Synthesis, structures and properties of self-assembling quaternary ammonium dansyl fluorescent tags for porous and non-porous surfaces

Article abstract of DOI:10.1039/c3tb21633k

A series of H₂O and/or EtOH soluble, self-assembling quaternary ammonium salts containing a dansyl (DNS) fluorescent moiety suitable for attachment to both porous ([DNS-NH-(CH₂)₃-NMe ₂-R⁺][X^-

Full text of DOI:10.1039/c3tb21633k

Journal of
Materials Chemistry B
View Article Online
View Journal | View Issue
PAPER
Synthesis, structures and properties of self-
assembling quaternary ammonium dansyl
fluorescent tags for porous and non-porous
surfaces†
Cite this: J. Mater. Chem. B, 2014, 2,
1509
Lukasz M. Porosa,a Kamlesh B. Mistry,a Amanda Mocella,a Hellen Deng,a
Shayan Hamzehi,a Alex Caschera,a Alan J. Lough,b Gideon Wolfaardta
a
*
and Daniel A. Foucher
A series of H2O and/or EtOH soluble, self-assembling quaternary ammonium salts containing a dansyl (DNS)
fluorescent moiety suitable for attachment to both porous ([DNS–NH–(CH2)3–NMe2–R+][Xꢀ] (2; R ¼
–Si(OMe)3, Xꢀ ¼ Clꢀ) and non-porous (3a; R ¼ –PO(OEt)2, 3b; –PO(Oi-Pr)2, 3c; –(PO(OH)2, Xꢀ ¼ Brꢀ), 4;
([DNS–NH–(CH2)3–NMe2–(CH2)3–NH(CH2PO(OEt)2)2+][Brꢀ], 5; R ¼ –((CH2)3SCOCH3, Xꢀ ¼ Clꢀ), 6a; (R
¼ –(CH2)nO(C6H4)CO(C6H5), n ¼ 3, Xꢀ ¼ Brꢀ, 6b; n ¼ 3, Xꢀ ¼ Clꢀ, 6c; n ¼ 3, Xꢀ ¼ Iꢀ, 6d; n ¼ 4, Xꢀ
¼
Brꢀ, 6e; n ¼ 4, Xꢀ ¼ Iꢀ, 6f; n ¼ 6, Xꢀ ¼ Brꢀ, 6g; n ¼ 6, Xꢀ ¼ Clꢀ, 6h; n ¼ 6, Xꢀ ¼ Iꢀ), 7; (R ¼ –CH2–
CH]CH2, Xꢀ ¼ Brꢀ) surfaces were prepared from the precursor dansyl amine (1; DNS–NH–(CH2)3–
NMe2). Compounds 1–7 were characterized by NMR (1H, 13C, 29Si (2), 31P (3a–c, 4)) spectroscopy, HRMS,
UV-Vis and fluorescence spectroscopy. Additional characterization of compounds 1 and 7 were carried
out by X-ray structure determinations. Physical attachment of compound 2 to cotton surfaces after
immersion in solutions containing fluorescent dyes was verified by exposure to UV light and by
complexation with bromo-phenol blue that rendered the surfaces visibly blue in colour. Phosphorus
containing dansyl fluorescent dye, 3c, was attached to a stainless steel surface by exposure to an
aqueous solution containing this dye, resulting in the formation of a self-assembled fluorescent
monolayer. UV cure of plastic surfaces (polypropylene, silicon medical tubing) coated with compound 6a
resulted in the covalent attachment of the dyes.
Received 19th November 2013
Accepted 24th January 2014
DOI: 10.1039/c3tb21633k
www.rsc.org/MaterialsB
of microorganisms with clinical importance (pathogens), there
is either no efficacious therapy or only one or two effective
Introduction
antibiotics that are difficult to administer, expensive and/or
have increasingly toxic side effects. Furthermore, when growing
on surfaces as biolms, microorganisms are generally more
persistent, and it is now estimated that the majority of infec-
tions (65–80%) involve these biolms in some form.4 Biolms
also pose a notable threat of contamination in food processing
facilities and spoilage of other products susceptible to micro-
bial attack.5 One approach in preventing pathogenic biolm
formation, and thus the potential to cause spoilage or infection,
is the use of antimicrobial coatings on surfaces that are not
susceptible to the development of resistance by the target
microorganisms.1,6,7 These coatings have bacteriostatic (inhib-
iting) or bactericidal (killing)8–12 properties and thus afford a
preventative strategy compared to disinfection, which is reac-
tive, oen aer some damage or infection has occurred. In
contrast to conventional antibiotics, bacteria do not readily
develop resistance to antimicrobial coatings that inhibit
microorganisms in a mechanical, as opposed to a chemical,
fashion. This important distinction, and the related alarming
Infection control and reduction of the spread of microorgan-
isms such as fungi and bacteria is a key challenge facing health
care providers. Many microorganisms have the ability to attach
to surfaces and proliferate, forming colonies called biolms.1
The use of antibiotics to treat infectious diseases, including
those caused by biolms, is one of the most signicant medical
developments over the last century. However, aer widespread
use of these antibiotics, as well as other chemicals used for the
purpose of disinfection, several strains of microorganisms (e.g.
bacteria), have developed resistance.2–4 For the growing number
aDepartment of Chemistry and Biology, Ryerson University, 350 Victoria Street,
Toronto, Ontario, Canada M5B-2K3. E-mail: daniel.foucher@ryerson.ca
bDepartment of Chemistry, University of Toronto, 80 St. George Street, Toronto,
Ontario, Canada, M5S 3H6. E-mail: alough@chem.utoronto.ca
† Electronic supplementary information (ESI) available: (a) NMR (1H, 13C, and
where identied, 29Si, 31P NMR data) for all synthesized compounds, (b) DART
or ESI-TOF MS spectra for new compounds, (c) X-ray crystallographic data for
compounds 1 and 7. CCDC 971464 and 971465. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c3tb21633k
This journal is © The Royal Society of Chemistry 2014
J. Mater. Chem. B, 2014, 2, 1509–1520 | 1509

View Article Online
Journal of Materials Chemistry B
Paper
rate at which the number of effective antibiotics has declined, is nitroarenes),32 whereas SAM's on silicon were used to sense pH,
a primary reason for the rapidly growing interest in antimicro- Hg2+, Clꢀ, and Brꢀ ions.33 Other functionalized dansyl probes
bial coatings in recent years.13–20
have been used to study various diseases. In a study of the effect
Quaternary ammonium compounds (“QAC's”) including of copper on Alzheimer's and Wilson's diseases, Pitchumani
benzylalkonium salts (Fig. 1), are well established as surfac- designed dansyl-thiol silver nanoparticles for sensing Cu2+
tants, possess antimicrobial activity and are used as disinfec- ions.31 Meanwhile, Viirre and his group utilized Pd catalysis
tants.21,22 QAC's consist of an irreversibly positively charged chemistry to incorporate a dansyl probe for the study of
quaternary nitrogen atom where at least one substituent is oen protein–protein interactions in cystic brosis research.34 Dansyl
a long aliphatic chain. The synthesis of these compounds phosphonic acid was also recently used to help elucidate orga-
involves the quaternization of a tertiary amine following a nophosphonate metabolism in bacteria.35
Menshutkin reaction (i.e. a reaction of a tertiary amine with an
alkyl halide).23–25 Surface bound antimicrobial QAC surface
coatings, such as dimethyloctadecyl[3-(trimethoxysilyl)propyl]-
ammonium chloride, were rst described by Isquith et al. who
Experiments and methods
Materials
bound dimethyloctadecyl ammonium chloride via a silane The reagents, 3-(dimethylamino)propylamine, 3-(chloropropyl)-
anchor onto a variety of polyhydroxy surfaces.8,26–28 Research trimethoxysilane, diethyl(3-bromopropyl)phosphonate, N,N0-
into developing alternative ways of graing QAC's to a multi- dimethylethylenediamine,
3-chlorpropylthioacetate,
allyl
tude of surfaces is hampered by the lack of simple, rapid and bromide, ACN, EtOH, were used as received (Sigma Aldrich).
non-destructive detection methods for these coatings aer they Anhydrous DCM and Et2O were obtained by passage through a
are applied. Traditionally, detection of surface silane bound bed of activated molecular sieves under an atmosphere of dry
QAC's on textiles has been achieved by visible staining of treated
N2(g). Dansyl chloride (>97%) was used as received (Alfa Aesar).
surfaces with a dilute aqueous solution of the bromophenol All uorescent compounds were stored in glass vials in the
blue dye, 4,40-(1,1-dioxido-3H-2,1-benzoxathiole-3,3-diyl)bis(2,6- absence of light.
dibromophenol).29 Bromophenol blue is a water soluble anionic
Nuclear magnetic resonance (NMR) experiments were
dye that readily binds to QAC's and is characterized by a strong recorded on a 400 MHz Bruker Avance II Spectrometer using
blue coloured ion pair that is visible to the naked eye. However, deuterated chloroform (CDCl3) as the solvent unless otherwise
1
this dye oen irreversibly binds to the textile, visibly staining indicated. H and 13C{1H} NMR spectra were referenced to the
the surface and destroying the material for future use. One residual CHCl3 (dH ¼ 7.26 ppm) and the central peak of CDCl3
solution that we envisioned was the use of surface anchored, (dC ¼ 77.0 ppm) solvent signal respectively. The 31P{1H} spectra
water soluble QAC's functionalized with a uorescent dansyl tag were referenced externally to 85% phosphoric acid (dP ¼ 0.00
as an inexpensive, rapid and simple alternative to bromophenol ppm). Proton chemical shi assignments given in d (ppm) were
blue for the facile detection of product surface coverage and interpreted with the aid of 2-D COSY spectra, while carbon
coating uniformity. Thus, treated surfaces would glow uores- chemical shi assignments given in d (ppm) were interpreted
cent under exposure to a low power UV lamp, identifying areas with the aid of 2-D HSQC spectra. Microwave reactions were
of poor adhesion as well as missed areas during application. performed in sealed glass reaction tubes utilizing the Biotage®
Additionally, it can also act as a unique product identier and Initiator Microwave Synthesizer (2.45 GHz). UV-Vis and uo-
security feature for treated surfaces when added in trace rescence measurements were recorded on a Perkin Elmer
amounts to functional antimicrobial solutions.
Spectrophotometer (Lambda 20) and a Perkin Elmer Lumines-
The dansyl uorophore, capable of intermolecular charge- cence Spectrophotometer (LS 50B) respectively at the Ryerson
transfer, possesses high emission quantum yields and displays University Analytical Centre (RUAC). High resolution mass
solvatochromism in the excited state giving rise to interesting spectra (HRMS) were recorded by direct analysis in real time by
and useful uorescence properties.30,31 Along with the chemical DART-TOF or by electrospray time-of-ight (ESI-TOF) at the
exibility of the sulfonic acid group, the dansyl amide has been Advanced Instrumentation for Molecular Structure (AIMS)
utilized in various applications ranging from chemical sensing laboratory at the University of Toronto. X-ray crystal structure
materials for the detection of explosives, biological weapons, analysis was performed with a Bruker-Nonius Kappa-CCD
metal ions, pH and as a probe/label for amino acids in the study diffractometer at the University of Toronto X-ray diffraction
of various diseases and metabolic pathways. For example, facilities. Thin Layer Chromatography (TLC) was carried out on
dansyl-functionalized organosilane self-assembled monolayers Silica gel 60 aluminium backed plates and visualized with a UV
(SAM's) on glass surfaces were used to sense explosives (e.g. lamp or staining with (KMnO4 or Ninhydrin). Melting points
were measured using a Fischer Scientic melting point appa-
ratus. UV curing of samples was achieved with a Novocure UV
curing system from EFOS. UV curing of samples was initiated by
UV curing at UV(A) (320–390 nm) and UV(V) (395–445 nm)
wavelengths by exposing 1 ꢁ 1 cm2 samples for 2.5 min at
distance of 5 cm from the light source. Samples were subjected
to an average UV dosage of 3.80 ꢂ 0.369 J cmꢀ2 UV(A) and 2.32 ꢂ
Fig. 1 Examples of absorbed (left) and surface functionalized (right)
QAC's.
0.242 J cmꢀ2 UV(V) and irradiance of 3.05 ꢁ 10ꢀ2 ꢂ 1.90 ꢁ 10ꢀ3
1510 | J. Mater. Chem. B, 2014, 2, 1509–1520
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
Journal of Materials Chemistry B
W cmꢀ2 UV(A) and 1.90 ꢁ 10ꢀ2 ꢂ 1.90 ꢁ 10ꢀ3 W cmꢀ2 UV(V). 275.0838; found, 275.0841. (This compound was previously
Dose and irradiance measurements were measured with an EIT reported by Saettone et al., but not fully characterized.)38
Power Puck.
4-(3-Iodopropoxy)benzophenone.37
4-(3-Bromopropyoxy)-
benzophenone (1.00 g: 3.13 mmol) and NaI (1.41 g: 9.40 mmol)
were mixed in acetone (10 mL) under reux for 24 h. The crude
product was ltered off and recrystallized in toluene–hexanes
bis- (1 : 2) to afford a yellow coloured powder. Yield: 0.59 g (51%).
Synthesis of precursors for the dansyl quaternization reaction
Tetraethyl(((3-iodopropyl)azanediyl)bis(methylene))
(phosphonate).
A
mixture of 3-(bis((diethoxyphosphoryl)- Mp ¼ 72–74 ꢃC. 1H NMR (400 MHz, CDCl3, d): 7.85–7.80 (m, 2H:
methyl)amino)propyl methanesulfonate (1.0 g: 2.21 mmol) H1), 7.77–7.73 (m, 2H: H7), 7.56 (ddt, 1H, J ¼ 8.6 Hz, J ¼ 6.6 Hz,
and NaI (0.69 g: 4.6 mmol) in acetone (3 mL) were placed, with J ¼ 1.3 Hz: H3), 7.50–7.43 (m, 2H: H2), 6.99–6.89 (m, 2H: H8),
a magnetic stirring bar, into a 5 mL mW glass reaction tube and 4.13 (t, 2H, J ¼ 5.8 Hz: H10), 3.38 (t, 2H, J ¼ 6.7 Hz: H12), 2.35–
sealed. The reaction mixture was placed in microwave and, 2.27 (m, 2H: H11) ppm; 13C{1H} NMR (100 MHz, CDCl3, d):
with constant stirring, run at 100 ꢃC for 5 min. The yellow solid 195.54 (C5), 162.30 (C9), 138.24 (C4), 132.59 (C3), 131.94 (C7),
was transferred to a 100 mL round bottom ask and washed 130.39 (C6), 129.75 (C1), 128.21 (C2), 114.06 (C8), 67.52 (C10),
with acetone (50 mL). Volatiles were removed with the aid of 32.72 (C11), 2.13 (C12) ppm. HRMS-DART (m/z): [MH+] calcu-
rotary evaporation and the crude material diluted with brine lated for C16H15IO2, 367.0195 found, 367.0202.
(10 mL) and then extracted with CHCl3 (10 mL). The organic
4-(4-Bromobutoxy)benzophenone.37
1,4-Dibromobutane
layer was separated, dried over anhydrous MgSO4, ltered, (6.02 mL: 50.4 mmol), K2CO3 (3.49 g: 25.3 mmol) and 4-
and dried on a vacuum line and recovered as a yellow oil. hydroxybenzophenone (2.50 g: 12.6 mmol) were stirred in ACN
Yield: 0.80 g (75%). TLC (10% w/w NH4OH–acetone): Rf ¼ (20 mL) under reux for 24 h to give a crude product of 4-(4-
0.85. 1H NMR (400 MHz, CDCl3, d): 4.20–4.09 (m, 8H: H6), 3.24 bromobutoxy)benzophenone which was recrystallized in
(t, 2H, J ¼ 7.0 Hz: H5), 3.15 (d, 4H, J ¼ 8.7 Hz: H4), 2.89 (t, 2H, toluene–hexanes (1 : 2) to yield a pale yellow powder. Yield:
1
ꢃ
J ¼ 6.6 Hz: H3), 2.03–1.94 (m, 2H: H2), 1.33 (t, 12H, J ¼ 7.0 Hz: 3.84 g (91.6%). Mp ¼ 50–51 C. H NMR (400 MHz, CDCl3, d):
2
H1); 13C{1H} NMR (100 MHz, CDCl3, d): 61.92 (t, JC–P ¼ 3.4 7.81 (d, 2H, J ¼ 8.8: H1), 7.74 (d, 2H, J ¼ 7.2: H7), 7.55 (t, 1H, J ¼
Hz, C6), 55.08 (C3), 49.46 (C4), 31.09 (C5), 30.96 (C2), 16.49 (t, 7.4: H3), 7.46 (t, 2H, J ¼ 7.7: H2), 6.94 (d, 2H, J ¼ 8.8 Hz: H8),
3JC–P ¼ 2.9 Hz: C1); 31P{1H} NMR (121.45 MHz, CDCl3, d): 4.07 (t, 2H, J ¼ 5.9 Hz: H10), 3.50 (t, 2H, J ¼ 6.5 Hz: H13), 2.14–
24.79 ppm.
4-(3-Bromopropyoxy)benzophenone.36,37
2.05 (m, 2H: H11), 2.04–1.95 (m, 2H: H12) ppm; 13C{1H} NMR
1,3-Dibromopro- (100 MHz, CDCl3, d): 195.53 (C5), 162.52 (C9), 138.29 (C4),
pane (6.14 mL: 60.5 mmol), K2CO3 (4.18 g: 30.2 mmol) and 4- 132.59 (C3), 131.90 (C7), 130.20 (C6), 129.73 (C1), 128.20 (2),
hydroxybenzophenone (3.0 g: 15.1 mmol) were stirred in ACN 113.99 (C8), 67.13 (C10), 33.29 (C13), 29.36 (C12), 27.77 (C11)
(20 mL) under reux for 24 h. The crude product was recrys- ppm. HRMS-DART (m/z): [MH+] calculated for C17H17BrO2,
tallized in toluene–hexanes (1 : 2) to give an off white coloured 333.0490 found, 333.0486.
powder. Yield: 3.22 g (66.7%). Mp ¼ 52–53 ꢃC. 1H NMR (400
4-(4-Iodobutoxy)benzophenone.39 4-(4-Bromobutoxy)benzo-
MHz, CDCl3, d): 7.83 (d, 2H, J ¼ 8.7 Hz: H1), 7.77 (d, 2H, J ¼ 8.3 phenone (1.00 g: 3.00 mmol) and NaI (0.900 g: 6.00 mmol) were
Hz: H7), 7.58 (t, 1H, J ¼ 7.4 Hz: H3), 7.48 (t, 2H, J ¼ 7.7 Hz: H2), mixed in acetone (10 mL) under reux for 24 h to give crude
6.98 (d, 2H, J ¼ 8.7 Hz: H8), 4.20 (t, 2H, J ¼ 5.8 Hz: H10), 3.63 (t, product of 4-(4-iodobutoxy)benzophenone which was recrystal-
2H, J ¼ 6.3 Hz: H12), 2.37 (q, 2H, J ¼ 6.0 Hz: H11) ppm; 13C{1H} lized in toluene–hexanes (1 : 2) to afford a pale yellow powder.
NMR (100 MHz, CDCl3, d): 195.51 (C5), 162.30 (C9), 138.23 (C4), Yield: 1.03 g (90.2%). Mp ¼ 84–86 ꢃC. 1H NMR (400 MHz, CDCl3,
132.58 (C3), 131.94 (C7), 130.36 (C6), 129.74 (C1), 128.21 (C2), d): 7.80 (d, 2H, J ¼ 8.7: H1), 7.74 (d, 2H, J ¼ 7.3: H7), 7.54 (t, 1H,
114.04 (C8), 65.53 (C10), 32.13 (C12), 29.74 (C11) ppm. This J ¼ 7.3: H3), 7.47 (t, 2H, J ¼ 7.6: H2), 6.93 (d, 2H, J ¼ 8.8 Hz: H8),
compound was previously prepared by Krichelodorf et al., but 4.06 (t, 2H, J ¼ 5.9 Hz: H10), 3.26 (t, 2H, J ¼ 6.7 Hz: H13), 2.10–
not characterized by NMR.38 HRMS-DART (m/z): [MH+] calcu- 2.02 (m, 2H: H11), 2.00–1.90 (m, 2H: H12) ppm; 13C{1H} NMR
lated for C16H15BrO2, 319.0334; found, 319.0329.
(100 MHz, CDCl3, d): 195.54 (C5), 162.52 (C9), 138.29 (C4),
1-Bromo-3-chlor- 132.59 (C3), 131.90 (C7), 130.20 (C6), 129.73 (C1), 128.20 (C2),
4-(3-Chloropropoxy)benzophenone.37,38
opropane (5.00 mL: 50.4 mmol), K2CO3 (3.49 g: 25.3 mmol) and 113.99 (C8), 66.93 (C10), 30.06 (C12), 30.02 (C11), 6.15 (C13)
4-hydroxybenzophenone (2.50 g: 12.6 mmol) were stirred in ppm. HRMS-DART (m/z): [MH+] calculated for C17H17IO2,
ACN (20 mL) under reux for 24 h. The crude product was 381.0351 found, 381.0339. (This data is in good agreement with
ltered off and recrystallized in toluene–hexanes to yield an off previously reported values.)39
white coloured powder. Yield: 1.21 g (34.9%). Mp ¼ 60–61 ꢃC. 1H
4-(6-Bromohexoxy)benzophenone.38,39 1,6-Dibromohexane
NMR (400 MHz, CDCl3, d): 7.83 (d, 2H, J ¼ 8.4 Hz: H1), 7.76 (d, (6.21 mL: 40.4 mmol), K2CO3 (2.79 g: 20.2 mmol) and 4-
2H, J ¼ 7.2 Hz: H7), 7.56 (t, 1H, J ¼ 7.3 Hz: H3), 7.48 (t, 2H, J ¼ hydroxybenzophenone (2.00 g: 10.1 mmol) were stirred in ACN
7.5 Hz: H2), 6.96 (d, 2H, J ¼ 8.4 Hz: H8), 4.23–4.16 (m, 2H: H10), (20 mL) under reux for 24 h to give a crude product of 4-(6-
3.76 (t, 2H, J ¼ 5.9 Hz: H12), 2.28 (t, 2H, J ¼ 11.4 Hz: H11) ppm; bromohexoxy)benzophenone which was recrystallized in
13C{1H} NMR (100 MHz, CDCl3, d): 195.53 (C5), 162.34 (C9), toluene–hexanes (1 : 2) to yield a white coloured powder. Yield:
1
ꢃ
138.25 (C4), 132.58 (C3), 131.93 (C7), 130.37 (C6), 129.74 (C1), 1.50 g (42.7%). Mp ¼ 62–64 C. H NMR (400 MHz, CDCl3, d):
128.21 (C2), 114.04 (C8), 64.50 (C10), 41.30 (C12), 32.07 (C11) 7.84–7.80 (m, 2H: H1), 7.77–7.41 (m, 2H: H7), 7.59–7.54 (m, 1H:
ppm. HRMS-DART (m/z): [MH+] calculated for C16H15ClO2, H3), 7.50–7.44 (m, 2H: H2), 6.97–6.93 (m, 2H: H8), 4.05 (t, 2H,
This journal is © The Royal Society of Chemistry 2014
J. Mater. Chem. B, 2014, 2, 1509–1520 | 1511

View Article Online
Journal of Materials Chemistry B
Paper
J ¼ 6.4 Hz: H10), 3.43 (t, 2H, J ¼ 6.8 Hz: H15), 1.95–1.81 (m, 4H: (25 mL) of 80% EtOH–H2O. Yield: 12.1 g (97%). Mp ¼ 122–124 ꢃC.
(H11, H12)), 1.55–1.52 (m, 4H: (H13, H14)) ppm; 13C{1H} NMR TLC (5% w/w NH4OH–acetone), Rf ¼ 0.72. UV-Vis (MeOH, 1 ꢁ
1
(100 MHz, CDCl3, d): 195.64 (C5), 162.96 (C9), 138.22 (C4), 10ꢀ3 M), lAbs max ¼ 516 nm, 3 ¼ 447 Mꢀ1 cmꢀ1. H NMR (400
132.57 (C3), 131.07 (C7), 129.98 (C6), 129.78 (C1), 128.21 (C2), MHz, CDCl3, d): 8.52 (d, 1H, J ¼ 8.5 Hz: H8), 8.31 (d, 1H, J ¼ 8.6
113.98 (C8), 67.99 (C10), 34.02 (C15), 32.74 (C14), 29.15 (C13), Hz: H5), 8.23 (dd, 1H, 1J ¼ 1.2 Hz, 2J ¼ 7.3 Hz: H10), 7.58–7.50 (m,
27.87 (C11), 25.59 (C12) ppm. HRMS-DART (m/z): [MH+] calcu- 2H: H4, H9), 7.17 (d, 1H, J ¼ 7.5: H3), 2.94 (t, 2H, J ¼ 5.5 Hz: H13),
lated for C19H21BrO2, 361.0803; found, 361.0796. (This data is in 2.88 (s, 6H: H1), 2.21 (t, 2H, J ¼ 5.5 Hz: H15), 2.12 (s, 6H: H16),
good agreement with previously reported values.)39
1.58–1.52 (m, 2H: H14) ppm; 13C{1H} NMR (100 MHz, CDCl3, d):
4-(6-Chlorohexoxy)benzophenone.37 1-Bromo-6-chlorohex- 151.90 (C2), 134.77 (C11), 129.98 (C6), 128.89 (C8), 129.71 (C4),
ane (2.77 mL: 13.9 mmol), K2CO3 (3.49 g: 25.2 mmol) and 4- 129.65 (C9), 128.07 (C10), 123.17 (C5), 119.03 (C7), 115.00 (C3),
hydroxybenzophenone (2.50 g: 12.6 mmol) were stirred in ACN 59.58 (C15), 45.42 (C1, C16), 44.54 (C13), 24.61 (C14) ppm. HRMS-
(20.0 mL) under reux for 24 h to give a crude product of 4-(6- DART (m/z): [M+] calculated for C17H26N3O2S1, 336.1736; found,
chlorohexoxy)benzophenone which was recrystallized in 336.1745. (This compound has also been prepared on a 25 g, 92.6
toluene–hexanes (1 : 2) to yield an off white coloured powder. mmol scale.)
Yield: 3.07 g (76.8%). Mp ¼ 65–66 ꢃC. 1H NMR (400 MHz, CDCl3,
d): 7.81 (d, 2H, J ¼ 8.7 Hz: H1), 7.75 (d, 1H, J ¼ 7.4 Hz: H7), 7.55
General procedure for the synthesis of dansyl quaternary
ammonium salts
(t, 2H, J ¼ 7.4 Hz: H3), 7.47 (t, 2H, J ¼ 7.6 Hz: H2), 6.94 (d, 2H,
J ¼ 8.7 Hz: H8), 4.04 (t, 2H, J ¼ 6.4 Hz: H10), 3.55 (t, 2H, J ¼ 6.6
Hz: H15), 1.85–1.80 (m, 4H: H11, H12), 1.55–1.51 (m, 4H: H13, In a glass screw cap vial 5-(dimethylamino)-N-(3-(dimethyla-
H14) ppm; 13C{1H} NMR (100 MHz, CDCl3, d): 195.55 (C5), mino)propyl)naphthalene-1-sulfonamide 1 (1.0 equiv.) and the
162.77 (C9), 138.35 (C4), 132.58 (C3), 131.86 (C7), 130.01 (C6), appropriate alkyl halide (1.0–2.0 equiv.) were dissolved in ACN
129.72 (C1), 130.01 (C2), 114.01 (C8), 68.01 (C10), 44.98 (C15), or EtOH (0.5–1.0 M). The resultant solution was stirred at
32.48 (C14), 28.98 (C13), 26.61 (C11), 25.38 (C12) ppm. HRMS- reux (4–24 h) until TLC analysis showed the disappearance of
DART (m/z): [MH+] calculated for C19H21ClO2, 317.1308; found, the starting materials (EtOAc–hexanes 1 : 4). The residue was
317.1311.
then precipitated from the resultant solution by the addition
4-(6-Iodohexoxy)benzophenone.39 4-(3-Bromohexoxy)benzo- of cold Et2O (5 ꢁ 5 mL) followed by decanting the solvent and
phenone (0.500 g: 1.38 mmol) and NaI (0.622 g: 4.15 mmol) were placing the vial under high vacuum (ꢄ1 h) to afford the desired
mixed in acetone (10.0 mL) under reux for 24 h to give crude product.
product of 4-(6-iodohexoxy)benzophenone which was recrystal-
3-(5-(Dimethylamino)naphthalene-1-sulfonamido)-N,N-
lized in toluene–hexanes (1 : 2) to afford an off white coloured dimethyl-N-(3-(trimethoxysilyl)propyl)propan-1-aminium chlo-
1
ꢃ
powder. Yield: 0.480 g (85.0%). Mp ¼ 55–57 C. H NMR (400 ride 2. To a ame dried 25 mL round bottom ask with a reux
MHz, CDCl3, d): 7.77 (m, 4H: H1, H7), 7.51 (m, 3H: H2, H3), 6.95 condenser connected to an inert atmosphere manifold, ACN
(m, 2H: H8), 4.05 (m, 2H: H10), 3.21 (m, 2H: H15), 1.85 (m, 4H: (20 mL) was added followed by 5-(dimethylamino)-N-(3-(dime-
H11, H12), 1.55 (m, 4H: H13, H14) ppm; 13C{1H} NMR (CDCl3, thylamino)propyl)naphthalene-1-sulfonamide (3.35 g: 10
100 MHz): d 195.61 (C5), 162.62 (C9), 138.35 (C4), 132.57 (C3), mmol). While stirring, (3-chloropropyl)trimethoxysilane (5 mL:
131.85 (C7), 130.00 (C6), 129.72 (C1), 128.17 (C2), 113.89 (C8), 25 mmol) was added via syringe. The solution was stirred for 48
ꢃ
68.13 (C10), 33.12 (C14), 30.17 (C11), 29.04 (C13), 25.02 (C12), h at 110 C, with the solution turning to yellow-brownish col-
6.85 (C15) ppm. (This data is in good agreement with previously oured oil. The oil was then precipitated in cold (1 : 1) DCM–Et2O
reported values.)39
mixture, forming two layers; a gummy layer and a white liquid
5-(Dimethylamino)-N-(3-(dimethylamino)propyl)naphthalene- layer. The white liquid layer was separated inside a 10 mL
1-sulfonamide 1.40,41 To a ame dried 500 mL round bottom ask syringe and collected in a second 25 mL round bottom ask; the
with a reux condenser connected to an inert atmosphere gummy layer was dissolved using DCM and collected in a 25 mL
manifold, anhydrous DCM (300 mL) was added followed by round bottom ask. Excess DCM was evaporated using a rotary
dansyl chloride (10.0 g: 37.07 mmol), Et3N (8 mL: 55.6 mmol). evaporator resulting in the recovery of a yellow coloured solid,ꢀ23.
While the solution was stirring at room temperature (23 ꢂ 2 ꢃC), Yield: 3.85 g (72.0%). Mp ¼ 85–87 ꢃC. UV-Vis (MeOH, 1 ꢁ 10
1
3-(dimethylamino)propylamine (7.0 mL: 55.6 mmol) was added M), lAbs max ¼ 340 nm, 3 ¼ 413 Mꢀ1 cmꢀ1. H NMR (400 MHz,
drop wise via an inert syringe resulting in a colour change from CDCl3, d): 8.48 (d, 2H, J ¼ 8.6 Hz: H8, H5), 8.37 (s, 1H, H12), 8.19
orange to lime-green. Aer stirring for 1 h, HCl (g) was bubbled (d, 1H, J ¼ 7.3 Hz: H10), 7.59 (t, 1H, J ¼ 7.9 Hz: H4), 7.49 (t, 1H, J
through the solution until a pH of 2 was achieved. The resulting ¼ 8.2 Hz: H9), 7.13 (d, 1H, J ¼ 7.6 Hz: H3), 3.57–3.52 (m, 2H:
mixture was evaporated to dryness, re-dissolved in saturated H17), 3.49 (s, 9H: H20), 3.27–3.20 (m, 2H: H15), 3.10 (s, 6H:
brine H2O (100 mL) and brought to pH 11 with 6 N NaOH (15 mL) H16), 3.08–3.03 (m, 2H: H13), 2.84 (s, 6H: H1), 2.01–1.90 (m, 2H:
at 0 ꢃC until a white-yellow coloured precipitate was observed. H14), 1.71–1.60 (m, 2H: H18), 0.54 (t, 2H, J ¼ 7.8 Hz: H19) ppm;
The mixture was refrigerated overnight enhancing further 13C{1H} NMR (100 MHz, CDCl3, d): 151.70 (C2), 135.06 (C11),
precipitation of product. The precipitate was ltered and washed 130.18 (C4), 129.75 (C6), 129.58 (C8), 128.93 (C9), 128.53 (C10),
(2 ꢁ 30 mL) with H2O and the ltrate extracted with DCM (500 123.35 (C5), 119.45 (C7), 115.14 (C3), 65.62 (C15), 62.27 (C17),
mL) and evaporated to dryness to afford a white coloured solid, 1. 50.79 (C16), 50.68 (C20), 45.40 (C1), 39.81 (C13), 26.00 (C14),
The crude sample was recrystallized using a minimum volume 16.16 (C18), 5.35 (C19) ppm; 29Si{1H} NMR (79.4 MHz, CD3OD,
1512 | J. Mater. Chem. B, 2014, 2, 1509–1520
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
Journal of Materials Chemistry B
d): ꢀ68.86 ppm. HRMS-DART (m/z): [M+ ꢀ Clꢀ, –CH3], calcu- anhydrous DCM (5 mL). To the clear solution, with stirring, was
lated for C23H40ClN3O5SSi, 484.2314; found 484.2315.
added trimethylsilyl bromide (0.23 mL: 1.76 mmol) through a
3-(Diethoxyphosphoryl)-N-(3-(5-(dimethylamino)naphthalene- rubber septum via syringe and the reaction was then stirred at
1-sulfonamido)propyl)-N,N-dimethylpropan-1-aminium bromide room temperature overnight. Completion of the reaction was
3a. To a stirred solution of 1 (2.06 g: 6.13 mmol) in reuxing monitored by 31P NMR, aer which the reaction was quenched
ACN (15 mL) was added diethyl(3-bromopropyl)phosphonate with EtOH (10 mL) and stirred for 1 h followed by the addition
(2.40 g: 9.2 mmol) via syringe, and the vial was capped and of H2O (1 mL). Volatiles were removed under high vacuum and
reuxed for 20 h. To purify, the mixture was rst triturated, the crude product was rst triturated then washed with Et2O
washed with Et2O (2 ꢁ 40 mL) to remove any unreacted starting (2 ꢁ 10 mL) to remove brown colored impurities. Further
material followed by drying under high vacuum overnight to purication entailed extraction with NH4OH–H2O (1 : 10, 10
afford 3a as a yellow coloured solid. Yield: (3.64 g: 90%). Mp ¼ mL) and washed with Et2O (1 ꢁ 5 mL). The aqueous uorescent
ꢀ3
ꢃ
37–39 C. UV-Vis (MeOH, 1 ꢁ 10 M), lAbs max ¼ 334 nm, 3 ¼ layer was evaporated from ACN (50 mL) to give 3c as a light
505 Mꢀ1 cmꢀ1. 1H NMR (400 MHz, CDCl3, d): 8.51 (d, 1H, J ¼ 8.3 yellow coloured solid. Yield: 0.25 g: (79%). Mp ¼ 166–168 C;
ꢃ
Hz: H8), 8.43 (d, 1H, J ¼ 8.6 Hz: H5), 8.20 (dd, 1H, 1J ¼ 1.0 Hz, UV-Vis (MeOH, 1 ꢁ 10ꢀ3 M), lAbs max ¼ 342 nm, 3 ¼ 449 Mꢀ1
2J ¼ 7.3 Hz: H10), 7.71 (s, 1H: H12), 7.59 (t, 1H, J ¼ 8.4 Hz: H9), cmꢀ1. H NMR (400 MHz, D2O, d): 8.58 (d, 1H, J ¼ 8.5 Hz: H8),
1
7.50 (t, 1H, J ¼ 7.3 Hz: H4), 7.16 (d, 1H, J ¼ 7.4 Hz: H3), 4.11–4.02 8.35 (d, 1H, J ¼ 8.5 Hz: H5), 8.23 (d, 1H, J ¼ 7.0 Hz: H10), 7.70–
(m, 4H: H20), 3.67–3.56 (m, 4H: H15, H17), 3.17 (s, 6H: H16), 7.58 (m, 2H: H4, H9), 7.31 (d, 1H, J ¼ 7.5 Hz: H3), 3.32 (s, 6H:
3.10–2.99 (m, 2H: H13), 2.86 (s, 6H: H1), 2.10–1.95 (m, 4H: H14, H16), 3.30–3.22 (m, 2H: H17 overlap), 3.19–3.11 (m, 2H: H15),
H18), 1.89–1.77 (m, 2H: H19), 1.28 (t, 6H, J ¼ 7.1 Hz: H21) ppm; 2.97 (t, 2H, J ¼ 6.0 Hz: H13), 2.89 (s, 6H: H1), 1.93–1.86 (m, 4H:
13C{1H} NMR (100 MHz, CDCl3, d): 151.79 (C2), 134.62 (C11), H14, H18), 1.57–1.49 (m, 2H, H19) ppm; 13C{1H} NMR (100 MHz,
130.29 (C4), 129.79 (C6), 129.47 (C8), 129.34 (C9), 128.60 (C10), D2O, d): 133.80 (C2), 131.15 (C11), 130.15 (C6), 129.76 (C8), 128.99
123.28 (C5), 119.28 (C7), 115.30 (C3), 62.23–62.16 (overlap, C15, (C4), 128.61 (C9), 128.40 (C10), 124.54 (C5), 119.81 (C7), 116.59
3
C17, C20), 51.31 (C16), 45.43 (C1), 39.73 (C13), 24.75–22.83 (C3), 64.32 (d, JC–P ¼ 18.8 Hz, C17), 61.33 (C15), 53.99 (C16),
2
1
(C14, C18, C19), 16.45 (d, J ¼ 6.0 Hz: C21) ppm; 31P{1H} NMR 45.08 (C1), 39.04 (C13), 24.77 (d, JC–P ¼ 136.1 Hz, C19), 21.96
(121.45 MHz, CDCl3, d): 29.29 ppm. HRMS-DART (m/z): [M+ ꢀ (C14), 16.85 (d, JC–P ¼ 3.2 Hz, C18) ppm; 31P{1H} NMR (121.45
2
Brꢀ] calculated for C24H41BrN3O5P1S1, 514.2504; found, MHz, D2O, d): 20.99 ppm. HRMS-ESI-TOF (m/z): [M+ ꢀ Brꢀ]
514.2519.
calculated for C20H33BrN3O5P1S1, 458.1873; found, 458.1868.
3-(Diisopropoxyphosphoryl)-N-(3-(5-(dimethylamino) naph-
3-(Bis((diethoxyphosphoryl)methyl)amino)-N-(3-(5-(dimethy-
thalene-1-sulfonamido)propyl)-N,N-dimethylpropan-1-aminium lamino)naphthalene-1-sulfonamido)propyl)-N,N-dimethylpro-
bromide 3b. To a stirred solution of 1 (0.5 g: 1.5 mmol) in pan-1-aminium iodide 4. To a stirred solution of 1 (0.658 g:
reuxing ACN (3 mL) was added diisopropyl(3-bromopropyl) 1.35 mmol) in reuxing ACN (3 mL) was added tetraethyl (((3-
phosphonate (0.46 g: 1.6 mmol) via syringe, and the vial was iodopropyl)azanediyl)bis(methylene))bis(phosphonate) (0.658
capped and reuxed for 7 h. To purify, the mixture was rst g: 1.35 mmol), and the vial was capped and reuxed for 7 h. To
triturated, washed with Et2O (2 ꢁ 15 mL) to remove any purify, the mixture was triturated, washed with Et2O (2 ꢁ 15 mL)
unreacted starting material, followed by drying under high to remove any unreacted starting material followed by drying
vacuum overnight to afford 3b as a yellow coloured soliꢀd3. under high vacuum overnight to afford 4 as a yellow solid. Yield:
Yield: 0.653 g: (70%). Mp ¼ 36–38 ꢃC; UV-Vis (MeOH, 1 ꢁ 10
0.626 g: (60%). Mp ¼ 40–42 ꢃC; UV-Vis (MeOH, 1 ꢁ 10ꢀ3 M), lAbs
1
M), lAbs max ¼ 340 nm, 3 ¼ 519 Mꢀ1 cmꢀ1. H NMR (400 MHz,
¼ 340 nm, 3 ¼ 526 Mꢀ1 cmꢀ1. 1H NMR (400 MHz, CDCl3, d):
max
CDCl3, d): 8.50 (d, 1H, J ¼ 8.3 Hz: H8), 8.43 (d, 1H, J ¼ 8.6 Hz: 8.48–8.38 (m, 2H: H8), 8.37–8.29 (m, 1H: H5), 8.19–8.12 (m, 1H:
1
2
H5), 8.22 (dd, 1H, J ¼ 1.0 Hz, J ¼ 7.3 Hz: H10), 7.75 (s, 1H: H10), 7.72 (s, 1H: H12), 7.56–7.38 (m, 2H: H4, H9), 7.15 (m, 1H:
H12), 7.59 (t, 1H, J ¼ 8.4 Hz: H9), 7.49 (t, 1H, J ¼ 7.3 Hz: H4), H2), 4.16–3.97 (m, 8H: H21), 3.62–3.25 (m, 4H: H15, H17), 3.05–
7.15 (d, 1H, J ¼ 7.4 Hz: H3), 4.68–4.56 (m, 2H: H20), 3.66–3.49 2.85 (s, 6H: H16), 3.10–2.91 (m, 8H: H19, H20, H13), 2.81 (s, 6H,
(m, 4H: H15, H17), 3.16 (s, 6H: H16), 3.09–2.97 (m, 2H: H13), H1), 1.99–1.75 (m, 4H: H14, H18), 1.25 (t, 12H, J ¼ 7.0 Hz: H22)
2.85 (s, 6H: H1), 2.05–1.90 (m, 4H: H14, H18), 1.80–1.69 (m, 2H: ppm; 13C{1H} NMR (100 MHz, CDCl3, d): 151.85 (C2), 135.16
H19), 1.26 (t, 12H, J ¼ 7.1 Hz: H21) ppm; 13C{1H} NMR (100 (C11), 130.18 (C6), 129.76 (C8), 129.47 (C4), 129.12 (C9), 128.38
MHz, CDCl3, d): 151.79 (C2), 134.62 (C11), 130.31 (C4), 129.87 (C10), 123.34 (C5), 119.34 (C7), 115.19 (C3), 62.74 (C15), 62.24 (t,
(C6), 129.49 (C8), 129.31 (C9), 128.64 (C10), 123.28 (C5), 119.28 2JC–P ¼ 3.5 Hz: C21), 61.84 (C17), 53.78 (C19), 51.65 (C16), 50.49
(C7), 115.30 (C3), 70.69 (C20), 62.23–62.16 (overlap, C15, C17), (C20), 45.38 (C1), 39.61 (C13), 22.79 (C14), 21.22 (C18), 16.51 (d,
51.19 (C16), 45.42 (C1), 41.80 (C13), 39.60 (C21), 33.76 (C19), 2JC–P ¼ 2.5 Hz: C22) ppm; 31P{1H} NMR (121.45 MHz, CDCl3, d):
24.08 (C14, C18) ppm; 31P{1H} NMR (121.45 MHz, CDCl3, d): 24.42 ppm. HRMS-ESI-TOF (m/z): [MH+ ꢀ Iꢀ] calculated for
27.32 ppm. HRMS-ESI-TOF (m/z): [M+ ꢀ Brꢀ] calculated for
C
30H55IN4O8P2S1, 693.3210; found, 693.3213.
3-(Acetylthio)-N-(3-(5-(dimethylamino)naphthalene-1-sulfona-
C
26H45BrN3O5P1S1, 542.2813; found, 542.2815.
3-(5-(Dimethylamino)naphthalene-1-sulfonamido)-N,N- mido)propyl)-N,N-dimethylpropan-1-aminium chloride 5. To a
dimethyl-N-(3-phosphonopropyl)propan-1-aminium bromide stirred solution of 1 (1.0 g: 2.98 mmol) in reuxing EtOH (4 mL)
3c. Inside a ame dried and evacuated 20 mL screw cap vial was added 3-chloropropylthioacetate (90%) (0.65 mL: 4.9 mmol)
N-(3-(diethoxyphosphoryl)propyl)-N,N-dimethyloctadecan-1- via syringe, and the vial capped and reuxed for 24 h. To purify,
ammonium bromide (0.35 g: 0.58 mmol) was dissolved in the mixture was rst triturated, washed with Et2O (2 ꢁ 15 mL) to
This journal is © The Royal Society of Chemistry 2014
J. Mater. Chem. B, 2014, 2, 1509–1520 | 1513

View Article Online
Journal of Materials Chemistry B
Paper
remove any unreacted starting material followed by drying 151.90 (C2), 138.16 (C11), 134.75 (C25), 132.57 (C6), 131.93
under high vacuum overnight to afford 5 as a yellow coloured (C28), 130.00 (C23), 129.87 (C8), 129.72 (C22), 129.68 (C26),
ꢃ
solid. Yield: 1.1 g (63%). Mp ¼ 35–36 C. UV-Vis (MeOH, 1 ꢁ 129.62 (C4), 128.23 (C9), 128.20 (C10), 128.10 (C27), 123.17 (C5),
1
10ꢀ3 M), lAbs max ¼ 334 nm, 3 ¼ 439 Mꢀ1 cmꢀ1. H NMR (400 118.99 (C7), 115.01 (C3), 114.02 (C21), 64.48 (C17), 64.45 (C15),
MHz, CDCl3, d): 8.49 (d, 1H, J ¼ 8.4 Hz: H8), 8.43 (d, 1H, J ¼ 8.5 59.49 (C19), 45.41 (C16), 44.47 (C1), 41.29 (C13), 32.04 (C18),
Hz: H5), 8.18 (d, 1H, J ¼ 7.3 Hz: H10), 7.57 (t, 1H, J ¼ 8.0 Hz: H4), 24.63 (C14) ppm. HRMS-ESI-TOF (m/z): [M+ ꢀ Clꢀ] calculated for
7.49 (t, 1H, J ¼ 8.2 Hz: H9), 7.15 (d, 1H, J ¼ 7.5 Hz: H3), 3.57–3.48
(m, 2H: H15), 3.40–3.32 (m, 2H: H17), 3.10 (s, 6H: H16), 3.05–
C
33H40ClN3O4S, 574.2751; found, 574.2734.
3-(4-Benzoylphenoxy)-N-(3-(5-(dimethylamino)naphthalene-1-
2.98 (m, 2H: H13), 2.86 (s, 6H, H1), 2.83–2.77 (m, 2H: H19), 2.28 sulfonamido)propyl)-N,N-dimethylpropan-1-ammonium iodide
(s, 3H: H21), 2.03–1.85 (m, 4H: H14, H18) ppm; 13C{1H} NMR 6c.37 To a stirred solution of compound 1 (0.252 g: 0.750 mmol)
(100 MHz, CDCl3, d): 195.80 (C21), 149.79 (C2), 134.73 (C11), and 4-(3-iodopropoxy)benzophenone (0.250 g: 0.680 mmol)
ꢃ
130.34 (C4), 129.67 (C6), 129.43 (C8), 128.32 (C9), 128.71 (C10), were dissolved in ACN (2 mL) and le to stir in a 100 C sand
124.64 (C5), 123.52 (C7), 115.45 (C3), 62.92 (C15), 62.73 (C17), bath for 24 h. The resultant residue was precipitated using cold
55.14 (C16), 45.32 (C1), 42.90 (C13), 30.77 (C21), 25.57 (C19), Et2O (4 mL) to afford the desired product 6c as a yellow coloured
23.16 (C18), 23.00 (C14) ppm. HRMS-ESI-TOF (m/z): [M+ ꢀ Clꢀ] powder. Yield: 0.267 g: (56%) Mp ¼ 73–75 ꢃC. 1H NMR (400
calculated for C22H34ClN3O3S2, 452.2036; found, 452.2037.
MHz, CDCl3, d): 8.49–8.39 (m, 2H: H5, H10), 8.18 (d, 1H, J ¼ 7.7
3-(4-Benzoylphenoxy)-N-3-((5-(dimethylamino)naphthalene-1- Hz: H8), 7.75–7.65 (m, 5H: H28, H22, H12, H9), 7.59–7.49 (m,
sulfonamido)propyl)-N,N-dimethylpropan-1-aminium bromide 2H: H27), 7.48–7.38 (m, 3H: H26, H4), 7.09 (d, 1H, J ¼ 7.6 Hz:
6a.37 To a stirred solution of compound 1 (0.5 g: 1.5 mmol) in 1H, H3), 6.85 (d, 2H, J ¼ 7.4 Hz: H21), 4.05–3.95 (m, 2H: H19),
reuxing ACN (4 mL) was added 4-(3-bromopropoxy)benzo- 3.65–3.56 (m, 4H: H15, H17), 3.15 (s, 6H: H16), 3.11–3.04 (m,
phenone (0.72 g: 2.25 mmol) via syringe, and the vial was cap- 2H: H13), 2.80 (s, 6H: H1), 2.23–2.10 (m, 2H: H14), 2.05–1.93 (m,
ped and reuxed for 24 h. To purify, the mixture was rst 2H: H18) ppm; 13C{1H} NMR (100 MHz, CDCl3, d): 195.45 (C24),
triturated and washed with Et2O (2 ꢁ 15 mL) to remove any 161.68 (C20), 151.88 (C2), 137.75 (C11), 134.33 (C25), 132.53
unreacted starting material followed by drying under high (C6), 132.45 (C28), 132.04 (C23), 130.55 (C8), 129.74 (C22),
vacuum overnight and recovered 6a as a yellow coloured 129.29 (C26), 129.27 (C4), 128.91 (C9), 128.26 (C10), 128.10
powder. Yield: 0.91 g (93%). Mp ¼ 75–76 ꢃC; UV-Vis (MeOH, 1 ꢁ (C27), 123.03 (C5), 118.94 (C7), 115.30 (C3), 113.80 (C21), 68.72
10ꢀ3 M), lAbs max ¼ 335 nm, 31 ¼ 524 Mꢀ1 cmꢀ1, lAbs max ¼ 288 (C17), 64.00 (C15), 58.43 (C19), 51.42 (C16), 45.37 (C1), 39.03
nm, 32 ¼ 327 Mꢀ1 cmꢀ1. 1H NMR (400 MHz, CDCl3, d): 8.49–8.43 (C13), 22.99 (C18), 18.42 (C14) ppm. HRMS-ESI-TOF (m/z): [M+ ꢀ
(m, 2H: H5, H10), 8.18 (d, 1H, J ¼ 7.3 Hz: H8), 7.76–7.68 (m, 5H: Iꢀ] calculated for C33H40IN3O4S, 574.2734; found, 574.2753.
H28, H22, H12, H9), 7.59–7.52 (m, 2H: H27), 7.47–7.42 (m, 3H:
4-(4-Benzoylphenoxy)-N-(3-(5-(dimethylamino)naphthalene-1-
H26, H4), 7.07 (d, 1H, J ¼ 7.6 Hz: H3), 6.82 (d, 2H, J ¼ 8.8 Hz: sulfonamido)propyl)-N,N-dimethylbutan-1-ammonium bromide
H21), 4.00 (t, 2H, J ¼ 5.4 Hz: H19), 3.73–3.69 (m, 2H: H15), 3.62– 6d.37 To a stirred solution of compound 1 (0.240 g: 0.717 mmol)
3.59 (m, 2H: H17), 3.22 (s, 6H: H16), 3.11–3.03 (m, 2H: H13), and 4-(4-bromobutoxy)benzophenone (0.721 mmol, 0.240 g)
ꢃ
2.81 (s, 6H: H1), 2.29–2.09 (m, 2H: H14), 2.05–1.95 (m, 2H: H18) were dissolved in ACN (2 mL) and le to stir in a 100 C sand
ppm; 13C{1H} NMR (100 MHz, CDCl3, d): 195.47 (C24), 161.69 bath for 24 h. The resultant residue was precipitated using cold
(C20), 151.86 (C2), 137.99 (C11), 134.86 (C25), 132.42 (C6), Et2O (4 mL) to afford the desired product 6d. Yield: 0.168 g
1
ꢃ
132.06 (C28), 130.51 (C23), 130.37 (C8), 129.71 (C22), 129.44 (35.0%). Mp ¼ 73–75 C. H NMR (400 MHz, CDCl3, d): 8.51–
(C26), 129.23 (C4), 129.20 (C9), 128.71 (C10), 128.25 (C27), 8.44 (m, 2H: H5, H10), 8.19 (d, 1H, J ¼ 7.3 Hz: H8), 7.77–7.67 (m,
123.36 (C5), 119.39 (C7), 115.30 (C3), 114.15 (C21), 65.82 (C17), 5H: H29, H23, H9), 7.60–7.51 (m, 2H: H28), 7.48–7.42 (m, 3H:
64.50 (C15), 62.50 (C19), 51.37 (C16), 45.34 (C1), 39.87 (C13), H27, H4), 7.12 (d, 1H, J ¼ 7.6 Hz: H3), 6.90 (d, 2H, J ¼ 8.9 Hz:
22.90 (C18), 15.26 (C14) ppm. HRMS-ESI-TOF (m/z): [M+ ꢀ Brꢀ] H22), 4.06–3.97 (m, 2H: H20), 3.71–3.60 (m, 2H: H15), 3.56–3.43
calculated for C33H40BrN3O4S, 574.2749; found, 574.2734.
(m, 2H: H17), 3.16 (s, 6H: H16), 3.14–3.00 (m, 2H: H13), 2.82 (s,
3-(4-Benzoylphenoxy)-N-(3-(5-(dimethylamino)naphthalene-1- 6H: H1), 2.08–1.96 (m, 2H: H19), 1.94–1.65 (m, 4H: H18, H14)
sulfonamido)propyl)-N,N-dimethylpropan-1-ammonium chlo- ppm; 13C{1H} NMR (100 MHz, CDCl3, d): 195.56 (C25), 162.22
ride 6b.37 To a stirred solution of compound 1 (0.870 mmol: (C21), 151.63 (C2), 138.09 (C11), 134.73 (C26), 132.51 (C6),
0.291 g) and 4-(3-chloropropoxy)benzophenone (0.790 mmol: 132.00 (C29), 130.35 (C24), 130.18 (C8), 129.73 (C23), 129.46
0.250 g) were dissolved in ACN (2 mL) and le to stir in a 100 ꢃC (C27), 129.26 (C4), 128.90 (C9), 128.74 (C28), 128.23 (C10),
sand bath for 24 h. The resultant residue was precipitated using 123.44 (C5), 119.12 (C7), 114.87 (C3), 114.11 (C22), 67.23 (C17),
cold Et2O (4 mL) to afford the desired product 6b as a yellow 64.00 (C15), 61.66 (C20), 51.18 (C16), 45.39 (C1), 39.87 (C13),
coloured powder. Yield: 0.25 g (51.9%). Mp ¼ 73–75 ꢃC. 1H NMR 25.74 (C19), 23.00 (C14), 19.75 (C18) ppm. HRMS-ESI-TOF (m/z):
(400 MHz, CDCl3, d): 8.54–8.48 (m, 2H: H5, H10), 8.29 (d, 1H, J ¼ [M+ ꢀ Brꢀ] calculated for C34H42BrN3O4S, 588.2908; found,
7.3 Hz: H8), 7.77–7.67 (m, 5H: H28, H9, H22), 7.60–7.42 (m, 5H: 588.2890.
H27, H26, H4), 7.19–7.12 (m, 1H: H3), 7.00–6.92 (m, 2H: H21),
4-(4-Benzoylphenoxy)-N-(3-(5-(dimethylamino)naphthalene-1-
4.23–4.16 (m, 2H: H19), 3.79–3.72 (m, 2H: H15), 3.63–3.59 (m, sulfonamido)propyl)-N,N-dimethylbutan-1-ammonium iodide
2H: H17), 3.23 (s, 6H: H16), 2.81–2.79 (m, 2H: H13), 2.20 (s, 6H: 6e.37 To a stirred solution of compound 1 (0.201 g: 0.598 mmol)
H1), 2.32–2.28 (m, 2H: H14), 2.15–1.92 (m, 2H: H18) ppm; 13C and 4-(4-iodobutoxy)benzophenone (0.250 g: 0.658 mmol) were
{1H} NMR (100 MHz, CDCl3, d): 195.53 (C24), 162.33 (C20), dissolved in ACN (2 mL) and le to stir in a 100 ꢃC sand bath for
1514 | J. Mater. Chem. B, 2014, 2, 1509–1520
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
Journal of Materials Chemistry B
24 h. The resultant residue was precipitated using cold diethyl ppm; 13C{1H} NMR (100 MHz, CDCl3, d): 195.58 (C27), 162.76
ether (4 mL) to afford the desired product 6e as a yellow col- (C23), 151.89 (C2), 138.31 (C11), 134.74 (C28), 132.57 (C6),
oured powder. Yield: 0.244 g (56.9%). Mp ¼ 73–75 ꢃC. 1H NMR 132.53 (C31), 131.96 (C26), 130.01 (C8), 129.91 (C25), 129.70
(400 MHz, CDCl3, d): 8.49 (d, 1H, J ¼ 8.20 Hz: H5), 8.40 (d, 1H, (C30), 129.68 (C4), 128.62 (C9), 128.20 (C29), 128.17 (C10),
J ¼ 8.6 Hz: H10), 8.18 (d, 1H, J ¼ 7.3 Hz: H8), 7.77–7.70 (m, 5H: 123.17 (C5), 118.98 (C7), 115.02 (C3), 113.99 (C24), 67.99 (C17),
H29, H23, H9), 7.61–7.53 (m, 2H: H28), 7.50–7.42 (m, 3H: H27, 67.77 (C15), 59.44 (C22), 50.93 (C16), 45.41 (C1), 44.41 (C13),
H4), 7.12 (d, 1H, J ¼ 7.4 Hz: H3), 6.91 (d, 2H, J ¼ 8.6 Hz: H22), 32.46 (C21), 28.95 (C19), 26.59 (C20), 25.46 (C18), 24.64 (C14)
4.10–3.99 (m, 2H: H20), 3.86–3.54 (m, 2H: H15), 3.53–3.43 (m, ppm. HRMS-ESI-TOF (m/z): [M+
ꢀ
Clꢀ] calculated for
36H46ClN3O4S, 616.3221; found, 616.3203.
6-(4-Benzoylphenoxy)-N-(3-(5-(dimethylamino)naphthalene-1-
2H: H17), 3.14 (s, 6H: H16), 3.10–3.01 (m, 2H: H13), 2.84 (s, 6H:
H1), 2.09–1.78 (m, 6H: H19, H18, H14) ppm; 13C{1H} NMR (100
C
MHz, CDCl3, d): 195.45 (C25), 162.22 (C21), 151.92 (C2), 138.05 sulfonamido)propyl)-N,N-dimethylhexan-1-ammonium iodide
(C11), 134.37 (C26), 132.58 (C6), 132.51 (C29), 132.04 (C24), 6h.37 To a stirred solution of compound 1 (0.272 g: 0.366 mmol)
130.55 (C8), 130.19 (C24), 129.74 (C27), 129.32 (C24), 128.91 and 4-(6-iodohexoxy)benzophenone (0.136 g: 0.333 mmol) were
(C9), 128.25 (C28), 128.20 (C10), 123.62 (C5), 119.37 (C7), 115.53 dissolved in ACN (2 mL) and le to stir in a 100 ꢃC sand bath for
(C3), 114.20 (C22), 66.99 (C17), 64.41 (C15), 62.73 (C20), 51.39 24 h. The resultant residue was precipitated using cold Et2O
(C16), 45.40 (C1), 39.62 (C13), 29.81 (C19), 25.74 (C14), 19.77 (4 mL) to afford the desired product as a yellow coloured powder
(C18) ppm. HRMS-ESI-TOF (m/z): [M+ ꢀ Iꢀ] calculated for 6h. Yield: 0232 g (93.5%). Mp ¼ 67–68 C. H NMR (400 MHz,
1
ꢃ
C
34H42IN3O4S, 588.2890; found, 588.2904.
6-(4-Benzoylphenoxy)-N-(3-(5-(dimethylamino)naphthalene-1- H10), 8.20–8.17 (m, 1H: H8), 7.78–7.70 (m, 5H: H31, H25, H12,
CDCl3, d): 8.48 (d, 1H, J ¼ 8.5 Hz: H5), 8.41 (d, 1H, J ¼ 8.7 Hz:
sulfonamido)propyl)-N,N-dimethylhexan-1-ammonium bromide H9), 7.61–7.42 (m, 5H: H30, H29, H4), 7.13 (d, 1H, J ¼ 7.2 Hz:
6f.37 To a stirred solution of compound 1 (0.211 g: 0.629 mmol) H3), 6.90 (d, 2H, J ¼ 8.9 Hz: H24), 3.95 (t, 2H, J ¼ 6.3 Hz: H22),
and 4-(6-bromohexoxy)benzophenone (0.250 g: 0.692ꢃ mmol) 3.56–3.49 (m, 2H: H15), 3.33–3.29 (m, 2H: H17), 3.10 (s, 6H:
were dissolved in ACN (2 mL) and le to stir in a 100 C sand H16), 3.08–3.06 (m, 2H: H13), 2.83 (s, 6H: H1), 1.76–1.59 (m, 6H:
bath for 24 h. The resultant residue was precipitated using cold H21, H18, H14), 1.49–1.40 (m, 2H: H20), 1.36–1.24 (m, 2H: H19)
Et2O (4 mL) to afford the desired product 6f as a yellow coloured ppm; 13C{1H} NMR (100 MHz, CDCl3, d): 195.63 (C27), 162.69
1
ꢃ
powder. Yield: 0.385 g (87.8%). Mp ¼ 70–71 C. H NMR (400 (C23), 151.87 (C2), 138.21 (C11), 132.53 (C28), 131.94 (C6),
MHz, CDCl3, d): 8.49 (d, 1H, J ¼ 8.8 Hz: H5), 8.46 (d, 1H, J ¼ 8.7 131.76 (C31), 130.55 (C26), 129.92 (C8), 129.72 (C25), 129.45
Hz: H10), 8.21–8.19 (m, 1H: H8), 7.78–7.71 (m, 5H: H31, H25, (C30), 129.33 (C4), 128.89 (C9), 128.22 (C29), 128.18 (C10),
H12, H9), 7.60–7.53 (m, 2H: H30), 7.50–7.42 (m, 3H: H29, H4), 123.62 (C5), 119.36 (C7), 115.54 (C3), 114.11 (C24), 67.23 (C17),
7.13 (d, 1H, J ¼ 7.4 Hz: H3), 6.89 (d, 2H, J ¼ 8.4 Hz: H24), 3.90 (t, 64.65 (C15), 59.09 (C22), 51.42 (C16), 45.42 (C1), 39.22 (C13),
2H, J ¼ 6.4 Hz: H21), 3.70–3.58 (m, 2H: H15), 3.39–3.28 (m, 2H: 28.71 (C21), 25.69 (C19), 25.47 (C20), 22.96 (C18), 22.59 (C14)
H17), 3.15 (s, 6H: H16), 3.13–3.00 (m, 2H: H13), 2.87 (s, 6H: H1), ppm. HRMS-ESI-TOF (m/z): [M+
ꢀ
Iꢀ] calculated for
1.79–1.62 (m, 6H: H21, H18, H14), 1.57–1.41 (m, 2H: H20), 1.40–
1.28 (m, 2H: H19) ppm; 13C{1H} NMR (100 MHz, CDCl3, d):
C
36H46IN3O4S, 616.3217; found, 616.3203.
N-(3-(5-(Dimethylamino)naphthalene-1-Sulfonamido)propyl)-
195.58 (C27), 162.68 (C23), 151.21 (C2), 138.20 (C11), 134.94 N,N-dimethylprop-2-en-1-aminium bromide 7.42 In a 5 mL
(C28), 132.56 (C6), 132.50 (C31), 131.92 (C26), 129.86 (C8), microwave vial equipped with a magnetic stir bar, compound 1
129.68 (C25), 129.45 (C30), 129.17 (C4), 128.69 (C9), 128.20 (0.355 g: 1.06 mmol) was dissolved in ACN (1 mL). Allyl bromide
(C29), 128.17 (C10), 123.17 (C5), 119.13 (C7), 115.30 (C3), 114.06 (0.09 mL, 1 mmol) was carefully added to the solution with a
(C24), 67.81 (C17), 64.65 (C15), 55.01 (C22), 50.77 (C16), 45.38 syringe and the reaction vessel was slightly heated, using a heat
(C1), 39.20 (C13), 33.76 (C21), 32.59 (C19), 28.70 (C20), 27.78 gun, to allow the reactants to fully dissolve. The capped vial was
(C18), 25.42 (C14) ppm. HRMS-ESI-TOF (m/z): [M+ ꢀ Brꢀ] then placed in the microwave and, with constant stirring, run at
calculated for C36H46BrN3O4S, 616.3224; found, 616.3203.
150 ꢃC for 2 min. To the resulting yellow mixture was added
6-(4-Benzoylphenoxy)-N-(3-(5-(dimethylamino)naphthalene- Et2O (ꢄ10 mL) and the vial placed in the refrigerator overnight.
1-sulfonamido)propyl)-N,N-dimethylhexan-1-ammonium chlo- The excess solvent was decanted out of the vial and a yellow
ride 6g.37 To a stirred solution of compound 1 (0.291 g: 0.870 precipitate layer attached to the bottom of the vial remained.
mmol) and 4-(6-chlorohexoxy)benzophenone (0.250 g: 0.790 The vial was then attached to a high-vacuum pump for 1 h to
mmol) were dissolved in ACN (2 mL) and le to stir in a 100 ꢃC remove any remaining solvent. A yellow coloured oil was
sand bath for 24 h. The resultant residue was precipitated using recovered and the crude product recrystallized in minimal
cold Et2O (4 mL) to afford the desired product 6g as a yellow amount of MeOH (2 mL). Aer 48 h, yellow solid crystals suit-
coloured powder. Yield: 0.435 g (84.5%). Mp ¼ 65–67 ꢃC. 1H able for X-ray crystallography were obtained. Yield: 0.36 g (75%).
NMR (400 MHz, CDCl3, d): 8.50 (d, 1H, J ¼ 8.5 Hz: H5), 8.28 (d, Mp ¼ 164–166 ꢃC; Rf ¼ 0.38 (5%, NH4OH–acetone). UV-Vis
1H, J ¼ 8.7 Hz: H10), 8.22–8.20 (m, 1H: H8), 7.80–7.71 (m, 5H: (MeOH, 1 ꢁ 10ꢀ3 M), lAbs max ¼ 339 nm, 3 ¼ 413 Mꢀ1 cmꢀ1, 3 ¼
H31, H25, H12, H9), 7.60–7.42 (m, 5H: H30, H29, H4), 7.15 (d, 560 Mꢀ1 cmꢀ1. 1H NMR (CD3OD, 400 MHz) d 8.58 (d, 1H, J ¼ 8.5
1H, J ¼ 7.5 Hz: H3), 6.93 (d, 2H, J ¼ 8.8 Hz: H24), 4.03 (t, 2H, J ¼ Hz: H9), 8.35 (d, 1H, J ¼ 8.4 Hz: H6), 8.23 (d, 1H, J ¼ 8.5 Hz:
6.4 Hz: H22), 3.54 (t, 2H, J ¼ 6.6 Hz: H15), 3.30–3.26 (m, 2H: H11), 7.66–7.59 (m, 4H: H5, H10), 7.30 (d, 1H, J ¼ 7.4 Hz: H4),
H17), 3.10 (s, 6H: H16), 3.08–3.06 (m, 2H: H13), 2.87 (s, 6H: H1), 5.96–5.86 (m, 1H: H18), 5.67–5.63 (m, 2H: H19), 3.83 (d, 2H, J ¼
1.84–1.78 (m, 6H: H21, H18, H14), 1.55–1.25 (m, 4H: H20, H19) 7.35 Hz: H17), 3.21–3.17 (m, 2H: H15), 2.97 (t, 2H, J ¼ 6.09 Hz:
This journal is © The Royal Society of Chemistry 2014
J. Mater. Chem. B, 2014, 2, 1509–1520 | 1515

View Article Online
Journal of Materials Chemistry B
Paper
H13), 2.90 (s, 6H: H16), 2.88 (s, 6H: H1), 1.89–1.84 (m, 2H: H14)
ppm; 13C{1H} NMR (CD3OD, 100.6 MHz) d 151.94 (C2), 135.17
(C11), 130.08 (C8), 129.76 (C7), 129.37 (C9), 129.17 (C10), 128.31
(C6), 128.15 (C19), 124.54 (C18), 123.20 (C4), 118.94 (C5), 115.25
(C3), 66.23 (C17), 61.50 (C15), 47.42 (C16), 44.44 13 (C1), 39.26
(C13), 22.66 (C14) ppm. HRMS (ESI-TOF) (m/z): [M+ ꢀ Brꢀ]
calculated for C20H30BrN3O2S: 376.2057; found 376.2053.
Results and discussion
Synthesis and characterization
Quaternary ammonium dansyl uorescent tags were synthe-
sized by a Menshutkin reaction between the dansyl amine
precursor 1 (Scheme 1) and various linkers (Scheme 2).
Compound 1 was obtained in high yield (97%) by a modied
procedure from literature and puried by avoiding both a
problematic acid–base extraction and column chromatog-
raphy.41 Previous preparations of 1 had called for quenching of
the reaction with phosphate buffer and or sequential acidifying/
basifying steps followed by extraction into DCM, which in our
hands lead to inseparable emulsions and low yields. A more
direct work up included the initial acidication of the reaction,
removal of the DCM, followed by the addition of base (6 N KOH
in brine at ꢀ20 ꢃC, O/N) and nally precipitation of the desired
compound. Precursor 1 was isolated by vacuum ltration,
washed (4 ꢁ 50 mL) with cold H2O and recrystallized from 20%
(v/v) EtOH–H2O to afford X-ray quality crystals. Compound 1 can
be readily scaled up (25 g) and used in the preparation of new
dansyl QAC's (Scheme 2) displaying a variety of functional
linkers for graing onto porous and non-porous surfaces.
All quaternization reactions were performed in sealed glass
vials with reuxing acetonitrile (ACN) for 7–48 h depending on
the alkyl halide. Reaction completion, monitored by NMR (1H:
CDCl3) for products 2–7, revealed the characteristic disappear-
ance of the dimethylamino protons at ꢄ2.2 ppm of 1 and the
appearance of two new upeld resonances at ꢄ3.5 ppm [(–CH2–
N+(Me2)–CH2–)] and at ꢄ3.3 ppm [–N+–(CH3)2] (Fig. 2). The
phosphorus containing compounds, 3a–b, prepared from
precursors possessing a bromo leaving group formed within 7
h, while the chloro-containing silane (2) and thioacetate (5)
compounds prepared from precursors with chloro leaving
groups required substantially longer reaction times (24–48 h). A
simple and convenient purication method was developed
based on the insolubility in Et2O of the newly formed QACs.
Compounds 2–7 precipitated directly from solutions using cold
Et2O. They are initially isolated as viscous oils attached to
the walls of the vial aer several cycles of rinsing and
Scheme 2 Preparation of fluorescent anchors for binding to porous
and non-porous surfaces.
Fig. 2 1H NMR spectra overlay of compounds 1 (CDCl3), 3a (CDCl3)
and 3c (D2O).
decantation. Further drying under reduced pressure resulted in
the isolation of light yellow uorescent powders in modest to
good yield (35–94%) and high purity. The quaternization
Scheme 1 Preparation of the precursor dansyl amine 1.
1516 | J. Mater. Chem. B, 2014, 2, 1509–1520
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
Journal of Materials Chemistry B
reaction for the silane derivative 2 showed, along with the two their expected structures; with the 13C NMR spectra revealing
new upeld proton resonances, a 29Si{1H} NMR (CD3OD) reso- the expected ketone carbon resonance at dC z 195 ppm with the
nance at d ¼ ꢀ68.4 ppm.
aromatic carbon bound to oxygen shied slightly upeld at dC
The dansyl phosphonate QAC's, 3a and 3b, were twice de- z 162 and 152 ppm. Compound 1, allyl bromide, and ACN were
alkylated to the corresponding phosphonic acid 3c by reuxing combined in a reaction vessel and stirred with microwave
ꢃ
in mineral acids (Scheme 3). As expected, faster de-alkylation heating at 150 C for 2 min. The reaction was cooled, ltered
was accomplished with HBr when compared to HCl, and with and compound 7 recovered as an oily, yellow coloured semi-
the i-PrO leaving group versus that of the EtO group. It was also solid. Recrystallization in a minimal amount of MeOH provided
necessary to use aqueous HBr as anhydrous HBr (20% in EtOH) yellow crystals in good yield (75%). Analysis of 7 by NMR
was signicantly slower at cleaving the phosphonate ester and (CD3OD) revealed characteristic vinyl hydrogen (dH ¼ 5.89 and
could not be forced to reach completion even aer prolonged dH ¼ 5.64 ppm) and carbon (dC ¼ 128.15 and dC ¼ 124.54 ppm)
heating. In aqueous HBr, the reaction with 3a or 3b was resonances. With the exception of 6 and 7, all dansyl QAC
complete aer 1–2 h, whereas aer 48 h of heating 3a in etha- derivatives with an electronegative atom present in the linker
nolic HBr, the reaction was only 71% complete by NMR. The (i.e. 2, 3a, 3b, 3c, 4, 5) are H2O soluble. Compounds 6a–h and 7,
NMR (1H, 31P{1H}: CDCl3) spectrum for the diphosphonate bearing the hydrophobic benzophenone and/or allyl group are
esters 3a and 3b (31P NMR, dP ¼ 29.29 and dP ¼ 27.32 ppm only slightly soluble in H2O, but readily dissolved in EtOH.
respectively) showed a slight upeld shi in 31P resonance to
20.99 ppm (D2O) and the disappearance of the hydrogen reso-
X-ray crystallography of 1 and 7
nances of the Et (dH ¼ 4.06, 1.28 ppm) and i-Pr groups (dH
¼
4.69, 1.26 ppm) aer ester hydrolysis to the free phosphonic
acid 3c (Fig. 2). Dansyl a-bisphosphonate, 4, was also synthe-
sized from 1 and 3-iodopropyl-a-bisphosphonate with NMR
(CDCl3) analysis showing the expected hydrogen (dH ¼ 3.06
ppm), carbon (dC ¼ 50.49 ppm) and phosphorus (dP ¼ 24.42
ppm) resonances characteristic of the aminophosphonate
group. However, no dealkylation of 4 to the free phosphonic
acid was investigated.
The thioacetate protected dansyl derivative, 5, selected for
potential binding onto noble metals, was also successfully
prepared from 1 and commercially available 3-chloropropylth-
ioacetate. NMR analysis (1H, 13C: CDCl3) of 5 revealed charac-
Schematic representations of a unit cell molecule of precursor
dansyl compound 1 and the ammonium dansyl allyl salt 7 are
depicted in Fig. 3. Crude 1 was re-crystallized using a 20% (v/v)
EtOH–H2O mixture, resulting in the isolation of ne, clear
prismatic crystals. Crystal structure analysis of 7 reveals C–N
43
˚
bond lengths typical for an ammonium salt (ꢄ1.50 A).
UV-Vis and uorescence spectroscopy
As expected, all dansyl QAC derivatives analysed in MeOH
exhibit nearly identical absorption spectra (lAbs max ¼ 340 nm,
Fig. 4) and uorescence emission spectra (lEm max ¼ 516 nm,
Fig. 5) characteristic of the green-yellow dansyl tag.35 Only
compound 6a exhibited a major absorption wavelength outside
typical values with lAbs max centered closer to ꢄ300 nm. This is
likely the result of strong p–p* absorption of the benzophenone
group. In aqueous environments at low pH (0.1 N HCl), uo-
rescence quenching of the dansyl uorophore 2 was observed
likely due to protonation of the aromatic N,N-dimethylamine
moiety (see ESI, Fig. S84†). At pH 7 (phosphate buffer), no
quenching was observed and a characteristic dansyl uores-
cence spectra, similar to the uorescence in MeOH solutions,
was observed. At high pH (0.1 N NaOH), the absorption was
shied to ꢄ310 nm resulting in a lower intensity emission at
516 nm when excited at 340 nm (see ESI, Fig. S83 and S84†).
teristic acetate hydrogen (dH
¼
2.28 ppm) and carbon
resonances (dC ¼ 195.80 and dC ¼ 30.77 ppm). However, an
attempted deprotection of 5 to the free thiol (MeOH–KOH) was
unsuccessful with the reaction mixture changing colour from a
light yellow to green and nally to a deep purple colour. This is
likely due to decomposition of the free thiol. No further
attempts to make the free thiol derivative were carried out.
A series of benzophenone terminated quaternary ammo-
nium materials, with different counter ions and alkyl chains,
were prepared from the reaction of 1 with the appropriate
ꢃ
(n-haloalkoxy)benzophenone derivative (100 C for 24 h). NMR
analysis (1H, 13C{1H}: CDCl3) of compounds 6a–h conrmed
Scheme 3 Cleavage of dansyl phosphonate and attempted cleavage
of the dansyl thioacetate.
Fig. 3 ORTEP representations of the unit cell components of 1 and 7.
J. Mater. Chem. B, 2014, 2, 1509–1520 | 1517
This journal is © The Royal Society of Chemistry 2014

View Article Online
Journal of Materials Chemistry B
Paper
Fig. 4 Absorption spectra of compounds 1–7 in MeOH (lAbs max ¼ 340
nm).
Fig. 6 Mechanism of grafting (a) silanes on polyhydroxy surfaces; (b)
phosphonic acids on metal oxide surfaces; (c) benzophenone and (d)
allyl groups onto plastic (C–H) surfaces.
Fig. 5 Fluorescence spectra of compounds 1–7 in MeOH (lEm max
516 nm).
¼
Coating experiments and the graing mechanism
Functional quaternary ammonium dansyl uorescent tags
attach to selective porous and non-porous surfaces via a self-
assembly process. Upon application, either by dip or spray
coating, anchors from the reactive dansyl molecule presumably
form bonds with complementary functional groups on the
substrate surface, thereby immobilizing an assumed monolayer
of the compound on the surface. Both silane, 2, and phosphonic
acid, 3c, dansyl compounds can form monolayers on –OH and
Fig. 7 Coating procedure of dansyl QAC tags onto porous and non-
porous surfaces.
metal oxides surfaces respectively aer a thermal curing step. In (w/v) H2O or MeOH solution of 2 or 3c followed by heating (80 ꢃC,
the process, H2O is eliminated as the by-product resulting in M– 5 min) and drying. Graing of 6a or 7 onto polypropylene (PP)
O–Si or M–O–P (where M ¼ titanium, stainless steel) to the and silicone was performed by rst pre-cleaning of all plastic
surface. If improperly cured, the monolayer may easily become samples (3.5 ꢁ 2.5 cm rectangles) by rinsing in distilled H2O,
displaced with a rinsing step because it is non-covalently bound followed by immersion in a MeOH bath and nally air drying
to the surface. The benzophenone 6a–h and vinyl 7 dansyl prior to use. The clean substrates were then dipped into a 0.01%
compounds require UV light to initiate binding (Fig. 6c and d). (w/v) EtOH solution of 6 or 7 and irradiated with UV for 2.5 min.
Excitation by UV can create radicals within the compounds and/ Any unbound material was then rinsed off from substrates using
or at the substrate surface that facilitate graing.
distilled H2O prior to visualization with UV light.
Fluorescent coatings (Fig. 7) of 2 on to cotton and silica
The dansyl uorescent coatings 2, 3c, and 6a were evaluated
nanoparticles (NP's) and 3c on to stainless steel were prepared on a number of porous and non-porous surfaces (Fig. 8). All
by dip coating or immersion of pre-cleaned samples in 0.01% uorescent coatings adhered to the surfaces without leaching,
1518 | J. Mater. Chem. B, 2014, 2, 1509–1520
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
Journal of Materials Chemistry B
ARC), and our supportive partners Bioshield Technologies
Canada, Ltd, and Pureshield. We are also grateful for the
editorial help by Robert Gossage and Russell Viirre.
References
1 L. Ferreira and A. Zumbuehl, J. Mater. Chem., 2009, 19, 7796–
7806.
2 D. Campoccia, L. Montanaro, P. Speziale and C. R. Arciola,
Biomaterials, 2010, 31, 6363–6377.
3 S. L. Warnes, C. J. Highmore and C. W. Keevil, mBio, 2012, 3,
e00489.
4 D. Lebeaux, A. Chauhan, O. Rendueles and C. Beloin,
Pathogens, 2013, 2, 288–356.
5 K. Page, M. Wilson and I. P. Parkin, J. Mater. Chem., 2009, 19,
3819–3831.
6 J. C. Tiller, C.-J. Liao, K. Lewis and A. M. Klibanov, Proc. Natl.
Acad. Sci. U. S. A., 2001, 98, 5981–5985.
7 A. M. Klibanov, J. Mater. Chem., 2007, 17, 2479–2482.
8 A. J. Isquith, E. A. Abbott and P. A. Walters, Appl. Microbiol.,
1972, 24, 859–863.
9 J. Amalric, P. H. Mutin, G. Guerrero, A. Ponche, A. Sotto and
J.-P. Lavigne, J. Mater. Chem., 2009, 19, 141–149.
10 P. Thebault, E. Taffin de Givenchy, R. Levy, Y. Vandenberghe,
Fig. 8 Images of (A) medical grade silicone tubing coated with 6a
under UV light (control to the left), (B) silica NP's with control left and
treated with 2 right, (C) polypropylene sample UV coated with 6a and
stained with bromophenol blue, (D) polypropylene UV coated with 6a
under UV light, (E) stainless steel control top and a 3c coated sample
bottom under visible light and (F) under UV light.
´
F. Guittard and S. Geribaldi, Eur. J. Med. Chem., 2009, 44,
4227–4234.
11 P. E. Thebault, R. Taffin de Givenchy, Y. Levy,
´
F. Vandenberghe, F. Guittard and S. Geribaldi, Eur. J. Med.
Chem., 2009, 44, 717–724.
12 P. H. Mutin, J. Amalric, G. Guerrero, A. Ponche and
J.-P. Lavigne, Eur. Cells Mater., 2011, 21, 63.
13 J. C. Tiller, Antimicrobial Surfaces, Bioactive Surfaces,
Advances in Polymer Science, Springer, Berlin/Heidelberg,
2011, pp. 1–25.
14 V. P. Dhende, S. Samanta, D. M. Jones, I. R. Hardin and
J. Locklin, ACS Appl. Mater. Interfaces, 2011, 3, 2830–2837.
15 H. Han, J. Wu, C. W. Avery, M. Mizutani, X. Jiang,
M. Kamigaito, Z. Chen, C. Xi and K. Kuroda, Langmuir,
2011, 27, 4010–4019.
16 F. Costa, I. F. Carvalho, R. C. Montelaro, P. Gomes and
M. C. L. Martins, Acta Biomater., 2011, 7(4), 1431–1440.
17 A. D. Fuchs and J. C. Tiller, Angew. Chem., Int. Ed., 2006, 45,
6759–6762.
18 H. Murata, R. R. Koepsel, K. Matyjaszewski and A. J. Russell,
Biomaterials, 2007, 28, 4870–4879.
19 K. Lewis and A. M. Klibanov, Trends Biotechnol., 2005, 23,
343–348.
20 Z. Li, D. Lee, X. Sheng, R. E. Cohen and M. F. Rubner,
Langmuir, 2006, 22, 9820–9823.
21 C. J. Ioannou, G. W. Hanlon and S. P. Denyer, Antimicrob.
Agents Chemother., 2007, 51, 296–306.
22 M. Diz, A. Manresa, A. Pinazo, P. Erra and M. R. Infante, J.
Chem. Soc., Perkin Trans. 2, 1994, 8, 1871–1876.
23 K. J. Stanger, J.-J. Lee and B. D. Smith, J. Org. Chem., 2007, 72,
9663–9668.
as evident by the evaluation of the washings for uorescence
active residue.
Conclusions
Novel dansyl-functionalized QAC's bearing various chemical
anchors specic for graing onto porous and non-porous
surfaces were successfully prepared via a Menshutkin reaction
with the dansyl amine, 1. Compounds 2–7 were readily puried
by trituration with Et2O without resorting to column chroma-
tography and fully characterized by NMR (1H, 13C, 29Si (2), 31P
(3a–c, 4)), HRMS, UV-Vis and uorescence spectroscopy. X-ray
crystal structures were obtained for uorophores (1, 7). The
dansyl-silane 2 was prepared on a large scale and graed onto
textiles and silica NP's. Dansyl phosphonic acid 3c was
successfully graed to stainless steel coupons, while the dansyl
QAC 6a containing the benzophenone photoactive crosslinker
was used to coat plastic surfaces (PP, silicone). The inclusion of
a trace amount of covalently bound dansyl molecules to
surfaces treated with an antimicrobial QAC coating is expected
to provide a simple and useful way of determining product
identity and coverage quality.
Acknowledgements
The authors are grateful for the nancial support from the 24 J. D. Reinheimer, J. D. Harley and W. W. Meyers, J. Org.
Applied Research and Commercialization Initiative (FED-DEV
Chem., 1963, 28, 1575–1579.
This journal is © The Royal Society of Chemistry 2014
J. Mater. Chem. B, 2014, 2, 1509–1520 | 1519

View Article Online
Journal of Materials Chemistry B
Paper
25 N. Menshutkin, Ann. Chem. Pharm., 1865, 133, 317–320.
26 M. Andresen, P. Stenstad, T. Møretrø, S. Langsrud,
36 H. R. Kricheldorf and R. Burger, Makromol. Chem., 1993, 194,
1197–1207.
K.
Syverud,
L.-S.
Johansson
and
P.
Stenius, 37 A. Mocella, UV Cured Benzophenone Terminated
Quaternary Ammonium Antimicrobials for Plastics, BSc
Biomacromolecules, 2007, 8, 2149–2155.
27 H. Nikawa, K. Ishida, T. Hamada, T. Satoda, T. Murayama,
thesis, Ryerson University, April 2011.
T. Takemoto, M. Tamamoto, H. Tajima, S. Shimoe and 38 M. F. Saettone, C. Alderigi, B. Giannaccini, C. Anselmi,
H. Fujimoto, Dent. Mater. J., 2005, 24, 570–582.
28 S. M. Abou El Ola, R. Kotek, W. C. White, J. A. Reeve,
P. Hauser and J. H. Kim, Polymer, 2004, 45, 3215–3225.
29 R. R. Egan, J. Am. Oil Chem. Soc., 1978, 55, 118–121.
30 Y. H. Li, L. M. Chan, L. Tyler, R. T. Moody, C. M. Himel and
D. M. Hercules, J. Am. Chem. Soc., 1975, 97, 3118–3126.
31 V. Tharmaraj and K. Pitchumani, J. Mater. Chem. B, 2013, 1,
1962–1967.
M. G. Rossetti, M. Scotton and R. Cerini, Int. J. Cosmet.
Sci., 1988, 10, 99–109.
39 R. Acosta, M. Garcia, A. Rosales, C. Gonzalez, L. Berlanga,
G. Arias and N. S. Allen, Polym. Degrad. Stab., 1996, 52, 11–
17.
40 K. Mistry, New Self-assembling Quaternary Ammonium
Fluorescent Compounds, BSc thesis, Ryerson University,
April 2011.
32 L. Ding and Y. Fang, Chem. Soc. Rev., 2010, 39, 4258–4273.
33 L. Mu, W. Shi, G. She, J. C. Chang and S.-T. Lee, Angew.
Chem., Int. Ed., 2009, 48, 3469–3472.
34 B. Alkhouri, R. A. Denning, P. K. Chiaw, P. D. W. Eckford,
W. Yu, C. Li, J. J. Bogojeski, C. E. Bear and R. D. Viirre, J.
Med. Chem., 2011, 54, 8693–8701.
41 X. Wang and H. Schneider, J. Chem. Soc., Perkin Trans. 2,
1998, 6, 1323–1328.
42 H. Deng, Vinyl Terminated Quaternary Ammonium
Antimicrobials for Plastics and Metals, BSc thesis, Ryerson
University, April 2013.
43 F. H. Allen, O. Kennard, D. G. Watson, L. Brammer,
A. G. Orpen and R. Taylor, J. Chem. Soc., Perkin Trans. 2,
1897, 2, S1–S19.
35 S.-M. He, Y. Luo, B. Hove-Jensen and D. L. Zechel, Bioorg.
Med. Chem. Lett., 2009, 19, 5954–5957.
1520 | J. Mater. Chem. B, 2014, 2, 1509–1520
This journal is © The Royal Society of Chemistry 2014