-based titrations of

was further proven by detailed studies of the ligand protonation compound 5 are depicted in Fig. 3A and 3B, respectively. As shown

(see below).

in Fig. 3A, a broad absorption band was observed in basic media

The emission of 10⁻⁵M aqueous solution of these compounds (λ_max= 355 nm). The addition of hydrochloric acid results first in the

was quite low and covered a wide spectral region from 400 to 600 red shift of maximum to 411 nm until pH = 3.5, and then to smaller

nm. Two bands were observed in each spectrum being better blue shift to 395 nm at higher acidities, pH lower than 2.

resolved in the spectrum of compound 5 (Fig. S1). The shape of

To determine apparent protonation constants, numerical data

bands and quantum yields were not dependent on concentration fitting was performed using the Specfit program.³⁸The obtained

within the limits of experiment that is indicative of the absence of values are compiled in Table 3 together with the literature data for

aggregation phenomena and excimer formation.

the earlier reported chemosensors 11–13 involving similar

ionophore units (Fig. 4).

Protonation of ligands

The best fits were obtained when the UV–vis titration curves

2+

were processed with

a

3-species model (L–LH⁺–LH₂

)

for

Polyamines are known as excellent chelators for metal ions, and

they are widely explored as ionophores in optical chemosensors.¹

However, due to rather high basicity polyamines undergo partial

protonation when used in aqueous media. This process

sophisticates the interpretation of data on complexation of metal

ions, and should be explicitly taken into consideration.³²Thus,

providing of the balance between basicity and complexing ability of

polyamines 5 and 6, and a 4-species model (L– LH⁺–LH₂²⁺–LH₃³⁺) for

picolyl-substituted compound 10. Titration curves and distribution

diagrams, simulated electronic absorption spectra of all studied

compounds and their protonated forms calculated using the Specfit

program are shown in Fig. S2–S13 (ESI†).

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Ligand

5^b

Method

pKa(N_q)

pKa(N_t)

pKa(N_p)

(FL)^e

(UV–vis)^f

(FL)^e

5.60(5)

2.23(1)

–

5.64(1)

6.2(1)

5.51(4)

5.18(6)

5.25(9)

–

2.26(4)

4.38(2)

4.4(1)

–

6^b

–

(UV–vis)^f

(FL)^e

–

3.91(3)

3.2(3)

–

10^b

6.82(7)

6.8(2)

(UV–vis)^f

(PT)^h

11^c

12^c

13^d

2.11(1)

4.39(3)

6.96(1)

–

-

–

3.81(3)

agreement with the structure of diprotonated species proposed

during the interpretation of UV–vis data (Scheme S2).

The calculated absorption spectra of polyamine 10 and its

monoprotonated form [10H]⁺are similar (Fig. S12). Thus, the first

proton should mainly reside on the tertiary nitrogen atom (N_t)

which is the most basic, being the most distant from 6-

aminoquinoline chromophore (Scheme S3). The second protonation

resulted in batochromic shifts and hyperchromic change of the

absorption band, suggesting protonation affecting the quinoline

nitrogen atom (N_q). In the third step, the pyridine nitrogen atoms

(N_p) are protonated, leaving the chromophore almost unaffected as

evidenced by close resemblance of the absorption spectra of

[10H₂]²⁺and [10H₃]³⁺.

In the visible region of fluorescence spectra of ligands 5, 6 and

10, two very broad emission bands were observed under basic

conditions (Figs. 3B, S18 and S22). When pH was decreased from 11

to 7 by adding hydrochloric acid, the spectral changes were small.

However, acidification of the solution towards pH = 3–4 leads to a

disappearance of the higher-energy band (467 nm for 5) with

simultaneous increase of the intensity of the second band (554 nm

for 5). Then a blue shift of the emission band maxima (536 nm for 5)

was observed and the maximal degree of "turn-on" observed on

further acidification of the solution. Thus, the examination of pH

dependence of fluorescence spectra of these compounds showed

switching on of emission upon protonation of the side-chain amine

presumably as a result of thermodinamically less favorable PET

process involving the side nitrogen atom (N_t) separated from

aminoquionline fragment by two methylene units.³²Moreover, the

shape of the emission spectrum and the positions of the maxima

The protonation sequence can be unambiguously established

based on electronic absorption data (Schemes S1 and S2, Figs. S4

and S8). Moreover, the lower basicity of tertiary nitrogen atoms in

carboxyamide-substituted polyamines 11 and 12 was previously

reported.³⁹In agreement with these data, the protonation

sequence of compounds 5 and 6 starts from the quinoline nitrogen

atom (N_q) that induces a large bathochromic shift of the absorption

maximum of compounds 5 and 6. The next proton is likely to go to

the tertiary nitrogen atom (N_t) bearing lesser number of electron-

withdrawing carbamoylmethyl substituents. This protonation step is

observed at significantly different pH for compounds 5 and 6, in full

agreement with higher basicity of nitrogen with a single electron-

withdrawing substituent, as compared to the atom bearing two of

such. However, spectral changes corresponding to this step are

small and similar for both compounds because the protonation of

nitrogen atoms remote from the chromophore very slightly affects

the absorption properties of the compounds.

The assignment of the protonation sites of ligand 6 was also

1

confirmed by H and ³¹P{¹H} NMR experiments (Fig. S26 and S27).

First, the ¹H and ³¹P{¹H} NMR spectra of 0.04 M solution of

polyamine 6 in a D₂O/MeOH-d₄mixture (5:1) were recorded, and all

proton signals were assigned. Then, this solution was acidified to pH

1

= 2 and H and ³¹P{¹H} NMR spectra were recorded again. Spectral

changes in proton and phosphorous chemical shifts were in a good

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Thus, compounds 5, 6 and 10 can be regarded as suitable dyes

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for spectroscopic monitoring of pH. Moreover, the protonation of

all studied chelators is observed only at pH < 8 due to electron-

withdrawing character of substituents attached to the aliphatic

amino groups. The lower basicity of these compounds is favourable

for the study of binding metal cations in aqueous media, in which

the competitive protonation of the ligand is an unfavourable

sophistication. From this point of view, the valuable property of the

carboxyamide substituent compared to the 2-pinacolyl fragment is

its ability to decrease the pK_avalues of the binding pockets thereby

extending the pH interval favourable for binding metal ions up to

physiological conditions.

Detection of metal cations

The sensing properties of receptors 5, 6 and 10 were evaluated

by UV–vis and fluorescence spectroscopy. The spectra were

recorded before and after addition of excess (5 equiv) of 15 metal

perchlorates to aqueous solutions of the ligands at pH = 7.4

maintained with HEPES buffer.

Ligand 10 in which the diamine chain is functionalized by two 2-

picolyl residues exhibits low selectivity with respect to

environmentally-relevant metal ions. Remarkable absorbance

changes were observed after addition of Zn^II, Cd^II, Cu^II, Cd^II, Co^IIand

Ni^IIions to the ligand solution (Fig. S28). Emission of the ligand also

changed in the presence of these cations (Fig S29). Our attempts to

increase the chelator selectivity by switching from HEPES to acetate

buffer (pH = 5.0) where 10 exists in protonated forms (Fig S13)

failed. In acetate buffer, the spectral response was observed for

nine different cations as shown in Fig. S30 and S31.

change during the titration that presumably indicates a significant

contribution of the emission according to internal charge transfer

(ICT) mechanism. Excited species in this case are highly responsive

to protonation of the quinoline nitrogen atom and intramolecular

hydrogen bonding of the aromatic 6-amino group.

The respective apparent protonation constants were estimated

using the Specfit program (Figs. S18–S25). As in the UV–vis

2+

titrations, the 3-species model (L–LH⁺–LH₂

) was used for

polyamines 5 and 6 and a 4-species model (L–LH⁺–LH₂²⁺–LH₃³⁺) for

picolyl-substituted derivative 10. The obtained values of the

constants are reported in Table 3. These values are in a good

agreement with those derived from spectrophotometric titrations.

As shown in Fig. 5 for compound 5, the colour of the ligand

solution changes at pH = 3–4 after the protonation of quinoline

nitrogen. This change can be observed by naked eye and is

particularly well visible under UV-light, when the colour of emission

serves as a backlit background for the observation of yellow tint of

solution.

Sensing properties of diamine 5 differ from those of chelator

10. Spectral investigations of the solutions before and after addition

of 15 different metal perchlorates showed remarkable

hypsochromic shifts of absorption bands of chemosensor 5 only

after addition of Cu^IIions (Fig. 6 and S32).

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Copper(II) ions can also be distinguished from other metal absorption spectra and distribution diagrams are displayed in

cations due to the fluorescence quenching which can be observed Figs. S35 and S36. A similar value of stability constant (logK₁₁= 5.57)

either visually or using a laboratory fluorometer (Fig. 6B). Although was obtained by using a fluorescence titration data. The calculated

certain changes (less than 20%) of the emission intensity were emission spectra and distribution diagrams of the ligand 5 and the

effected by many metal ions, a strong and readily observable complex are shown in Figs. S38 and S39.

quenching of the emission (up to 80%) was noticed only in the The limit of detection (LOD) of Cu^IIions has been determined by

presence of copper(II) ions. Competitive binding studies revealed UV–vis and fluorescence spectroscopies using the 3σ method.⁴¹

that Cu^IIcould be effectively detected in the presence of other Using a laboratory fluorometer, up to 0.3 µM of Cu^IIions can be

metal ions including Ag^I, Hg^II, Cd^II, Pb^II, Ni^II, Zn^II, Cd^IIat least when detected

what

is

significantly

lower

compared

to

the concentration level of these metals is the same as that of Cu^IIspectrophotometric LOD which was found to be of 9 µM. The action

ions (Fig. 7). This selectivity can be explained by a higher affinity of level of Cu^IIions in drinking water is fixed at 20 µM by EPA. Thus,

ligand 5 to copper(II) ions compared to other metal ions because ligand 5 is suitable for the analysis of drinking water by both optical

the observed response is independent on time.

detection methods. The choice of the method for the analysis of a

The stability constant of Cu^IIcomplex was determined by real sample is determined by the concentration of the Cu^IIions and

spectrophotometric and fluorimetric titrations of 5 with copper(II)

perchlorate (Fig. S34 and 37). When Cu^IIamount was gradually

increased to 1.3 equiv, isobestic points were observed in the

titration curves suggesting that only one spectrally distinct complex

was formed in the studied solution. Numerical data processing was

performed with Specfit program and the best fit was obtained when

the titration curves were approximated by a 2-species (L–CuL)

model to afford the value of logK₁₁= 5.85. The calculated electronic

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the presence of other ions and small molecules which can

perturbate the optical response of the chemosensor.

Сhelator 5 appeared more sensitive and selective than the

sensor 3 which is the only 6-aminoquinoline-derivative reported

earlier for detection of Cu^II. Moreover, chelator 5 provides

detection in aquatic media at physiological pH while chemosensor 3

was reported for sensoring in acetonitrile.

We also prepared paper test-strips charged with the ligand 5 by

wetting of filter papers with a CH₂Cl₂solution of the ligand and

drying them on air. Under UV-light, these strips enable a fast semi-

quantitative determination of Cu^IIions at the ppm level and also can

be used for the analysis of drinking water (Fig. 8).

The presence of the additional tertiary amine group in the

molecule of the ligand 6 results in an increase of denticity and

basicity of the ligand compared to chelator 5. As a result, this ligand

strongly binds not only Cu^IIbut also Hg^IIand Zn^IIcations, which is

evidenced by changes in absorption in the presence of these metals

(Fig. 9).

UV–vis and fluorescence spectroscopies (Figs. S3, 45 and S47).

Isosbestic points were observed in UV–vis titrations within the

whole range of concentrations of added ions. This indicates that the

only one spectrally distinct complex is formed in each of the studied

solutions. However, calculations of the stability constants were

successful only for [Zn(6)]²⁺because stability constants of other

metal complexes were too high to be estimated by direct titration.⁴²

The UV–vis- and fluorescence-based titration data for Zn^IIcomplex

were fitted to a 2-species (L–Zn^IIL) model and the stability constant

of [Zn(6)]²⁺was found to be logK₁₁= 5.1 and 4.78, respectively. The

data for these titration experiments are shown in Figs. S47–S52.

Job's plots based on UV-vis and fluorimetric data⁴³of Hg^IIand Cu^II

complexes showed maxima for 1:1 molar ratio, thus establishing

the 1:1 stoichiometry of complexes ratio in both experiments (Figs.

S43–S46).

The ligand’s emission decreased 5-fold in the presence of Cu^II

ions (Figs. 9 and S43). When Hg^IIions (1 equiv) were added to the

ligand solution, the peak intensity of fluorescence increased by 3.6

times and the maxima of two emission bands exhibited a blue shift

(by 10 and 6 nm, respectively) (Figs. 9 and S45). In contrast, when

the Zn^II/chelator ratio was gradually increased from 0 to 3, the

isoemission point at 487 nm was observed (Fig. 10). Thus, ligand 6

can serve as a ratiometric fluorescent probe for Zn^IIions. The

wavelengths of two maxima is convenient for the ratiometric

measurements. Such a different response of emissive properties of

ligand 6 in the presence of Hg^II, Cu^IIand Zn^IIions could be used for

identification of these ions.

These three metal ions can also be distinguished by using

electronic absorption spectroscopy (Fig. S41). Addition of Hg^II, Cu^II

and Zn^IIsalts leads to remarkable changes in the UV–vis spectrum of

the chelator 6 being specific for each of them. Unfortunately,

addition of other metal ions such as Pb^II, Co^IIand Ni^IIalso influences

the spectrum as shown in Fig. S41.

The investigations of the cross-selectivity of metal ion binding

by fluorescence spectroscopy demonstrated that mercury ions

could be determined in the presence of 14 different metals and

only Cu^IIions strongly interfered with the detection (Fig. 11).

Next, the ligand 6 was titrated with Hg^II, Cu^IIand Zn^II

perchlorates to determine stability constants of their complexes by

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LOD of Hg^IIions was determined by using UV–vis and

Metal binding resulted in substantial spectral changes,

fluorescence techniques according to the 3σ method.⁴¹In the UV– especially in the high field region. Two distinct sets of signals

vis measurements, LOD was found to be of 3.0 µM (600 ppb), which corresponding to the free ligand 6 and complex [Zn(6)]²⁺were

can be significantly improved (40 nM, 8 ppb) using the emission observed in the spectra. When 2 equiv of the metal salt were added

measurements. Switch from UV–vis to fluorescence techniques also to the ligand solution, the ¹H and ³¹P{¹H} NMR spectra revealed the

allows increase the working range of concentrations in which Hg^IIpresence of only a single complex species (Figs. 12 and S54–S60).

ions can be detected by using chemosensor 6.

The proton signal assignment in this complex relies on ¹H–¹H COSY,

It has to be noted, that LOD of Hg^IIions for colorimetric ¹H–¹H NOESY and various NMR experiments with heteronuclear

molecular probe 3, the only one 6-aminoquinoline-based correlations (Table S1, Figs. S59-S67). To precise, using HSQC ¹H and

chemosensor reported previously for analysis of Hg^IIions in ¹³C chemical shifts as well as J_PCcoupling constants were

acetonitrile, was much higher (360 ppb).

established, TOCSY experiment was used for the assignment of the

We also prepared paper test-strips based on the ligand 6 by signals in the triamine chain, NOESY helped to identify carbonyls in

immersing filter papers into a 1.3 mM CH₂Cl₂solution of the ligand amido groups and adjacent methylene groups, while LR-HSQMBC

6 and drying them on air. Under UV-light, aqueous solutions of Hg^II, was helpful in the correlation between phosphorus atoms and

Cu^IIand Zn^IIperchlorates induce slight but quite different hue of the attached chelators. Also the analogies with the reference spectra

indicator fluorescence paper that can be used for qualitative for related polyamine-containing complexes were taken into

determination of these metal ions (Fig S53).

Finally, it is noteworthy that compounds 5 and 6 are likely to

serve as a useful alternative to the commonly used Schiff-base

consideration.³⁹The summary of these data are also depicted in Fig.

12. According to the proton chemical shifts and their splitting

pattern, the coordination environment of the zinc ion is formed by

chemosensors bearing aminoquinoline signalling groups, for chelate rings. The three nitrogen atoms of the polyamine backbone

instance compound 2¹⁰ⁱ. The Schiff-base chemosensors are known

to be unstable under acidic and basic conditions. This instability

together with the three amide groups are likely to be involved in

binding Zn^IIion.

Additional information on the coordinated amide groups was

gained from 1500–1700 cm^-1region of FT–IR spectrum, where the

amide I (ꢀ_C=O= 1669 cm^–1) and amide II (ꢁ_CNH= 1521cm^–1) bands of

the free ligand 6 were observed (Figs. S60). Vibration frequency ꢀ_C=O

is diagnostic for the level of π-electron delocalization, and appear in

1615–1625 cm^–1region for metal-coordinated carbonyl oxygen

induces the necessity to work with freshly prepared solutions or

even more serious problems related to decomposition of

chemosensors during the analysis of real-life samples. The amino-

based chemosensors are more stable and allow avoid this problem.

Structural studies of complexes

atom of amide group.⁴⁴In contrast, the formation of

a

Unfortunately, all our attempts to grow single crystals of

studied complexes for X-ray diffraction analysis were unsuccessful.

However, preliminary structural information on the nature of these

species can be derived from their UV–vis, FT–IR, ¹H and ³¹P{¹H}

NMR spectra. The most unambiguous information was obtained for

[Zn(6)]²⁺complex by means of NMR spectroscopy, because the

signals of the aromatic protons in 6 remained sharp during stepwise

addition of zinc perchlorate allowing for accurate assignment of

signals (Fig. 12).

deprotonated nitrogen-metal bands would result in a shift of ꢀ_=Oup

to 1580 cm^–1partially overlapping with the ꢁ_CNHbending band.⁴⁴In

the studied zinc complex the stretching ꢀ_C=Oband appeared at 1635

cm^–1indicating that the oxygen atom of the amide group was

coordinated to the metal atom.

To gain deeper insights into the structure of complex [Zn(6)]²⁺

and its electronic and photophysical properties DFT studies were

performed. The structure of complex was modelled performing DFT

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calculations using Firefly quantum chemistry package,⁴⁵which is involving all phosphonate groups, revealing that hig_Vh_iely_{w A}p_ro_ticla_ler_OP_nl–_inO_e

partially based on the GAMESS (US)⁴⁶source code. The calculations bonds are quite distant from the quinoline r^Des^Oid^I:u¹e⁰.^{.1039/C9OB00259F}

were performed using B3LYP functional with STO 6-31G(d,p) basis

The elucidation of the coordination environment of Hg^IIions

set for all elements, at each step full optimization of geometry was was much more difficult due to labile character of the complexes.

achieved, and the minima were confirmed by computation of Complex [Hg(6)]²⁺was detected by ESI-HM analysis due to the

vibration frequencies. The modelling was started with computing presence of intensive peak at 566.66049 m/z. Metal binding

the geometry of N-(6-quinolyl)-1,2-diaminoethane complex with Zn^IIproduced also certain spectral changes in high and low field regions

1

ion, and further, the other chelation centers were added one by of H NMR spectrum of the ligand 6 but all proton signals were

one. This procedure gave the expected 6-coordinated Zn complex, broadened when 40 mM solution of the free ligand in D₂O/MeOH-

in which Zn atom was bonded to three amine nitrogen atoms (one d4 (5:1) solvent mixture was titrated with the mercury(II)

aromatic and two aliphatic amine centers), and three oxygen atoms perchlorate (Fig. S60). The proton resonances from methyl groups

of the amide groups. Two possible geometries were thus evaluated, of diethoxyphosphoryl substituents were easily recognized due to

and Fig.13 shows the geometries of backbones of these complexes their characteristic chemical shifts. The increased number of methyl

omitting hydrogen atoms and phosphonate-substituted arms. The signals compared to that observed in the spectrum of ligand 6 and

complexes are deliberately displayed in a way revealing the close complex [Zn(6)]²⁺indicated that at least some of

similarity of coordination environments and chelate rings.

diethoxyphosphoryl groups are bound to Hg^IIions. Upfield shift of

Both geometries are similar to be composed of five chelate the resonance of the aromatic proton H-5 was consistent with a

rings exhibiting no significant steric congestion in any part of the coordination of the metal ion to the heteroarylamine nitrogen

complex; the quinoline residue is bent outward in both complexes atom.

avoiding close contacts with the atoms of the polyamine scaffold.

³¹P{¹H} NMR spectra afforded additional information on the

The main difference of the obtained configurations is in the relative complexes (Fig S60). After addition of 1 equiv of Hg^IIperchlorate,

positions of oxygen and nitrogen coordination centers. In the first three sets of phosphorous signals in approximate ratio of 2:2:1

configuration each oxygen center is opposed by amine nitrogen were observed reflecting the presence of three different complexes

center in trans-geometry. In the second, there are trans-NN and in the solution. Each sets of signals was composed of three equal

trans-OO pairs and a single trans-NO pair. As far as there is no singlets. When the second equivalent of the mercury(II) perchlorate

significant strain involved the difference between these complexes was added to the studied solution, the ratio of the complexes was

is likely to be accounted for by these trans-interactions, making the changed and two major species were observed in the solution. In

second complex marginally more stable (the difference between FT–IR spectrum of the evaporated solution (Hg^II/6 ratio is 2/1), a

computed enthalpies of formation is only 1 kcal/mole in favour of very broad absorption band was observed at 1530–1660 cm^–1that

the second complex) in agreement with slightly shorter bonds (e.g. presumably could indicate that different coordination modes of

the distance between Zn^IIand heteroarylamine nitrogen is 2.10 Å vs amide group are observed in these Hg^IIcomplexes and not all of

2.18 Å, etc.) in the second configuration. Such a close similarity of them are coordinated to the metal centre.

geometries and apparent lack of specific intramolecular

It should be also noted, that only one complex was detected by

interactions, along with marginal difference of energies makes UV–vis and fluorescence spectroscopies in more dilute (20–30 µM)

these both configurations practically indistinguishable by spectral solutions of chelator 6 after addition of the mercury(II) perchlorate.

features, and we believe that both are formed in solutions under Thus, only one of three species detected by ³¹P{¹H} NMR

study. Fig. 14 shows the optimized geometry of the second complex spectroscopy in 0.04 M solution is sufficient stable to be observed

in more diluted solutions by optical methods. Unfortunately, the

of

methyl analogue of Zn complex

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structure of this species cannot be determined by using NMR mass measurements (HRMS ESI) were made using _VT_ieH_wE_AR_rtM_iclO_{e O}L_nlT_inQ_e

DOI: 10.1039/C9OB00259F

spectroscopy due to its labile character.

Orbitrap Elite. Solutions in methanol were used for the analysis.

Paramagnetic character of Cu^IIions also makes the structural Fluorescence spectroscopic studies were performed with HORIBA

analysis of copper(II) complexes formed with ligand 6 difficult. The Jobin Yvon Fluoromax-2 spectrophotometer with

a standard

UV–vis response on Cu^IIbinding should result from the binding of fluorometer cell (Hellma, 111-QS, pathlength 10 mm, chamber

Cu^IIto the heterocyclic nitrogen atom or the aromatic amino group. volume: 3.5 mL). Emission spectra were recorded after excitation at

The blue shift of the absorption maximum presumably indicates the corresponding wavelength (excitation slit = 3 nm and emission

that the heteroarylamine nitrogen is coordinated to the metal slit = 3 nm).

centre. In 1500–1700 cm^-1region of FT–IR spectrum, the two

Fluorescence quantum yields were measured at 25 °C by a

intensive bands are observed in the region of 1680–1600 cm^-1. They relative method using quinine sulfate in 0.05 M H₂SO₄(Φ_F= 54%) as

were assigned to amide I bands of free (1653 cm^-1) and coordinated a standard.⁵⁰The following equation was used to determine the

by the oxygen atom (1624 cm^-1) amide groups. Based on a high relative fluorescence quantum yield:

affinity of Cu^IIions to aliphatic amines and typical coordination

numbers of this metal ion, we can assume that three nitrogen

atoms of the polyamine chain are involved in the complex

formation and two amide groups complete the coordination sphere

of the pentacoordinated metal centre.

ꢅ ∗ ꢆ^ꢄ∗ ꢇ^ꢈ

ꢅ^ꢄ∗ ꢆ ∗ ꢇ_ꢉ^ꢈ

ꢂ_ꢃ= ꢂ_ꢃ^ꢄ

where ꢆ is the absorbance (in the range of 0.01–0.1 a.u.), ꢅ is the

area under the emission curve, ꢇ is the refractive index of the

solvents (at 25 °C) used for the measurements, and the subscript s

represents the standard. The following refractive index values are

used: 1.333 for water and 1.341 for CH₃CN.

Detection of sulfide anions

In view of the known high affinity of sulfide to Cu^IIions, many

non-fluorescent copper complexes involving emissive ligands

Synthesis

exhibit the appearance of fluorescent response in the presence of Synthesis of 8c. The solution of KOH (3.4 g, 61 mmol) in methanol

sulphides, which is quite useful for indirect detection of this anion (25 mL) was added to the solution of 8c•2HCl (1.67 g, 7.62 mmol) in

in aqueous media.^19g,47The complex [Cu(5)]²⁺can also be used for methanol (25 mL). The mixture was stirred for 1 h at room

this purpose as shown in Fig. S76. Addition of excess (50 equiv) of temperature, than 25 mL of dichloromethane was added to the

sulphide to the solution of [Cu(5)]²⁺in 0.03 M HEPES solution (pH = reaction mixture. The solution was filtered, the filtrate was

7.4) led to a remarkable increase in the emission of the solution evaporated under reduced pressure and 50 mL of dichloromethane

(about 4.2 times) which can be observed visually under UV was added to the residue. The solution was again filtered, the

irradiation of the solution.

filtrate was concentrated and dried under under reduced pressure

giving the product as colorless oil. Yield 900 mg (81%). ¹H NMR (400

MHz, CDCl₃): δ = 1.37 (br. s, 6H, NH), 2.64 (t, J = 5.8 Hz, 4H, CH₂NH₂),

2.71 (s, 4H, CH₂NH), 2.77 (t, J = 5.8 Hz, 4H, CH₂NH). ¹³C NMR (100.6

MHz, CDCl₃): δ = 41.7 (2C, CH₂NH₂), 49.3 (2C, CH₂NH), 52.4 (2C,

CH₂NH).

Experimental

Materials and instruments

Unless otherwise noted, all chemicals and starting materials

were obtained commercially from Acros® or Aldrich® and used

without further purification. (1,4,7,10-Tetraazacyclotridecan-5-

yl)methanamine (2f) was kindly provided by CheMatech (France).

[(Bromoacetylamino)methyl]phosphonic acid diethyl ester (1) was

prepared according to published procedure.⁴⁸Pd(dba)₂was

synthesized according to a known method and used without

recrystallization.⁴⁹The solvents were dried according standard

procedures: dioxane was distilled successively over NaOH and

sodium under argon, CH₂Cl₂and CH₃CN were distilled over CaH₂,

chloroform was distilled over P₂O₅. All reactions were performed in

argon.

Palladium-catalyzed amination of 6-bromoquinoline with

polyamines. General procedure. A flask flushed with dry argon and

equipped with a magnetic stirrer and condenser was charged with

6-bromoquinoline (0.5 mmol), Pd(dba)₂(4–8 mol%), the phosphine

ligand (4.5–9 mol%), the appropriate polyamine 2a–f (0.5–5 mmol),

and absolute 1,4-dioxane (5 mL). Sodium tert-butylate (0.75 mmol)

was added, and the mixture was stirred under reflux for 24 h, and

then cooled down to room temperature. Solvent was evaporated

under reduced pressure, and the residue was chromatographed

(silica gel, CH₂Cl₂, then CH₂Cl₂/MeOH, from 200:1 to 3:1, then

CH₂Cl₂/MeOH/NH₃(aq), from 100:20:1 to 10:4:1 v/v).

Column chromatography purification was carried out on silica

gel (40-60 μm, Merck®).

N-(quinolin-6-yl)ethane-1,2-diamine (9a).⁵¹Compound 9a was

obtained from 6-bromoquinoline (104 mg, 0.5 mmol) and 8a (300

mg, 5 mmol) in the presence of Pd(dba)₂(12 mg, 4 mol%) and

BINAP (14 mg, 4.5 mol%). Yield: 70 mg (75%); yellowish oil;

chromatography (silica gel, CH₂Cl₂/MeOH/NH₃(aq), 100:20:1 v/v).

¹H NMR (400 MHz, CDCl₃): δ = 1.73 (br. s, 2H, NH₂), 3.02 (t, J = 5.5

Hz, 2H, CH₂NH₂), 3.28 (t, J = 5.5 Hz, 2H, CH₂NQ), 4.46 (br. s, 1H,

NHQ), 6.70 (d, J = 2.5 Hz, 1H, H5(Q)), 7.13 (dd, 1H, J = 9.0 Hz, J =

2.5 Hz, 1H, H7(Q)), 7.25 (dd, J = 8.3 Hz, J = 4.2 Hz, 1H, H3(Q)), 7.86

(d, J = 9.0 Hz, 1H, H8(Q)), 7.90 (dd, J = 8.3 Hz, ⁴J = 1.5 Hz, 1H, H4(Q)),

8.59 (dd, J = 4.3, ⁴J = 1.5 Hz, 1H, H2(Q)). ¹³C NMR (100.6 MHz,

UV–vis spectra were obtained with Varian Cary 60

spectrophotometer by using a rectangular quartz cell (Hellma, 111-

QS, pathlength 10 mm, chamber volume: 3.5 mL). NMR spectra

were acquired using Bruker Avance 400 MHz and Agilent 400MR

spectrometers and referenced to solvent residual protons. MALDI-

TOF mass-spectra were obtained with Bruker Daltonics Autoflex II

mass-spectrometer in positive ion mode with dithranol matrix and

polyethyleneglycols as internal standards. FT–IR spectra were

registered with FT-IR Nexus (Nicolet) and Bruker Vector 22

spectrophotometers with Micro-ATR accessory (Pike). Accurate

4

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CDCl₃): δ = 40.5 (1C, CH₂NH₂), 45.8 (1C, CH₂NQ), 102.8 (1C, C7(Q)), 2H, CH₂CH₂CH₂), 2.06 (br. s, 3H, NH, NH₂), 2.71 (t, J_V=_iew6_A.9_rticH_lez_O, _n2_liH_ne,

121.3 (1C, CH(Q)), 121.6 (1C, CH(Q)), 129.8 (1C, CH(Q)), 130.1 (1C, CH₂N), 2.78 (t, J = 6.5 Hz, 4H, CH₂N), 3.28 (t^D, J^O=^I:5¹⁰.5^.10H³z⁹,^/2^CH^9O, C^BH⁰⁰₂N²⁵Q⁹)^F,

C4a(Q)), 133.9 (1C, CH(Q)), 142.8 (1C, C6(Q)), 145.8 (1C, C2(Q)), 4.90 (br. s, 1H, NHQ), 6.65 (d, ⁴J = 2.5 Hz, 1H, H5(Q)), 7.07 (dd, 1H, J

146.3 (1C, C8a(Q)). HRMS (ESI): m/z calc. for C₁₁H₁₄N₃: 188.1188; = 9.1 Hz, ⁴J = 2.5 Hz, 1H, H7(Q)), 7.24 (dd, J = 8.2 Hz, J = 4.2 Hz, 1H,

found: 231.1186 [M+H]⁺.

H3(Q)), 7.83 (d, J = 9.1 Hz, 1H, H8(Q)), 7.88 (d, J = 8.2 Hz, 1H, H4(Q)),

8.58 (dd, J = 4.2, ⁴J = 1.5 Hz, 1H, H2(Q)). ¹³C NMR (100.6 MHz,

CDCl₃): δ = 28.8 (1C, CH₂CH₂NQ), 33.3 (1C, CH₂CH₂NH₂), 40.4 (1C,

CH₂NH₂), 43.0 (1C, CH₂NQ), 47.9 (1C, CH₂NHCH₂), 48.5 (1C,

CH₂NHCH₂), 102.4 (1C, C7(Q)), 121.3 (1C, CH(Q)), 121.5 (1C, CH(Q)),

130.1 (1C, CH(Q)), 130.2 (1C, C4a(Q)), 133.6 (1C, CH(Q)), 143.1 (1C,

C6(Q)), 145.8 (1C, C2(Q)), 146.5 (1C, C8a(Q)). HRMS (MALDI-TOF):

m/z calc. for C₁₅H₂₃N₄: 259.1923; found: 259.1971 [M+H]⁺.

N-[2-(quinolin-6-ylamino)ethyl]ethane-1,2-diamine

(9b).

Compound 9b was obtained from 6-bromoquinoline (104 mg, 0.5

mmol) and 8b (155 mg, 1.5 mmol) in the presence of Pd(dba)₂(12

mg, 4 mol%) and BINAP (14 mg, 4.5 mol%). Yield: 71 mg (62%);

yellowish oil; chromatography (silica gel, CH₂Cl₂/MeOH/NH₃(aq),

100:20:1 v/v). n_max/cm^-13295br (NH), 3056m, 2939m, 2881w,

2849w, 2828w, 1657s, 1623s, 1509m, 1467m, 1436m, 1382m,

N-(2-aminoethyl)-N-[2-(quinolin-6-ylamino)ethyl]ethane-1,2-

1361m, 1245m, 1180m, 1152m, 1124m, 1106m, 1025m, 830m,

1

791m, 768m, 648m, 624m, 474m. H NMR (400 MHz, CDCl₃): δ = diamine (9e). Compound 9e was obtained from 6-bromoquinoline

2.05 (3H, br. s, NH, NH₂), 2.71 (t, J = 5.7 Hz, 2H, CH₂N), 2.82 (t, J = (104 mg, 0.5 mmol) and 8e (220 mg, 1.5 mmol) in the presence of

5.7 Hz, 2H, CH₂N), 2.93 (t, J = 5.7 Hz, 2H, CH₂N), 3.28 (t, J = 5.7 Hz, Pd(dba)₂(12 mg, 4 mol%) and BINAP (14 mg, 4.5 mol%). Yield: 74

4

2H, CH₂NQ), 4.64 (br. s, 1H, NHQ), 6.68 (d, J = 2.5 Hz, 1H, H5(Q)), mg (57%); yellowish oil; chromatography (silica gel,

7.12 (dd, 1H, J = 9.0 Hz, ⁴J = 2.5 Hz, 1H, H7(Q)), 7.23 (dd, J = 8.3 Hz, J CH₂Cl₂/MeOH/NH₃(aq), 20:5:1 v/v). n_max/cm^-13296br (NH), 3049m,

= 4.3 Hz, 1H, H3(Q)), 7.84 (d, J = 9.0 Hz, 1H, H8(Q)), 7.88 (d, J = 8.3 2938m, 2822m, 1658m, 1623s, 1574m, 1516s, 1466m, 1381s,

Hz, 1H, H4(Q)), 8.58 (d, J = 4.3, 1H, H2(Q)). ¹³C NMR (100.6 MHz, 1323m, 1294m, 1268m, 1244m, 1180m, 1150m, 1124m, 1026s,

CDCl₃): δ = 41.4 (1C, CH₂NH₂), 43.3 (1C, CH₂NQ), 48.0 (1C, 934m, 830s, 789m, 768m, 732m, 699m, 648m, 624m, 548m, 474m,

1

CH₂CH₂NQ), 51.7 (1C, CH₂CH₂NH₂), 102.7 (1C, C7(Q)), 121.2 (1C, 404m, 375m. H NMR (400 MHz, CDCl₃): δ = 2.59 (t, J = 5.7 Hz, 4H,

CH(Q)), 121.5 (1C, CH(Q)), 129.9 (1C, CH(Q)), 130.0 (1C, C4a(Q)), CH₂N), 2.70–2.80 (m, 10H, CH₂N, NH₂), 3.22 (t, J = 5.7 Hz, 2H,

133.6 (1C, CH(Q)), 143.0 (1C, C6(Q)), 145.8 (1C, C2(Q)), 146.2 (1C, CH₂NQ), 5.30 (br. s, 1H, NHQ), 6.65 (d, ⁴J = 2.4 Hz, 1H, H5(Q)), 7.16

C8a(Q)). HRMS (MALDI-TOF): m/z calc. for C₁₃H₁₉N₄: 231.1610; (dd, 1H,J = 9.1 Hz, ⁴J = 2.4 Hz, 1H, H7(Q)), 7.22 (dd, J = 8.3 Hz, J = 4.3

found: 231.1562 [M+H]⁺.

Hz, 1H, H3(Q)), 7.82 (d, J = 9.1 Hz, 1H, H8(Q)), 7.87 (d, J = 8.3 Hz, 1H,

4

H4(Q)), 8.58 (dd, J = 4.3, J = 1.5 Hz, 1H, H2(Q)). ¹³C NMR (100.6

N-(2-{[2-(quinolin-6-ylamino)ethyl]aminoethyl)ethane-1,2-

MHz, CDCl₃): δ = 39.6 (2C, CH₂NH₂), 41.6 (1C, CH₂NQ), 53.0 (1C,

CH₂N), 56.7 (2C, CH₂N), 102.7 (1C, C7(Q)), 121.3 (1C, CH(Q)), 121.6

(1C, CH(Q)), 130.1 (1C, CH(Q)), 130.2 (1C, C4a(Q)), 133.6 (1C,

CH(Q)), 143.1 (1C, C6(Q)), 145.3 (1C. C2(Q)), 146.6 (1C, C8a(Q)).

HRMS (MALDI-TOF): m/z calc. for C₁₅H₂₄N₅: 274.2032; found:

274.1988 [M+H]⁺..

diamine (9c). Compound 9c was obtained from 6-bromoquinoline

(104 mg, 0.5 mmol) and 8c (220 mg, 1.5 mmol) in the presence of

Pd(dba)₂(12 mg, 4 mol%) and BINAP (14 mg, 4.5 mol%). Yield: 54

mg (40%); yellowish oil; chromatography (silica gel,

CH₂Cl₂/MeOH/NH₃(aq), 20:5:1 v/v). n_max/cm^-13311br (NH), 2938m,

2825m, 1658s, 1624s, 1578m, 1509m, 1439m, 1382m, 1246m,

1180m, 1151m, 1125m, 1023s, 831s, 792m, 768m, 624m, 543m, N-(1,4,7,10-tetraazacyclotridecan-5-ylmethyl)quinolin-6-amine

475m. ¹H NMR (400 MHz, CDCl₃): δ = 2.21 (br. s, 4H, NH, NH₂), 2.67 (9f). Compound 9f was obtained from 6-bromoquinoline (104 mg,

3

(t, J = 5.7 Hz, 2H, CH₂N), 2.78 (br. s, 4H, CH₂N), 2.80 (t, J = 5.7 Hz, 0.5 mmol) and 8f (108 mg, 0.5 mmol) in the presence of Pd(dba)₂

2H, CH₂N), 2.95 (t, J = 5.7 Hz, 2H, CH₂N), 3.30 (t, J = 5.7 Hz, 2H, (24 mg, 8 mol%) and BINAP (28 mg, 9 mol%). Yield: 63 mg (37%);

4

CH₂N), 4.72 (br. s, 1H, NHQ), 6.68 (d, J = 2.5 Hz, 1H, H5(Q)), 7.13 yellowish oil; chromatography (silica gel, CH₂Cl₂/MeOH/NH₃(aq),

(dd, 1H, J = 9.1 Hz, ⁴J = 2.5 Hz, 1H, H7(Q)), 7.23 (dd, J = 8.2 Hz, J = 4.2 20:5:1 v/v). n_max/cm^-13279br (NH), 2932m, 2819m, 1659m, 1622s,

Hz, 1H, H3(Q)), 7.83 (d, J = 9.1 Hz, 1H, H8(Q)), 7.88 (d, J = 8.2 Hz, 1H, 1592m, 1576m, 1537m, 1510m, 1493m, 1464m, 1436m, 1380m,

4

H4(Q)), 8.58 (dd, J = 4.2, J = 1.3 Hz, 1H, H2(Q)). ¹³C NMR (100.6 1327m, 1288m, 1269m, 1180m, 1123m, 1029s, 931m, 830s, 767m,

MHz, CDCl₃): δ = 41.4 (1C, CH₂NH), 43.2 (1C, CH₂NQ), 48.1 (1C, 730m, 699m, 646m, 620m, 591m, 545m, 474m. ¹H NMR (400 MHz,

CH₂N), 48.9 (2C, CH₂N), 51.8 (1C, CH₂CH₂NH₂), 102.8 (1C, C7(Q)), CDCl₃): δ = 1.65–1.76 (m, 2H, CH₂CH₂CH₂), 2.55–2.90 (m, 18H,

121.3 (1C, CH(Q)), 121.6 (1C, CH(Q)), 130.1 (2C, CH(Q), C4a(Q)), CH₂N), 2.90–2.98 (m, 1H, CHN), 3.20–3.30 (m, 2H, CH₂NQ), 4.72 (br.

133.7 (1C, CH(Q)), 143.2 (1C, C6(Q)), 146.0 (1C, C2(Q)), 146.4 (1C, s, 1H, NHQ), 6.67 (d, ⁴J = 2.6 Hz, 1H, H5(Q)), 7.13 (dd, 1H, J = 9.1 Hz,

C8a(Q)). HRMS (MALDI-TOF): m/z calc. for C₁₅H₂₄N₅: 274.2032; ⁴J = 2.6 Hz, 1H, H7(Q)), 7.24 (dd, J = 8.3 Hz, ³J = 4.3 Hz, 1H, H3(Q)),

found: 274.2058 [M+H]⁺.

7.83 (d, J = 9.1 Hz, 1H, H8(Q)), 7.89 (d, J = 8.3 Hz, 1H, H4(Q)), 8.59

(dd, J = 4.3, ⁴J = 1.5 Hz, 1H, H2(Q)). ¹³C NMR (100.6 MHz, CDCl₃): δ =

28.4 (1C, CH₂CH₂CH₂), 45.3 (1C, CH₂N), 45.7 (1C, CH₂N), 47.3 (1C,

CH₂N), 48.5 (1C, CH₂N), 48.9 (1C, CH₂N), 49.4 (1C, CH₂N), 49.7 (1C,

CH₂N), 51.0 (1C, CH₂N), 55.8 (1C, CHN), 102.6 (1C, C7(Q)), 121.2 (1C,

CH(Q)), 121.6 (1C, CH(Q)), 130.0 (1C, CH(Q)), 130.1 (1C, C4a(Q)),

133.6 (1C, CH(Q)), 143.0 (1C, C6(Q)), 145.8 (1C, C2(Q)), 146.6 (1C,

C8a(Q)). HRMS (MALDI-TOF): m/ z calc. for C₁₉H₃₁N₆: 343.26; found:

343.28 [M+H]⁺.

N-[3-(quinolin-6-ylamino)propyl]propane-1,3-diamine

(9d).

Compound 9d was obtained from 6-bromoquinoline (104 mg, 0.5

mmol) and 8d (197 mg, 1.5 mmol) in the presence of Pd(dba)₂(12

mg, 4 mol%) and BINAP (14 mg, 4.5 mol%). Yield: 58 mg (45%);

yellowish oil; chromatography (silica gel, CH₂Cl₂/MeOH/NH₃(aq),

100:20:1 v/v). n_max/cm^-13292br (NH), 2936m, 2823m, 1623m,

1531m, 1468m, 1438m, 1381m, 1323m, 1245m, 1179m, 1123m,

1025s, 931m, 829s, 767m, 622m, 747m. ¹H NMR (400 MHz, CDCl₃):

δ = 1.67 (quint, J = 6.9 Hz, 2H, CH₂CH₂CH₂), 1.86 (quint, J = 6.5 Hz,

J. Name., 2013, 00, 1-3 | 13

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Organic & Biomolecular Chemistry

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ARTICLE

Compound 5. A flask equipped with a magnetic stirrer and

Journal Name

189.9 (3C, C(O)). ³¹P{¹H} NMR (162.5 MHz, CDCl₃): δ = 23.5 (2P),

View Article Online

DOI: 10.1039/C9OB00259F

condenser was charged with 9a (65 mg, 0.35 mmol), [(2- 23.6 (1P). HRMS (MALDI TOF): m/z calc. for C₃₄H₆₁N₇O₁₂P₃:

bromoacetylamino)methyl]phosphonic acid diethyl ester 1 (221 mg, 852.3591; found: 852.3539 [M+H]⁺.

0.77 mmol) and chloroform (8.5 ml). DIPEA (150 mg, 1.16 mmol)

was added, and the mixture was stirred at 40°С for 48 h under

argon; the solution was evaporated under vacuum and the residue

was chromatographed (silica gel, CH₂Cl₂, then CH₂Cl₂/MeOH, 200:1

N,N-bis(pyridin-2-ylmethyl)-N'-quinolin-6-ylethane-1,2-diamine

(10). A flask equipped with a magnetic stirrer and condenser was

charged with 9a (65 mg, 0.35 mmol), 2-(chloromethyl)pyridine

hydrochloride (138 mg, 0.84 mmol), potassium iodide (4 mg, 0.02

to 3:1 v/v). Yield: 105 mg (50%); yellowish oil; chromatography

mmol) and acetonitrile (2 mL). DIPEA (220 mg, 1.7 mmol) was

(silica gel, CH₂Cl₂-MeOH, 10:1 v/v). n_max/cm^-13269br (NH), 3048br,

added, and the mixture was stirred under reflux for 12 h under

argon, and then cooled down to r.t.; 30 ml of CH₂Cl₂was added, the

2927br, 2849br, 1663m (C=O,amide I), 1604s, 1588s, 1543m (NH,

amide II), 1508m, 1475m, 1423m, 1409m, 1376m, 1340m,

solution was washed with water (2 ×20 ml), the organic layer was

1301m(CN, amide III), 1272m, 1251m (P=O), 1202m, 1173w, 1139w,

dried over Na₂SO₄, evaporated under vacuum, and the residue was

1114w, 1102w, 1034m (POC), 977m (POC), 860m, 830m, 814m,

chromatographed (silica gel, CH₂Cl₂, then CH₂Cl₂/MeOH, 200:1 to

730m, 701m. ¹H NMR (400 MHz, CDCl₃): δ = 1.25 (t, J = 6.8 Hz, 12H,

3:1 v/v). Yield: 49 mg (38%); yellow oil; chromatography (silica gel,

CH₂Cl₂-MeOH, 35:1 v/v). n_max/cm^-13330br (N-H), 3290w, 3052w,

CH₃), 2.85–2.88 (m, 2H, CH₂N), 3.25 (br. s, 6H, CH₂NQ, CH₂C(O)),

3.54 (dd, ²J_PH= 11.5 Hz, J = 6.2 Hz, 4H, CH₂P(O)), 4.03 (dq, ³J_PH= ³J_HH

3009w, 2923w, 2848w, 1671m, 1623m, 1589m, 1569m, 1510m,

= 6.8 Hz, 8H, CH₂OP), 5.79 (br. s., 1H, NHQ), 6.62 (d, ⁴J = 2.4 Hz, 1H,

1472m, 1433m, 1379m, 1265m, 1246m, 1179m, 1148m, 1122,

1032m, 994m, 931m, 829m, 763m, 633m, 473m, 404s. ¹H NMR

H5(Q)), 7.20 (dd, 1H, J = 4.3 Hz, J = 8.2 Hz, 1H, H3(Q)), 7.36 (dd, J =

4

9.1 Hz, J = 2.4 Hz, 1H, H7(Q)), 7.80 (d, J = 9.1 Hz, 1H, H8(Q)), 7.84

(400 MHz, CDCl₃): δ = 2.94 (t, J = 5.5 Hz, 2H, CH₂N), 3.24 (t, J = 5.5

Hz, 2H, CH₂NQ), 3.91 (s, 4H, CH₂Py), 6.56 (d, ⁴J = 2.5 Hz, 1H, H5(Q)),

(d, J = 8.2 Hz, 1H, H4(Q)), 8.05 (br. m, 2H, NHC(O)), 8.59 (dd, J = 4.3,

3

1H, H2(Q)). ¹³C NMR (100.6 MHz, CDCl₃): δ = 16.4 (d, J_PC= 6.0 Hz,

7.10–7.16 (m, 3H, H7(Q), H5(Py)), 7.23 (dd, J = 8.3 Hz, J = 4.3 Hz, 1H,

1

H3(Q)), 7.39 (d, J = 9.0 Hz, 1H, H3(Py)), 7.59 (td, J = 7.5 Hz, ⁴J = 1.5

4C, CH₃), 34.4 (d, J_PC= 155.9 Hz, 2C, CH₂P(O)), 41.3 (1C, CH₂NQ),

2

54.7 (1C, CH₂N), 59.4 (2C, CH₂C(O)), 62.6 (d, J_PC= 6.4 Hz, 4C,

Hz, 1H, H4(Py))), 7.84–7.86 (m, 2H, H8(Q), H4(Q)), 8.56 (m, 3H,

H2(Q), H6(Py)) (NH proton was not unambiguously assigned). ¹³C

CH₂OP), 102.4 (1C, C7(Q)), 121.2 (1C, CH(Q)), 122.1 (1C, CH(Q)),

129.8 (1C, CH(Q)), 129.9 (1C, C4a(Q)), 133.7 (1C, CH(Q)), 142.9 (1C,

NMR (100.6 MHz, CDCl₃): δ = 41.3 (1C, CH₂N), 52.3 (1C, CH₂NQ),

60.2 (2C, CH₂Py), 102.4 (1C, C7(Q)), 121.2 (1C, CH(Q)), 121.8 (1C,

CH(Q)), 122.2 (2C, CH(Py)), 123.2 (2C, CH(Py)), 129.8 (1C, CH(Q)),

130.2 (1C, C4a(Q)), 133.7 (1C, CH(Q)), 136.5 (2C, CH(Py)), 142.8 (1C,

C6(Q)), 145.8 (1C, C2(Q)), 146.4 (1C, C8a(Q)), 170.1 (1C, C(O)).

³¹P{¹H} NMR (162.5 MHz, CDCl₃): δ = 23.8 (2P). HRMS (MALDI TOF):

m/z calc. for C₂₅H₄₂N₅O₈P₂: 602.2507; found: 602.2515 [M+H]⁺.

Compound 6. A flask equipped with a magnetic stirrer and

C6(Q)), 145.8 (1C, C2(Q)), 146.6 (1C, C8a(Q)), 149.1 (2C, C6(Py)),

condenser was charged with 9b (51 mg, 0.22 mmol), [(2- 159.0 (2C, C2(Py)). HRMS (MALDI TOF): m/z calc. for C₂₃H₂₄N₅

bromoacetylamino)methyl]phosphonic acid diethyl ester 1 (209 mg, 370.2032; found: 370.1990 [M+H]⁺.

0.73 mmol) and chloroform (6.7 ml). DIPEA (128 mg, 0.99 mmol)

Spectroscopic measurements

was added, and the mixture was stirred at at 40°С for 48 h under

All the solutions were prepared with double-deionized high-

argon; the solution was evaporated under vacuum and the residue

purity water (18.2 MΩ cm) obtained from a «Millipore Simplicity»

was chromatographed (silica gel, CH₂Cl₂, then CH₂Cl₂/MeOH, 200:1

apparatus. All metal salts used were perchlorates of general

to 3:1 v/v). Yield: 79 mg (42%); yellowish oil; chromatography (silica

gel, CH₂Cl₂/MeOH, 10:1 v/v). n_max/cm^-13305br (NH), 3056vw ,

M(ClO₄)_n·xH₂O formula. CAUTION! Although no problems were

experienced, perchlorate salts are potentially explosive when

2981w, 2929w, 2906w, 2831vw, 1669m (C=O, amid I), 1653m,

combined with organic ligands and should be manipulated with

1623m, 1576w, 1533m (NH, amide II), 1521m, 1506m, 1456w,

care and used only in very small quantities. The 10^–2-10^–3

M

1436w, 1387m, 1381m, 1368w, 1300w (CN, amideIII), 1219m (P=O),

1161m, 1123m, 1097m, 1045m, 1019s (POC), 972s (POC), 829m,

aqueous solutions of all perchlorates except Hg(ClO₄)₂were

prepared in order to prevent the influence of dilution on the

recorded spectra. Hg(ClO₄)₂was used as a 10^–2M solution in

acetonitrile to avoid the hydrolysis of the salt. 0.03 M HEPES buffer

(pH = 7.4) was prepared in beaker by the addition of 10 M NaOH

solution by droplets to 0.03 M standard solution of HEPES under pH

control until pH achieved 7.4.

1

804m, 768m, 731m, 679m, 668s, 649m, 617m. H NMR (400 MHz,

CDCl₃): δ = 1.30 (t, J = 6.8 Hz, 12H, CH₃), 1.31 (t, J = 6.8 Hz, 6H, CH₃),

2.72–2.81 (m, 6H, CH₂N), 3.13 (br. s., 6H, CH₂C(O)), 3.22–3.24 (m,

2H, CH₂NQ), 3.70–3.84 (m, 6H, CH₂P(O)), 4.07–4.18 (m, 12H,

4

CH₂OP), 5.69 (br. s, 1H, NHQ), 6.63 (d, J = 2.5 Hz, 1H, H5(Q)), 7.28

(dd, 1H, J = 4.3 Hz, J = 8.4 Hz, 1H, H3(Q)), 7.49 (dd, J = 9.1 Hz, ⁴J = 2.5

Hz, 1H, H7(Q)), 7.86 (d, J = 9.1 Hz, 1H, H8(Q)), 7.85 (d, J = 8.4 Hz, 1H,

H4(Q)), 8.54–8.59 (m, 4H, H2(Q), NHC(O)). ¹³C NMR (100.6 MHz,

Spectrophotometric titrations

Determination of protonation constants. pH measurements

3

1

CDCl₃): δ = 16.4 (d, J_PC= 6.0 Hz, 6C, CH₃), 34.2 (d, J_PC= 156.0 Hz, were carried out using «Mettler Toledo» apparatus with combined

1

1C, CH₂P(O)), 34.5 (d, J_PC= 156.0 Hz, 2C, CH₂P(O)), 40.6 (1C, electrode LE438. The electrode was calibrated with commercial

CH₂NQ), 52.1 (1C, CH₂N), 53.2 (1C, CH₂N), 54.2 (1C, CH₂N), 57.1 (1C, buffers (pH = 4.01 and 7.00). Protonation studies were conducted in

CH₂C(O)), 58.5 (2C, CH₂C(O)), 62.6 (d, ²J_PC= 6.6 Hz, 4C, CH₂OP), 62.8 a glass beaker, equipped with magnetic stirrer and pH-electrode.

2

(d, J_PC= 6.6 Hz, 2C, CH₂OP), 102.1 (1C, C7(Q)), 121.3 (1C, CH(Q)), Aliquots of acid or base were added manually through LLG-digital

122.8 (1C, CH(Q)), 128.7 (1C, CH(Q)), 130.4 (1C, C4a(Q)), 134.6 (1C, micropipette to polyamines 5, 6 and 10 solutions of appropriate

CH(Q)), 140.3 (1C, С8a(Q)), 144.7 (1C, C6(Q)), 147.1 (1C, C2(Q)), concentrations and containing potassium chloride (KCl, C = 0.1 M).

14 | J. Name., 2012, 00, 1-3

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Organic & Biomolecular Chemistry

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Journal Name

ARTICLE

Experimental details for each experiment are detailed in the at aliphatic amino groups is the key parameter for tuning solubility

View Article Online

DOI: 10.1039/C9OB00259F

captions for the figures. The entire multiwavelength data sets and sensing properties of 6-polyaminoquinolines with respect to

comprising at least 20 spectra were decomposed into their principal toxic metal ions. Chelator 10 bearing 2-pinacolyl residues is

components by factor analysis before adjusting the equilibrium insoluble in pure water and produces optical response for many

constants and calculations of extinction coefficients or normalized metal ions in aqueous media. In contrast, chemosensor 5 containing

fluorescence spectra by nonlinear least-squares analysis with the carboxyamide moieties are suitable for selective double-channel

Specfit/32 program.^38,52

detection of Cu^IIions under biologically and environmentally

Determination of stability constants of complexes. Aliquots of relevant conditions (aqueous media at pH = 7.4). This compound

metal salts were added manually with the help of a Hamilton demonstrates low LOD of cupric ions and is suitable for the analysis

syringe to solutions of the chelators 5 and 6 of appropriate of drinking water.

concentrations. Experimental details for each experiment are

Increasing the number of donor sites in the polyamine

detailed in the captions of the figures. The spectra were recorded at ionophore, the selectivity of amidophosphonate-substituted 6-

pH = 7.4 (0.03 M HEPES buffer). The entire multiwavelength data polyaminoquinolines towards toxic metal ions can be turned.

sets comprising at least 20 spectra were decomposed into their Chemosensor 6 is useful for a sensitive detection of Hg^IIions under

principal components by factor analysis before adjusting the physiological conditions. Among 15 different metal ions, only Cu^II

equilibrium constants and calculations of extinction coefficients or ions strongly disturbs the analysis of mercury(II) cations. Moreover,

normalized fluorescence spectra by nonlinear least-squares analysis chemosensor 6 is a rare receptor able to produce three different

with the Specfit/32 program.^38,52The calculation of stability fluorescence responses on the presence of Hg^II, Cu^IIand Zn^IIions in

constant were performed taken into account the stability constants aqueous solution. Such chemosensors are of particular interest for

for the hydrolysed metal ion species.

a complex analysis of industrial wastes and environmental samples

coming from contaminated regions.

Preparation of test-strips

The stripes were performed from filtrate paper (GOST 12026-76,

Russia) in size 10 x 50 mm. The stripe was dipped into the test-tube

with the solution of the ligand (C = 1.3 mM) for 1 min, that dried on

air. The droplets of different solutions were placed on the stripe,

than the stripe was shown under UV-light lamp (365 nm).

Conflicts of interest

The authors declare no conflicts of interest.

Acknowledgements

Conclusions

This work was carried out in the frames of the International

Associated French-Russian Laboratory of Macrocyclic systems and

Related Materials (LIA LAMREM) of the Centre National de la

Recherche Scientifique (CNRS) and the Russian Academy of Sciences

(RAS). We thank the CNRS, Russian Foundation for Basic Researches

(RFBR) (grant N 17-53-16012), the Conseil Régional de Bourgogne

(program PARI II) for financial support. The authors thank Dr.

Michel Mayer for helpful discussions on FT–IR data. The authors

thank Dr. Yury K. Grishin for providing structural NMR studies. The

authors wish to acknowledge Thermo Fisher Scientific, Inc., MS

Analytica (Moscow, Russia), and Prof. A. Makarov (Thermo Fisher

Scientific, Inc.) personally for providing mass spectrometry

equipment for this work. The authors wish to acknowledge the use

of the NMR equipment purchased within the M.V. Lomonosov

Moscow State University Program of Development.

A

convenient synthetic approach to polyamines bearing

chromogenic quinolin-6-yl residue has been developed. Being

conducted in the presence of a relatively cheap and commercially

available palladium precatalyst, chemoselective arylation of non-

protected

polyamines

with

6-bromoquinoline

afforded

monoarylated derivatives when the reaction was performed with

polyamines taken in excess. In contrast to previously reported

copper-catalyzed heterocoupling of 6-bromoquinoline with

polyamines, the scope of this chemoselective reaction is quite large

and target products can be obtained in good yields (up to 75%).

Polyamines bearing quinolin-6-yl residue are of interest for

development of chemosensors for environmental analysis and

clinical diagnostics. The protonation or coordination of metal ions

by such chelators may induce large changes of their absorptive and

emissive properties because the signaling aromatic unit is directly

attached to the polyamine ionophore. In addition, further N-

functionalization of the polyamine unit can be used to turn

solubility and sensing properties of 6-polyaminoquinolines with

respect to toxic metal ions. This synthetic route is convenient for

the preparation of small libraries of molecular probes in which both

the polyamine unit and the additional donor sites in the

substituents at the nitrogen atoms can be varied. Proof of this

concept is the synthesis of novel chemosensors for selective

detection of Cu^IIand Hg^IIions under physiological conditions.

Notes and references

All obtained compounds 5, 6 and 10 act as pH sensitive sensors

responsing to pH changes by the evolution of absorption and

emission of their solutions. However, the nature of the substituent

J. Name., 2013, 00, 1-3 | 15

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Organic & Biomolecular Chemistry

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ARTICLE

Journal Name

1 (a) Fluorescent Chemosensors for Ion and Molecule 15 (a) G. Pourfallah and X. Lou, Dyes Pigm., 2018, _V1_i5_ew8,_Ar1_ti2_cl;_e(_Ob_n)_linB_e.

Recognition, Vol. 538, American Chemical Society,

Washington, DC, 1993, pp.1-235; (b) A. W. Czarnik, Chem.

Biol., 1995, 2, 423; (c) A. P. de Silva, H. Q. N. Gunaratne, T.

K. Datta, S. Mukherjee, C. Kar, A. Ra^Dm^Oe^Is^:h¹⁰a^.1n⁰d³⁹G^/C. ⁹D^Oa^Bs⁰, ⁰A²n⁵a^9Fl.

Chem., 2013, 85, 8369; (c) Z. Dong, Y. Guo, X. Tian and J. Ma,

J. Lumin., 2013, 134, 635.

Gunnlaugsson, A. J. M. Huxley, C. P. McCoy, J. T. Rademacher 16 J.-F. Zhu, H. Yuan, W.-H. Chan and A. W. M. Lee, Tetrahedron

and T. E. Rice, Chem. Rev., 1997, 97, 1515-1566; (d) B. Valeur Lett., 2010, 51, 3550.

and I. Leray, Coord. Chem. Rev., 2000, 205, 3; (e) M. Formica, 17 W.-J. Qu, J. Guan, T.-B. Wei, G.-T. Yan, Q. Lin and Y.-M. Zhang,

V. Fusi, L. Giorgi and M. Micheloni, Coord. Chem. Rev., 2012,

256, 170.

RSC Adv., 2016, 6, 35804.

18 S. Patra, R. Gunupuru, R. Lo, E. Suresh, B. Ganguly and P. Paul,

2

(a) L. A. Bakar, N. M. Amin and H. A. Zakeri, Procedia Environ.

New J. Chem., 2012, 36, 988.

Sci., 2015, 30, 222-227; (b) J. K. Schaefer, A. Szczuka and F. M. 19 (a) A. Pramanik and G. Das, Tetrahedron, 2009, 65, 2196; (b)

M. Morel, Environ. Sci. Technol., 2014, 48, 3007.

K. G. Vaswani and M. D. Keränen, Inorg. Chem., 2009, 48,

5797; (c) Z. Dong, J. Jin, W. Zhao, H. Geng, P. Zhao, R. Li and J.

Ma, Appl. Surf. Sci., 2009, 255, 9526; (d) J. Kang, S. P. Jang, Y.-

H. Kim, J. H. Lee, E. B. Park, H. G. Lee, J. H. Kim, Y. Kim, S.-J.

Kim and C. Kim, Tetrahedron Lett., 2010, 51, 6658; (e) L. Tang,

P. Zhou, Z. Huang, J. Zhao and M. Cai, Tetrahedron Lett., 2013,

54, 5948; (f) X. Jia, X. Yu, X. Yang, J. Cui, X. Tang, W. Liu and W.

Qin, Dyes Pigm., 2013, 98, 195; (g) L. Zhang, J. Sun, S. Liu, X.

Cui, W. Li and J. Fang, Inorg. Chem. Commun., 2013, 35, 311;

(h) P. Khakhlary and J. B. Baruah, Inorg. Chim. Acta, 2016, 440,

53; (i) L. Wang, J. Jin, L. Zhao, H. Shen, C. Shen and P. Zhang,

Carbohydr. Res., 2016, 433, 41; (J) S. Zeng, S.-J. Li, X.-J. Sun,

M.-Q. Li, Y.-Q. Ma, Z.-Y. Xing and J.-L. Li, Spectrochim. Acta A,

2018, 205, 276.

3

4

5

http://www.

epa.gov/mercury/exposure.htm

(accessed

Februry 2019).

C. J. Frederickson, J.-Y. Koh and A. I. Bush, Nat. Rev. Neurosci.,

2005, 6, 449.

S. L. Sensi, P. Paoletti, A. I. Bush and I. Sekler, Nat. Rev.

Neurosci., 2009, 10, 780.

V. Desai and S. G. Kaler, Am. J. Clin. Nutr., 2008, 88, 855S.

https://www.epa.gov/eg/battery-manufacturing-effluent-

guidelines-documents (accessed Februry 2019).

M. A. Haque, V. Subramanian and R. J. Gibbs, Crit. Rev.

Environ. Control, 1982, 12, 13.

6

7

8

9

(a) P. Jiang and Z. Guo, Coord. Chem. Rev., 2004, 248, 205; (b)

D. P. Selid, H. Xu, E. M. Collins, M. Striped Face-Collins and J.

X. Zhao, Sensors, 2009, 9, 5446; (c) D. T. Quang and J. S. Kim, 20 (a) E. M. Nolan, J. Jaworski, K.-I. Okamoto, Y. Hayashi, M.

Chem. Rev., 2010, 110, 6280; (d) I. Ratera, A. Tárraga, P.

Molina and J. Veciana, in Organic Nanomaterials: Synthesis,

Characterization,nd Device Applications, eds. T. Torres and G.

Bottari, 2013, Chap. 24, p. 529-548; (e) X. Qian and Z. Xu,

Chem. Soc. Rev., 2015, 44, 4487; (f) G . Chen, Z. Guo, G. Zeng

and L. Tang, Analyst, 2015, 140, 5400; (g) G. Sivaraman, M.

Iniya, T. Anand, N. G. Kotla, O. Sunnapu, S. Singaravadivel, A.

Gulyani and D. Chellappa, Coord. Chem. Rev., 2018, 357, 50;

(h) S. Suganya, S. Naha and S. Velmathi, ChemistrySelect,

2018, 3, 7231.

Sheng and S. J. Lippard, J. Am. Chem. Soc., 2005, 127, 16812;

(b) Y. Zhang, X. Guo, W. Si, L. Jia and X. Qian, Org. Lett., 2008,

10, 473; (c) N. Zhang, Y. Chen, M. Yu and Y. Liu, Chem. – Asian

J., 2009, 4, 1697; (d) X. Zhou, B. Yu, Y. Guo, X. Tang, H. Zhang

and W. Liu, Inorg. Chem., 2010, 49, 4002; (e) G. Xie, P. Xi, X.

Wang, X. Zhao, L. Huang, F. Chen, Y. Wu, X. Yao and Z. Zeng,

Eur. J. Inorg. Chem., 2011, 2011, 2927; (f) T. Liu and S. Liu,

Anal. Chem., 2011, 83, 2775.; (g) X. Tian, X. Guo, L. Jia, R.

Yang, G. Cao and C. Liu, Sens. Actuators B-Chem., 2015, 221,

923; (h) X. Zhou, Y. Lu, J.-F. Zhu, W.-H. Chan, A. W. M. Lee, P.-

S. Chan, R. N. S. Wong and N. K. Mak, Tetrahedron, 2011, 67,

3412; (i) M.-h. Yan, T.-r. Li and Z.-y. Yang, Inorg. Chem.

Commun., 2011, 14, 463; (j) Y. Ma, F. Wang, S. Kambam and X.

Chen, Sens. Actuators B-Chem., 2013, 188, 1116.

10 (a) B. Nisar Ahamed, I. Ravikumar and P. Ghosh, New J. Chem.,

2009, 33, 1825; (b) M. Alfonso, A. Tárraga and P. Molina, J.

Org. Chem., 2011, 76, 939; (c) J.-W. Oh, T. H. Kim, S. W. Yoo, Y.

O. Lee, Y. Lee, H. Kim, J. Kim and J. S. Kim, Sens. Actuators B-

Chem., 2013, 177, 813; (d) S. Madhu, D. K. Sharma, S. K. Basu, 21 (a) Y. Wan, W. Niu, W. J. Behof, Y. Wang, P. Boyle and C. B.

S. Jadhav, A. Chowdhury and M. Ravikanth, Inorg. Chem.,

2013, 52, 11136; (e) T. Zhang, G. She, X. Qi and L. Mu,

Gorman, Tetrahedron, 2009, 65, 4293-4297; (b) P. Kaur, H.

Kaur and K. Singh, RSC Adv., 2013, 3, 64.

Tetrahedron, 2013, 69, 7102; (f) P. Molina, A. Tárraga and M. 22 (a) S. G. Schulman, K. Abate, P. J. Kovi, A. C. Capomacchia and

Alfonso, Dalton Trans., 2014, 43, 18; (g) Y. Liu, Q. Teng, J. Hu,

R. Sun and H. Zhang, Sens. Actuators B-Chem., 2016, 234, 680-

690; (h) Y. Fang, Y. Zhou, Q. Rui and C. Yao, Organometallics,

2015, 34, 2962; (i) A. Hazra, A. Roy, A. Mukherjee, G. P. Maiti

and P. Roy, Dalton Trans., 2018, 47, 13972.

D. Jackman, Anal. Chim. Acta, 1973, 65, 59; (b) A. Rajapakse,

C. Linder, R. D. Morrison, U. Sarkar, N. D. Leigh, C. L. Barnes, J.

S. Daniels and K. S. Gates, Chem. Res. Toxicol., 2013, 26, 555;

(c) Y.-C. Cai, C. Li and Q.-H. Song, ACS Sensors, 2017, 2, 834.

23 (a) W. Nashabeh and Z. El Rassi, J. Chromatogr. A, 1992, 600,

279; (b) Y. Mechref, G. K. Ostrander and Z. El Rassi, J.

Chromatogr. A, 1995, 695, 83; (c) J. J. Wilson and J. S.

Brodbelt, Anal. Chem., 2008, 80, 5186; (d) W. B. Struwe and P.

M. Rudd, Biol. Chem., 2012, 393, 757.

11 T. Michinobu, Y. Li and T. Hyakutake, Phys. Chem. Chem.

Phys., 2013, 15, 2623.

12 (a) E. Ranyuk, C. M. Douaihy, A. Bessmertnykh, F. Denat, A.

Averin, I. Beletskaya and R. Guilard, Org. Lett., 2009, 11, 987;

(b) A. S. Abel, A. Y. Mitrofanov, Y. Rousselin, F. Denat, A. 24 M. Jonnada, G. D. El Rassi and Z. El Rassi, Electrophoresis,

Bessmertnykh-Lemeune, A. D. Averin and I. P. Beletskaya,

ChemPlusChem, 2015, 81, 35.

2017, 38, 1592.

25 F. Tanaka, R. Thayumanavan and C. F. Barbas, J. Am. Chem.

13 C. Hu, V. Raja Solomon, P. Cano and H. Lee, Eur. J. Med.

Chem., 2010, 45, 705.

14 (a) R. Cheng, Y. Liu, S. Ou, Y. Pan, S. Zhang, H. Chen, L. Dai and

J. Qu, Anal. Chem., 2012, 84, 5641; (b) S. K. Rastogi, P. Pal, D.

E. Aston, T. E. Bitterwolf and A. L. Branen, ACS Appl. Mat.

Interfaces, 2011, 3, 1731.

Soc., 2003, 125, 8523.

26 (a) P. J. Brynes, P. Bevilacqua and A. Green, Anal. Biochem.,

1981, 116, 408-413; (b) S. A. Cohen and D. P. Michaud, Anal.

Biochem., 1993, 211, 279; (c) W. Huang, S. N. Hicks, J. Sondek

and Q. Zhang, ACS Chem. Biol., 2011, 6, 223; (d) E. Danieli and

D. Shabat, Bioorg. Med. Chem., 2007, 15, 7318.

16 | J. Name., 2012, 00, 1-3

Please do not adjust margins

Page 17 of 17

Organic & Biomolecular Chemistry

Please do not adjust margins

Journal Name

ARTICLE

27 (a) S. Halder, A. Hazra and P. Roy, J. Lumin., 2018, 195, 326;

(b) S. Halder, S. Dey and P. Roy, RSC Adv., 2015, 5, 54873.

28 (a) D. W. Kim, J. Kim, J. Hwang, J. K. Park and J. S. Kim, Bull.

Korean Chem. Soc., 2012, 33, 1159; (b) A. Dorazco-González,

M. F. Alamo, C. Godoy-Alcántar, H. Höpfl and A. K.

Yatsimirsky, RSC Adv., 2014, 4, 455; (c) I. J. Bazany-Rodríguez,

D. Martínez-Otero, J. Barroso-Flores, A. K. Yatsimirsky and A.

Dorazco-González, Sens. Actuators B-Chem., 2015, 221, 1348.

29 L. D. Chebrolu, S. Thurakkal, H. S. Balaraman and R.

Danaboyina, Sens. Actuators B-Chem., 2014, 204, 480.

30 (a) L. Xue, G. Li, Q. Liu, H. Wang, C. Liu, X. Ding, S. He and H.

Jiang, Inorg. Chem., 2011, 50, 3680; (b) Z. Liu, G. Li, Y. Wang, J.

Li, Y. Mi, D. Zou, T. Li and Y. Wu, Talanta, 2019, 192, 6.

31 A. S. Abel, A. D. Averin and I. P. Beletskaya, New J. Chem.,

2016, 40, 5818-5828.

View Article Online

DOI: 10.1039/C9OB00259F

32 J. F. Callan, A. P. de Silva, J. Ferguson, A. J. M. Huxley and A.

M. O'Brien, Tetrahedron, 2004, 60, 11125.

33 M. Mei and S. Wu, New J. Chem., 2001, 25, 471.

34 S. Banthia and A. Samanta, J. Phys. Chem. B, 2006, 110, 6437.

35 I. P. Beletskaya, A. G. Bessmertnykh and R. Guilard,

Tetrahedron Lett., 1997, 38, 2287.

36 I. P. Beletskaya, A. D. Averin, A. G. Bessmertnykh, F. Denat

and R. Guilard, Russ. J. Org. Chem., 2010, 46, 947.

37 M. V. Anokhin, A. D. Averin, S. P. Panchenko, O. A.

Maloshitskaya and I. P. Beletskaya, Mendeleev Commun.,

2015, 25, 245.

38 H. Gampp, M. Maeder, C. J. Meyer and A. D. Zuberbuhler,

Talanta, 1985, 32, 257.

39 E. Ranyuk, A. Uglov, M. Meyer, A. B. Lemeune, F. Denat, A.

Averin, I. Beletskaya and R. Guilard, Dalton Trans., 2011, 40,

10491.

40 B. A. Wong, S. Friedle and S. J. Lippard, Inorg. Chem., 2009,

48, 7009.

41 D. J. Anderson, Clin. Chem., 1989, 35, 2152.

42 Z. Slovák and J. Borák, Anal. Chim. Acta, 1974, 68, 425.

43 P. MacCarthy, Anal. Chem., 1978, 50, 2165.

44 M. Meyer, L. Frémond, E. Espinosa, R. Guilard, Z. Ou and K. M.

Kadish, Inorg. Chem., 2004, 43, 5572.

45 A. A. Granovsky, Firefly version 8, http://classic.chem.msu.su/

gran/firefly/index.html (accessed Februry 2019).

46 M.W.Schmidt,

M.S.Gordon, J.H.Jensen, S.Koseki, N.Matsunaga, K.A.Nguyen,

S.Su, T.L.Windus, M.Dupuis and J.A.Montgomery,

J.Comput.Chem., 1993, 14, 1347.

K.K.Baldridge,

J.A.Boatz,

S.T.Elbert,

47 (a) L. Tang, P. Zhou, Z. Qi, Z. Huang, J. Zhao and M. Cai, Bull.

Korean Chem. Soc., 2013, 34, 2256; (b) L. Tang, P. Zhou, Q.

Zhang, Z. Huang, J. Zhao and M. Cai, Inorg. Chem. Commun.,

2013, 36, 100; (c) C. Gao, X. Liu, X. Jin, J. Wu, Y. Xie, W. Liu, X.

Yao and Y. Tang, Sens. Actuators B-Chem., 2013, 185, 125.

48 F. K. Kálmán, M. Woods, P. Caravan, P. Jurek, M. Spiller, G.

Tircsó, R. Király, E. Brücher and A. D. Sherry, Inorg. Chem.,

2007, 46, 5260.

49 T. Ukai, H. Kawazura, Y. Ishii, J. J. Bonnet and J. A. Ibers, J.

Organomet. Chem., 1974, 65, 253.

50 A. M. Brouwer, Pure Appl. Chem., 2011, 83, 2213.

51 G. B. Behera, P. C. Rath and M. K. Rout, J. Indian Chem. Soc.,

1967, 44, 119.

52 R. A. Binstead, B. Jung and A. D. Zuverbühler, SPECFIT/32,

Global Analysis System, ver 3.0; Spectrum Software

Associates: Marlborough, USA, 2000.

J. Name., 2013, 00, 1-3 | 17

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6-Polyamino-substituted quinolines: Synthesis and multiple metal (CuII, HgII and ZnII) monitoring in aqueous media

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