Molecules 2021, 26, 1501
8 of 10
FeSO (0.36 mM) and ferrozine (40 mM). In all experiments, negative controls (blanks) and
4
colour controls (without chelating indicators) were performed. At least three independent
experiments (six replicates/each) were conducted, for each experimental condition.
3
.6. Software
Chemical structures were designed using ChemDraw Ultra 12.0. Graphics and sta-
tistical analysis were performed using Microsoft Excel and GraphPad Prism 7.0. Bruker
APEXIII [33] software package including SAINT V8.38A [34] and SADABS-2016/2 [35
]
was used for data reduction of the X-ray crystallography work. SHELXT-2014/5 [29] and
SHELXL-2018/3 [30] and PLATON (v. 2010420) [36] were used for the structure solution,
refinement and structure analysis and drawing of crystallographic figures, respectively.
4. Conclusions
In short, this work unveils a new compound derived from saccharin capable of
selectively chelating Cd(II), compared to Cu(II) and Fe(II). 3-((5-(trifluoromethyl)-1,3,4-
thiadiazol-2-yl)amino)benzo[d]isothiazole 1,1-dioxide (AL14) was analyzed in detail and its
1
13
structure confirmed by 1D NMR ( H and C), 2D NMR (TOCSY, HSQC, and HMBC), X-ray
+
crystallography, HRMS-ESI and UV-Vis. In these experiments, the maximum chelating
activity for Cd(II), 69.0
without previous contact time. The concentration of ligand capable of removing 50% of
Cd(II) concentration in solution (IC ) is 7.857 mM. Reduced or no activity for Cu(II) and
±
3.3%, was achieved for [AL14] = 20 mM and [Cd] = 9 mM,
50
Fe(II) was observed, respectively. These are the first studies revealing the potential of this
compound for selective Cd(II) chelation. Additional studies will be carried out, considering
other environmentally relevant metal ions to assess their possible interference with the
chelating capacity of this new and relatively low-cost ligand.
1
Supplementary Materials: Figure S1: H NMR spectra of 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-2-
1
3
yl)amino)benzo[d]isothiazole 1,1-dioxide (AL14) in DMSO-d , Figure S2: C NMR spectra of 3-((5-
6
(
trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]isothiazole 1,1-dioxide (AL14) in DMSO-d6,
Figure S3: TOCSY spectra of 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]isothiazole
,1-dioxide (AL14) in DMSO-d , Figure S4: HSQC spectra of 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-
1
6
2
-yl)amino)benzo[d]isothiazole 1,1-dioxide (AL14) in DMSO-d , Figure S5: HMBC spectra of 3-((5-
6
(trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]isothiazole 1,1-dioxide (AL14) in DMSO-d6,
Figure S6: HMBC (expanded) spectra of 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]
isothiazole 1,1-dioxide (AL14) in DMSO-d , Figure S7: Electrospray ionization mass spectrum
6
+
in positive-ion mode (HRMS-ESI ) of 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]
isothiazole 1,1-dioxide (AL14), X-ray crystallography data, detailed synthesis procedure, Scheme S1
:
Preparation of 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]isothiazole 1,1-dioxide
(AL14).
Author Contributions: Conceptualization, J.F.L., L.B. and M.L.S.C.; methodology, all authors; val-
idation, J.F.L., L.B., J.A.P. and M.L.S.C.; formal analysis, J.F.L. and L.B.; investigation, all authors;
resources, L.B., J.A.P. and M.L.S.C.; writing—original draft preparation, J.F.L., B.G. and P.S.M.A.;
writing—review and editing, J.F.L., L.B. and M.L.S.C.; visualization, J.F.L., P.S.M.A., J.A.P.; supervi-
sion, M.L.S.C.; project administration, J.F.L., A.L.F. and M.L.S.C.; funding acquisition, M.L.S.C. All
authors have read and agreed to the published version of the manuscript.
Funding: This study received Portuguese national funds from FCT—the Foundation for Science
and Technology, through projects UIDB/04326/2020 (CCMar) UIDB/04564/2020 (CFisUC) and
UIDP/04564/2020 (CFisUC), and from the operational programmes CRESC Algarve 2020 and COM-
PETE 2020 through project EMBRC.PT ALG-01-0145-FEDER-022121. J.F.L. and A.L.F. also acknowl-
edge CCMAR for fellowships. P.S.M.A thanks FCT for the doctoral grant SFRH/BD/130407/2017.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: A CIF file containing supplementary crystallographic data was de-
posited at the Cambridge Crystallographic Data Centre with reference CCDC 2063726.