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Molecular design and QSAR study of low acute toxicity biocides with 4,4′-dimorpholyl-methane core obtained by microwave-assisted synthesisCCDC reference numbers 750435-750438. For crystallographic data in CIF or other electronic format see DOI: 10.1039/b905153h
The solventless microwave-assisted synthesis of aldehydes ( 1a , 2b-h ) and morpholine ( 3 ) in 1 : 2 (aldehyde : morpholine) ratio yielded eight 4,4′-dimorpholyl-methanes ( 4a-4h ), which were thoroughly characterized through FT-IR, 1 H, 13 C and 2D NMR, confirming structures of type 4 . The descri...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Online Access: | Get full text |
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| Summary: | The solventless microwave-assisted synthesis of aldehydes (
1a
,
2b-h
) and morpholine (
3
) in 1 : 2 (aldehyde : morpholine) ratio yielded eight 4,4′-dimorpholyl-methanes (
4a-4h
), which were thoroughly characterized through FT-IR,
1
H,
13
C and 2D NMR, confirming structures of type
4
. The described compounds are dimorpholino-methane (
4a
), 2-(dimorpholinomethyl)-phenol (
4b
), 4-bromo-2-(dimorpholinomethyl)-phenol (
4c
), 2,4-di-
tert
-butyl-6-(dimorpholinomethyl)-phenol (
4d
), 4,4′-(pyridin-2-ylmethylene)-dimorpholine (
4e
), 4,4′-((4-
iso
-propylphenyl)methylene)-dimorpholine (
4f
), 4,4′-(naphthalen-1-ylmethylene)-dimorpholine (
4g
) and 4,4′-(pyren-1-ylmethylene)-dimorpholine (
4h
). Additionally, single crystal X-ray diffraction analysis for
4b
,
4c
,
4d
and
4e
derivatives was accomplished showing interesting geometrical features. The obtained 4,4′-dimorpholyl-methanes were subjected for two biological tests, (i) acute toxicity, related to
Photobacterium phosphoreum
(
Vibrio fischeri
), and (ii) biocidal activities, determined for
B. subtilis
,
E. coli
and
Ps. fluorescence
strains. The results show that
4a-h
compounds have varying degrees of toxicity, classified as
4a
,
4b
,
4c
,
4e
and
4f
as slightly to moderately toxic agents,
4g
and
4h
as highly toxic chemicals, and
4d
as an extremely toxic compound. Besides, the biocidal activities, which is controlled mainly by the substituent directly bonded to the methinic bridge (named C5, which originally is the carbon atom of the aldehyde functionality), have shown varying degrees of inhibitory effects on the growth of selected strains, depending on the chemical structure of
4a-h
. A QSAR study was developed, and quantum-chemical parameters of
4a-h
were obtained with the DFT approach at the B3LYP/6-311G(d) level of theory in the gas phase. Hence ten molecular descriptors were determined, being
E
HOMO
,
E
LUMO
, GAP, C5 Mulliken atomic charge (AC
Mulliken
), C5 atomic charge of NBO (AC
NBO
), dipolar moment (
μ
), molecular hydrophobicity as log
P
, molecular volume (Vol), electrostatic potential (ESP) and δ
13
C(C5), all of them being typical determinants of biological activities in other, different or related, molecular systems. A linear combination from three to six molecular descriptors was chosen as a multivariate model to achieve correlations in order to relate them to their acute toxicity and understand the obtained trend. Three sets of descriptors accomplished the statistical goal, and through a |
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| ISSN: | 1463-9262 1463-9270 |
| DOI: | 10.1039/b905153h |