945

* For correspondence.

Oxidation Communications 35, No 4, 945–961 (2012)

Biological systems – QSPR/QSAR analysis

BIOACTIVE NITROGEN-CONTAINING COMPOUNDS WITH

SPATIAL CARBOCYCLIC GROUPS: SYNTHESIS, MODELLING

OF PHYSICAL PROPERTIES AND USE

N. LEKISHVILIa*, KH. BARBAKADZEa, D. ZURABISHVILIa,

G. LEKISHVILIb, B. ARZIANIb, K. GIORGADZEa, A. FAINLEIBc,

O. GRIGORIEVAc, W. BROSTOWd

aFaculty of Exact and Natural Sciences, Institute of Inorganic–Organic Hybrid

Compounds and Non-traditional Materials, ‘Ivane Javakhishvili’ Tbilisi State

University, 0179 Tbilisi, Georgia

E-mail: nodar@lekishvili.info bTbilisi State Medical University, Tbilisi, Georgia

E-mail: gleki@gmail.com cInstitute of Macromolecular Chemistry, National Academy of Sciences of Ukraine,

Kiev, Ukraine

E-mail: fainleib@i.kiev.ua dLaboratory of Advanced Polymers & Optimised Materials (LAPOM), Department

of Materials Science and Engineering, University of North Texas, 1150 Union

Circle No 305310, Denton, TX 76203-5017, USA

E-mail: wbrostow@yahoo.com

ABSTRACT

Quantitative ‘struc ture–pro per ties’ relation ships (QSPR/QSAR) based on experimental

data for construction of models of depen den ces of physical properties of bioactive

nitrogen-containing compounds with bioactive spatial carbocyclic groups on mole-

cu lar structures have been studied. Several sets of molecular descriptors have been

used. Presence of the data set outliers was con trolled by using PCA; to ascertain the

quality of models cross-validation has been used. Virtual bio screening and activity

towards various micro organisms of the obtained com pounds have been established.

,QRUJDQLF�RUJDQLF�K\EULG�PDWHULDOV�ZLWK�VSHFL¿F�SURSHUWLHV�EDVHG�RQ�RUJD�QLF�KHWHUR�chain polymers and coordination compounds of some transition metals and bioactive

nitrogen-containing compounds have been obtained and studied. Tri bo lo gical prop-

erties and stability towards various factors (stability towards O2, CO

2 and moisture

complex action); photochemical stability (stability towards ultraviolet and visible

946

light) and isothermal ageing of the created com po site materials have been studied.

By preliminary investigations it was established that the created bioactive composites

could be used for prevention of materials from bio-dete rioration and non-controlled

biodegradation, inhibition of growth and expansion of micro organisms, which are

causal factors of infectious diseases and for prophylaxis and treatment of the above-

mentioned diseases.

Keywords: QSPR/QSAR, models, descriptor, calculation, bioactive, bioscreening,

anti biocorrosive, tribology, composite.

AIMS AND BACKGROUND

Biodegradation of synthetic and natural materials by various microorganisms affects

a wide range of industries and techniques. In accordance with the existed statisti-

cal data more than several hundred kinds of such aggressive microorganisms are

known1–3, which damage especially carbon-containing polymers and materials. The

DFWLRQV�RI�PLFUR�RUJDQLVPV�RQ�SRO\PHUV�DUH�LQÀXHQFHG�E\���GLIIHUHQW�SURFHVVHV���D��deterioration and degradation of polymers, which serve as a native sub stance for

JURZWK�RI� WKH�PLFUR�RUJDQLVPV��GLUHFW�DFWLRQ��� �E�� LQÀXHQFH�RI�PHWDEROLF�SURGXFWV�of the micro organisms (indirect action). Losses caused by destruction of natural and

synthetic materials with micromycets reach enormous amounts and constitute annu-

ally milliards of dollars4,5.

Historical buildings, archeological artifacts (made of metals and their alloys,

leather and/or wood), museum exhibits and collections of art work – all of them need

SURWHFWLRQ� IURP� LQÀXHQFH� RI� YDULRXV� DJJUHVVLYH�PLFURRUJDQLVPV��6R� WRJHWKHU� WKH�protection of cultural heritage and various syn thetic and natural materials is a global

problem and this topic is actual all over the world6.

One of the ways to protect the synthetic materials from the action of micro o r-

ganisms is a creation of novel polymer coatings7�ZLWK�KLJK�ELRDFWLYLW\�E\�PRGL¿FD-tion of various poly functional adhesive polymer matrices with biologically active

compounds8. Therefore, synthesis of com pounds for bioactive composites and created

DQWLELRFRUURVLYH�FRDWLQJV�EDVHG�RQ�WKHP�IRU�YDULRXV�QDWXUDO��V\QWKHWLF�DQG�DUWL¿FLDO�PDWHULDOV�LV�H[WUHPHO\�VLJQL¿FDQW�DQG�UHTXLUHV�IXUWKHU�GHYHORSPHQWV9.

For the time being in the various spheres of science and technique is giving scien-

tist special attention to asymmetric carbocyclic compounds (such as adamantane and

LWV�GHULYDWLYHV���0RGL¿FDWLRQ�RI�WKH�YDULRXV�ELRDFWLYH�FRPSRXQGV�E\�LPPXQRWURSLF�and membranotropic adamantane group has a great potential because of impro ve ment

of their hydrolytic stability and increasing their biological activity10–13.

947

EXPERIMENTAL

Nitrogen-containing compounds with spatial (adamantane) carbocyclic groups and

adamantane-containing hydrazide coordination compounds of tran si tion metals were

synthesised by us earlier14.

Polyester urethane (PU). (1) Mixture of 50 g (0.1 mol) polyoxypropylenglycole, 2.6

g (0.05 mol) diethylenglicole and 26.1 g (0.3 mol) toluylendiisocyanate (the mixture

of 2,4- and 2,6-iso me res with ratio 65:35 wt. %) was stirred for 1 h at 80–90oC until

formation of hexa methy len di iso cya nate. The monitoring of the reaction was carried

out by following the content of NCO-group (the optimum content of the NCO-group

for the above-mentioned polyester urethane is ~7.6%); (2) To hexamethylendiisocy-

anate 0.05 mol hydrazine hydrate (the 1% solution of hydrazine hyd ra te in dimethyl

formamide) with the purpose of chain lengthening was added. The mixture was stirred

for 24 h. The monitoring of the reaction was carried out by the method of infrared

spectro sco py, in particular, by following the disappearance of the characteristic ab-

sorption bands of NCO-group in the IR spec t ra of the research sample (2273 cm–1).

It was established that for polyester urethane Mw §��������

Sulphur-containing polyester urethane (PUS). For fuctionalisation of hexamethylen-

di iso cya nate was carried its sulphurisation with 98% sulphuric acid (5 wt.% of

hexamethylen di iso cya nate). To the mixture was added drop wise sulphuric acid for

20 min to 6.5–6.8% content of NCO-group. The reaction was carried under stirring

condition at 80–90oC for 5 h. The degree of sulphu risation of the obtained polyester

urethane was ~3 wt.% (the degree of sulphu risation was determined by titration of

sulpho-groups). It was established that for sulphur-containing polyester urethane Mw

§��������

Ionomer of sulphur-containing polyester urethane (PUSI). The sulphurised

hexamethylen di iso cya nate (Mw §����������ZDV�FRROHG�WR���±��oC and then was car-

ried out the transfer of SO3H-group from acid to salt form by addition of equimolar

(in relation to sulphuric acid) triethylamine. To the obtained iono-containing hexa-

methylendiisocyanate with the purpose of chain lengthening were added 0.05 mol 1%

water-solution of hydrazine hydrate under stirring condition for 24 h.

The antibiocorrosive coatings were prepared by the following way: to the cyclohex-

DQRQH�VROXWLRQ�RI�SRO\PHULF�PDWUL[�JUDGXDOO\�ZDV�DGGHG�D�GH¿QLWH�TXDQWLW\�RI�PRGL¿HU�(3 wt. %) and bioactive coor dination compound (3–5 wt. %) under stirring condition

until formation of light-colour homo ge nous mass. Later, the obtained composition

was laid in the form of thin layer on the surface of the selec ted various materials

�ZRRG��SODVWLF��WHÀRQ��HWF���IRU�SURWHFWLRQ�DQG�ZDV�NHSW�RQ�DLU�IRU���±���K�DW�URRP�temperature. After hardening, there was produced homogenous, smooth, mecha nically

stable protective layer.

948

Methods of analysis. Standard methods for obtaining and purifying of bioactive

compounds were used.

Tribological pro per ties of the polymeric matrices have been determined using

a Spanish Nano vea pin-on-disk Tribo me ter (Micro Photonics Inc.), Micro-Scratch

Tester (MST) (CSM, Neuchatel, Switzer land) Nicon Eclipse ME 600 Microscope.

Standard microbiological methods for study of bac te ricidal and fungicidal properties

of the synthesised compounds were used.

RESULTS AND DISCUSSION

With the purpose to establish the correlation between structure of possible bioactive

com pound and some of its fundamental properties we synthesised and studied some

anilides and nitro anilides14 containing spatial carbocyclic groups (adamantane) with

various organic radicals in ben zene ring (Scheme 1, Table 1). In order to select these

compounds we considered the availability of their synthesis and possibility of their

perspective for wide commercialisation.

S c h e m e 1

Nitrogen-containing derivatives of adamantane

NHC(O)

1, 9–14

O

R

5� 5�

OH

C(O)NH X

15, 16

Br

Br

X = C6H

4 – absent (15), C6H4 (16)

2–8

NO2

NHC(O)O

R

5� 5�

5��

5��=Ad;

Table 1. Main structures of nitrogen-containing derivatives of adamantane

Compound* R 5� 5� Compound R 5� 5�1 H CH

3 Ad** 8 Cl 4-ClC

6H

4Ad

2 H CH3

Ad 9 H C2H

5Ad

3 H C2H

5Ad 10 H Ad CH

3

4 H Ad CH3

11 H Ad CH2C

6H

5

5 H Ad C6H

512 H Ad C

6H

5

6 H Ad CH2C

6H

513 H Ad Ad

7 H Ad Ad 14 Cl 4-ClC6H

4Ad

* Scheme 1; **�$G�±��GDPDQW\O�

The techniques of quantitative structure–property relationship (QSRR/QSAR) are used

for estab lishing reliable models of biological activities and physicochemical properties

of organic and ele ment-organic molecules. The afore-mentioned approach is based on

949

representation of molecular struc tures with numeric quantities. They are calculated

via straight forward algorithms and are known as molecular descriptors. Among the

latter, considerable attention is granted to the autocorrelation-based descriptors15.

Let us give a brief outline of the approach. Suppose s1, s

2, …, s

n are variables,

which present various molecular substructures. Most often, the paths of the corre-

sponding molecular graphs are considered. As is clear, n, i.e. the number of the paths

depends on the number of atoms, or, in the graph-theoretical context, on the number

of vertices. However, to build statistically reasonable models, one needs to represent

molecules with vectors (i.e. series of molecular descriptors) of the same length.

Therefore, we introduce a set of the template variables, t1, t

2, … t

m, where m remains

constant, i.e. is independent on the size of molecules of the dataset in question. The

afore-mentioned substructures are characterised by special functions. An example is

the product of numeric values of a physical property of the atoms of the substructure.

That is, if we consider only paths as substructures, we have:

f(si) = p

i0p

i1,

where p0 is a physical property of the origin of its path, and p1 – that of the terminal

vertex (atom) of the path. Examples of the physical property are sigma- and pi-charges,

electro-negativities, etc. Therefore, we arrive at a vector of the products of the physical

properties of the paths, f, which has dimensionality equal to n.

$XWRFRUUHODWLRQ�YHFWRUV�DUH�GH¿QHG�DV�OLQHDU�WUDQVIRUPV�RI�WKH�f vectors of the

dimen sio na lity n to the vectors a of the dimensionality m. The transform is given by

kernel matrix (K):

a = fK, or in the functional form: a(t�� ��K(t, s)f(s)ds.

The kernel matrix (K) has dimensionality (n, m). The vector a will always be of

size m, and therefore, independent on the size of the molecule. The kernels are given

via various functions. The kernel of 3D-MoRSE descriptor, for example, is given as

follows:

K(t, s) = sin t r(s)

,t r(s)

where r(s) is the Euclidean distance.

QSPR calculations. We used MDL Isis Draw 2.5.SP4 to build molecular models.

Afterwards, we concatenated the models into the dataset by use of EdiSDF 5.02. The

textual format of the dataset was SDF. We used VCC-Lab e-Dragon web application

for calculation of molecular descriptors. Statistic 6.0 was a tool of our choice for

building PCA and PLS models.

Among many available molecular descriptors at our disposal, we selected Radial

Distri bution Functions (RDF) (Ref. 16), Crystal Structure Codes (MoRSE) (Ref. 17),

WHIM (Ref. 18), GETAWAY (Ref. 19), and traditional topological indices20. Our data

set contained 16 compounds.

950

In order to detect outliers, i.e. the compounds, which did not belong to the mod-

elling population, we performed PCA (Ref. 21). However, unlike to our previous

contribution22, we did not identify any of the investigating compounds as outliers.

Fig. 1. Outlier detection by means of PCA. The descriptor used is GETAWAY

As one can see (Fig. 1), compounds 7, 8, 13–16 (Ref. 12) are situated some-

how farther than the main group. This alone does not allow for their removal. For

example, the Burden eigenvalues reveal that only compound 8 is an outlier (Fig.

2). When we used the Randic type invariants, none of the compounds left the main

group (Fig. 3). Therefore, we decided to keep all of the compounds in the training

dataset. It is noteworthy that the Randic type invariants clearly output several clusters

of compounds.

Fig. 2. Outlier detection by means of PCA. The descriptors used are the Burden eigenvalues

951

Fig. 3. Outlier detection by means of PCA. The descriptors used are the Randic type invariants

2XU�¿QDO� VWHS�ZDV� HVWDEOLVKPHQW� RI� UHODWLRQVKLSV� EHWZHHQ� WKHVH� GHVFULSWRUV�and the reten tions factors measured experimentally. Our studies show that the best

model was achieved by employing, again, the GETAWAY descriptors. We used PLS

(Ref. 23) as the number of predictors was much higher than that of cases. We used

FURVV�YDOLGDWLRQ�WR�GH¿QH�WKH�RSWLPXP�QXPEHU�RI�ODWHQW�YDULDEOHV��,Q�RXU�VWXG\��ZH�used 13 compounds in training set and 3 for the cross-vali da tion tests. Of course, the

prediction power was lower in case of cross-validation. We modelled both melting

points (m.p.) and retention factors (Rf) within the same model, which, therefore, had

2 responses.

The results of modelling look impressive as the square of the average correlation

FRHI¿FLHQW�ZDV�DV�KLJK�DV�������7KH�35(66�ZDV�DOVR�JRRG�HQRXJK��7DEOH�����2QH�FDQ�examine the experimental and calculated values (Table 3). A reader should take into

account that compounds 4, 13 and 16 produced the test (validation) set.

Table 2. Statistical parameters of the model

Latent

var.

No

Increase

R2 on Y

Average

R 2 on Y

Increase

R 2 on X

Average

R 2 on X

R 2 for

m.p.

R 2 for Rf

Sc. Press,

m.p.

Sc. Press,

Rf

Average

Sc. press

1 0.391833 0.391833 0.286528 0.286528 0.577891 0.205776 2.254355 1.727976 1.991166

2 0.286881 0.678714 0.275862 0.562390 0.611797 0.745632 2.094057 1.922039 2.008048

3 0.033169 0.711883 0.206076 0.768466 0.666069 0.757697 1.780881 1.833227 1.807054

4 0.041860 0.753743 0.109336 0.877802 0.670454 0.837033 1.763578 1.837925 1.800751

5 0.121957 0.875700 0.023599 0.901401 0.886302 0.865099 1.268438 1.445234 1.356836

6 0.028227 0.903927 0.048229 0.949629 0.910597 0.897258 1.211559 1.240578 1.226068

7 0.025273 0.929201 0.030173 0.979802 0.912324 0.946077 1.198989 1.180627 1.189808

8 0.023788 0.952989 0.004540 0.984342 0.939416 0.966562 1.389769 1.137673 1.263721

952

Table 3. Experimental versus calculated R/s

Compound m.p. (calc.) (oC) Rf (calc.) m.p. (exp.) (oC) R

f, (exp.)

1 184.9834 0.518455 178.5 0.60

2 126.5095 0.704182 134.5 0.65

3 142.8738 0.705937 134.5 0.73

4 102.3756 0.591046 121.5 0.42

5 154.5519 0.776873 152 0.80

6 128.6926 0.633454 128.5 0.65

7 171.7885 0.867685 173 0.86

8 167.9010 0.917788 169 0.91

9 193.2231 0.447994 206.5 0.40

10 166.1550 0.486902 166.5 0.50

11 178.3934 0.473237 160 0.41

12 170.2936 0.525245 181.5 0.53

13 198.3374 0.549713 240.5 0.77

14 175.8185 0.426382 176.5 0.45

15 226.3155 0.555867 226.5 0.55

16 183.8285 0.146642 194.5 0.17

Study of bioactive properties of adamantane-containing anilides and nitroanilides.

The modelling of the dependence of the structures of used nitrogen-containing ada-

mantane derivatives on their fundamental properties (m. p. and Rf) allows carrying

out the theoretical evaluation of possible bioactivity of same structures. We have

carried out the preliminary virtual bio screening of obtained compounds by using of

internet-system program PASS C&T (Ref. 24). The estimation of probable bioacti vity

of chosen com pounds was carried out via parameters Pa (active) and P

i (inactive);

when Pa>0.5, the compound also could be shown bioactive expe rimentally. Following

from the above-mentioned virtual bioscreening, based on the analysis of the obtained

results, the synthesised com pounds with experi men tally high probability (Table 4a)

(Pa>0.5) possibly will show the following bioactivity: anti bac terial, antibacterial

activity enhancer, antihel min tic, anti viral (Arbovirus,� ,QÀXHQ]D, Picorna virus), li-

pid metabolism regulator, urologic disorders treatment.

Herewith, in the halogenated nitrogen-containing adamantane (15 and 16) deriva-

tives increasing of antiviral (,QÀXHQ]D) activity were observed. The synthesised com-

pounds with experi men tally high probability (Table 4b) possibly will show the following

bioactivity: antiinfective, dopamine-release stimulant, antihelmintic, antiparasitic.

We have tested the bactericidal and fungicidal activity of synthesised com pounds

according to the method described in Ref. 25. To this target we have applied the test-

micro organisms – Pectobacterium aroideae, Fusarium arenaceum, Autinomyces gri-

seus and Fusarium proliferate. The test results showed that the synthesised compounds

have revealed selec ted bactericidal properties and have suppressed the development

RI�UHVHDUFK�FXOWXUHV��0LFUR�ELR�ORJLFDO�VWXG\�RI�WKH�LQYHVWLJDWHG�FRPSRXQGV�FRQ¿UPHG�the evaluated virtual concepts.

953

Tab

le 4

a. R

elat

ive

bio

acti

vit

y o

f so

me

nit

rogen

-conta

inin

g a

dam

anta

ne

der

ivat

ives

(1–1

4)

Com

-

pound

Pa

/Pi

lipid

met

abo-

lism

reg

ula

tor

5 h

ydro

xy-

trypta

min

e

rele

ase

in-

hib

itor

uro

logic

dis

-

ord

ers

trea

t-

men

t

anti

vir

al (

In-

ÀXHQ]D

)

anti

vir

al (

Pi-

corn

avi

rus)

anti

vir

al

(Arb

ovi

rus)

mem

bra

ne

in-

tegri

ty

agonis

t

dep

en-

den

ce t

reat

-

men

t

anti

bac

te-

rial

act

ivit

y

enhan

cer

1

–0.9

00/0

.004

0.8

72/0

.010

0.7

91/0

.004

0.7

05/

0.0

04

–0.7

03/0

.101

0.7

41/0

.014

–

2

–0.8

34/0

.004

0.8

13/0

.022

0.7

82/0

.004

0.6

73/0

.013

0.8

69/0

.003

–0.5

45/0

.056

0.4

36/0

.239

3

–0.8

23/0

.004

0.7

97/0

.027

0.8

16/0

.004

0.6

89/0

.010

0.8

99/0

.003

0.3

12/0

.170

0.3

89/0

.174

0.3

71/0

.311

5

–0.3

71/0

.087

–0.4

50/0

.052

0.5

72/0

.053

0.7

62/0

.010

0.5

48/0

.155

0.3

50/0

.218

0.5

50/0

.113

6

0.3

88/0

.213

0.2

56/0

.179

0.3

27/0

.315

0.2

69/0

.205

0.5

09/0

.097

0.6

13/0

.108

––

0.6

63/0

.022

7

0.3

44/0

.241

0.7

78/0

.005

0.7

45/0

.049

0.6

38/0

.011

0.6

79/0

.012

0.8

03/0

.005

–0.4

04/0

.160

0.4

98/0

.172

8

–0.7

46/0

.005

0.7

55/0

.044

0.5

49/0

.023

0.7

24/0

.005

0.8

20/0

.004

0.5

49/0

.154

0.5

43/0

.057

0.5

93/0

.070

9

– 0

.891/0

.004

0.8

55/0

.013

0.7

81/0

.004

––

0.7

52/0

.083

––

10

0.9

73/0

.003

––

––

–0.7

70/0

.075

––

110.9

66/0

.004

––

––

––

––

12

0.9

70/0

.003

––

––

–0.8

38/0

.043

––

13

0.9

71/0

.003

0.8

76 /

0.0

05

0.8

18/0

.021

0.7

75/0

.005

0.7

05/0

.004

––

––

14

–0.8

43/

0.0

05

0.7

88/0

.030

0.7

52/0

.005

––

0.7

92/0

.065

0.7

20/0

.017

–

Tab

le 4

b. R

elat

ive

bio

acti

vit

y o

f 1-(

N-3

,5-d

ibro

moben

zoyl)

amin

oad

aman

tane

(15)

and 4

/ -(1

-adam

anty

l)-2

-hydro

xy-3

,5-d

ibro

moben

zoyla

nil

ide

(16)

Com

-

pound

Pa/

Pi

anti

vir

al

(,QÀXHQ]D

)

anti

vir

al

(A

rbovi

rus)

anti

vir

al

(A

den

ovi

rus)

anti

vir

al

(P

icorn

avi

rus)

anti

infe

ctiv

e d

opam

ine-

re-

leas

e st

imula

nt

anti

hel

min

tic

(Nem

ato

des

)

anti

par

asit

ic

15

0.8

57/

0.0

03

–0.5

48/0

.005

–0.7

78/0

.005

0.8

48/0

.009

0.4

78/

0.0

57

0.4

22/0

.035

16

0.9

03/0

.002

0. 731/

0.0

20

0.6

17/0

.004

0.5

20/0

.088

0.8

07/

0.0

05

0.7

49/

0.0

29

0.5

44/

0.0

30

0.5

12/

0.0

17

954

,QRUJDQLF�RUJDQLF�K\EULG�PDWHULDOV�ZLWK�VSHFL¿F�SURSHUWLHV�EDVHG�RQ�WKH�V\QWKHVLVHG�

compounds. One of the modern ways to protect the synthetic and natural materials

from the action of micro organisms is a creation of novel antibiocorrosive coatings

with high bioactivity and multi-vectorial and directional action based on inorganic-

organic hybrid composites9. Anti bio corrosive coatings main ly contain 2 components –

biologically active compound and polymer matrix, where the bio acti ve compound is

dropped. Some polyfunctional hetero-chained organic polymers, such as poly ur etha ne

elastomers, polyurethane-acrylates, ionomers, etc. have been successfully used as a

matrix for creation of antibiocorrosive coatings. In this regard, special interest provoke

in many respects bioactive, including bactericide and fungicide poly urethanes26,27.

2Q�WKH�¿UVW�VWDJH�RI�WKH�UHVHDUFK�IRU�SUHSDUDWLRQ�RI�µVKRUW�WHUP¶�DFWLRQ�SRO\PHULF�composites were selected the following polyurethanes:

1. Polyester urethane (PU):

(OR)n OCNH

O

Ar NHC O5� NHNHCNH*

O

*2

OCNH

O

Ar NHC

O

*

O

Ar NHC

O

*3

,

where R = –CH2CH(CH

3�±��5�� �±�&+

2)

2O(CH

2)

2–.

2. Sulphur-containing polyester urethane (PUS):

(OR)n OCNH

O

Ar NHC O5� NHNHCNH*

O

*2

OCNH

O

Ar NHC

O

*

O

Ar NHC

O

*3

,

where Ar =

CH3

HO3S

;

CH3

SO3H

; R = –CH2CH(CH

3�±��5�� �±�&+

2)

2O(CH

2)

2–.

3. Ionomer of sulphur-containing polyester urethane (PUSI):

(OR)n OCNH

O

Ar NHC O5� NHNHCNH*

O

*2

OCNH

O

Ar NHC

O

*

O

Ar NHC

O

*3 ,

where Ar =

CH3

(C2H5)3HNO3S

;

CH3

SO3NH(C2H5)3

;

+ _ +_

R = –CH2CH(CH

3)–;

5�� �±�&+2)

2O(CH

2)

2–.

4. Polyester urethane ‘BUTYP T-261’ based on 4,4-dimethylmethanediisocianate

and oligo buthy le neglicoladipinate.

955

Some adverse effects, in particular, low scratch and wear resistance and environ-

mental degradation have hindered many important applications of polymers28,29. Thus,

IRU�SK\VLFDO�DQG�RU�FKHPLFDO�PRGL¿FDWLRQ�RI�WKH�DERYH�PHQWLRQHG�SRO\XUHWKDQHV�ZLWK�the purpose of improving of tribological properties were used silicon-organic oligom-

ers, which will be able to improve several properties of the initial polymer systems

including mechanical (elastic, adhesive strength) and thermo-physical (frost- and

thermal-resistant) and hydrophobicity:

(a) Bis(hydroxyalkyl)polydimethylsiloxane:

�E��.�&�GLK\GUR[\PHWK\OYLQ\OROLJRRUJDQRVLOR[DQH��

HO{[Si(CH3)

2O]

98.5[Si(CH

3)(CH=CH

2)O]

1.5}

xH,

where x = 3–5.

As bioactive compounds for antibiocorrosive coatings we used other nitrogen-

containing ada man tane derivatives14, 30–32 such as transition metals coordination com-

pounds of adamantane-1-carbo xy lic acid hydrazide synthesised by us14,30 considering

their stability and ability to form dipole-dipole and hydride bonds with the polymeric

matrix. It was expected that hydrazide metal complexes will show various applica-

WLRQV� LQ� WKH�¿HOGV� VXFK�DV� IXQJLFLGDO�� EDFWHULFLGDO�� DQWLSDUDVLWLF�� DQWLR[LGDWLYH� DQG�cytotoxic studies31,32.

The most probable structures of the obtained coordination compounds13 are given

below:

S c h e m e 2

Adamantane-containing hydrazide coordination compounds of some transition metals

NH

O

NH2

M O

HNH2N

. nH2OXm

M = Cu, Co, Ni; X = NO3–, CH

3COO–; m = 1, 2; n = 1, 2.

By using the obtained polymeric matrices and coordination compounds (3–5 wt.

%) new effective and stable inorganic-organic antibiocorrosive coatings have been

obtained (Table 5).

956

Table 5. Polymeric composites and antibiocorrosive coatings based on polyurethanes and coordination

compounds

1 Polyester urethane (PU)

2 Sulphur-containing polyester urethane (PUS)

3 Sulphur-containing polyester urethane (PUS)/

3% .�&�GLK\GUR[\PHWK\OYLQ\OROLJRRUJDQRVLOR[DQH 4 Ionomer of sulphur-containing polyester urethane (PUSI)

5 Polyester urethane (BUTYP T-261)

6 Polyester urethane (BUTYP T-261) /3% coordination compound

7 Polyester urethane (BUTYP T-261) /5% coordination compound

8 Polyester urethane (BUTYP T-261) /3% bis(hydroxyalkyl)polydimethylsiloxane

9 �3RO\HVWHU�XUHWKDQH��%87<3�7����������.�&�GLK\GUR[\PHWK\O� vinyloligoorganosiloxane

10 Polyester urethane (BUTYP T-261) /3% .�&�GLK\GUR[\PHWK\OYLQ\O�ROLJRRUJDQRVLOR[DQH/ 3% coordination compounds

Tribological properties33 of the polymeric matrices and antibiocorrosive coatings

have studied by using a Nanovea pin-on-disk tribometer from Micro Photonics Inc.

The tribometer provides dynamic friction results under rotation conditions34. 440 steel

balls made by Salem Specialty Balls have used with the diameter of 3.2 mm. The tests

have performed under the following conditions: temperature 20±2oC, speed 100 rpm,

radius 2.0 mm, loads 5.0 N. The number of revolutions was 3000.

As it was shown in Figs 4 and 5 dynamic friction for polyurethane matrices

PDLQO\�GHSHQGV�RQ�WKHLU�VWUXFWXUH�DQG�WKH�VWUXFWXUH�RI�PRGL¿HU��%\�WKH�DQDO\VLV�RI�FXUYHV�RI�G\QDPLF� IULFWLRQ�YDULDWLRQ� IRU�QRQ�PRGL¿HU�DQG�PRGL¿HU�SRO\�XU�HWKD�QHV�and antibiocorrosive coatings based on them (Figs 4 and 5) was established that the

YDOXH�RI�G\QDPLF�IULFWLRQ�LV�KLJK�IRU�QRQ�PRGL¿HG�SRO\XUHWKDQH�PDWULFHV�DQG�FRDWLQJV�based on them. The addition of silicon-organic oligomers (3–5 wt. %) to polyurethane

matrices leads to decrease of the mentioned above parameter (Fig. 6).

Fig. 4. Dependence of the dynamic friction on distance of sliding for poly urethane matrices and antibio-

FRUURVLYH�FRDWLQJ�¿OPV�EDVHG�RQ�WKHP��1–5, Table 5)

957

Fig. 5. Dependence of the dynamic friction on distance of sliding for matrix based on poly ester urethane

(BUTYP T-261) and the corresponding anti bio corro sive coatings (5–10��7DEOH�����QRQ�PRGL¿HG�DQG�PRGL¿HG�ZLWK�VLOLFRQ�RUJDQLF�ROLJRPHUV

By doping of bioactive coordination compounds in polyester urethane matrix

based on 4,4-dimethyl methane di iso cyanate and olygobuthylenglycole adipinate the

YDOXH�RI�WKH�FRHI¿FLHQW�RI�G\QDPLF�IULFWLRQ�LV�LQFUHDVHG��7KLV�IDFW�FRXOG�EH�H[SODLQHG�E\�LQÀXHQFH�RI�WKHLU�VSDWLDO�VWUXFWXUH��,W�ZDV�VKRZQ�WKDW�DV�D�UHVXOW�RI�WKH�PRGL¿FD-tion of polyester urethanes by silicon-organic oligomers the dynamical friction was

UHGXFHG��)LJ������ZKLFK�LV�GXH�WR�WKH�KLJK�SOD�VWL�FLVHG�DELOLW\�RI�WKH�ÀH[LEOH�VLOR[DQH�oligomers.

Fig. 6. Comparison of the values of DYHUDJH�dynamic friction for polymer matrices and antibio corrosive

coatings based on them (Table 5)

7KH� REWDLQHG� UHVXOWV�ZHUH� DOVR� FRQ¿UPHG� E\� VWXG\LQJ� RI� VXUIDFH�PRUSKRO-RJ\��VFDQQLQJ�HOHF��WURQ�PLFURVFRS\��RI� WKH�¿OPV�IURP�PRGL¿HG�DQG�QRQ�PRGL¿HG�polymeric matrices purpose for creation of anti biocorrosive coatings (Fig. 7). Plastic

GHIRUPDWLRQ�RI�FRUUHVSRQGLQJ�¿OPV�XQGHU�WKH�FRQVWDQW�ORDG�HTXDO�WR���1�VKRZHG�WKDW�D�VSOLW�EHKDYLRXU�RI�VXOSKXU�FRQWDL�QLQJ�SRO\HVWHU�XUHWKDQH��386���PRGL¿HG�E\�.�&�

958

dihydroxy methyl vinyl oligoorgano siloxane, charac te ri sed with less crack nucleation

LQ�FRP�SD�ULVRQ�ZLWK�QRQ�PRGL¿HU�386��7DEOH�����,W�PXVW�EH�QRWHG�WKDW�SRO\HVWHU�XUH-WKDQH�%87<3�7������PRGL¿HG�E\�ELV��K\GUR[\�DON\O��SRO\GLPHWK\OVLOR[DQH��7DEOH�����demonstated least crack nucleation among the tested polymeric matrices.

Fig. 7��6XUIDFH�PRUSKRORJ\�RI�WKH�SRO\PHULF�¿OPV�IRU�DQWLELRFRUURVLYH�FRDWLQJV�EDVHG�RQ�QRQ�PRGL¿HG�DQG�PRGL¿HG�SRO\�XU�HWKD�QHV��7DEOH����

The hydrophobicity of the obtained antibiocorrosive coatings by gravimetric

method was determined. It was established, that during 300 h the water absorption abil-

LW\�IRU�WKH�PRGL¿HG�PDWULFHV�E\�VLOLFRQ�RUJDQLF�ROLJRPHUV�GRHV�QRW�H[FHHGV�������7KH�LQÀXHQFH�RI�LVRWKHUPDO�DJHLQJ�����DQG���oC), the so-called weather ability

(stability towards O2, CO

2 and moisture complex action) and photochemical stability

(stability towards ultraviolet and visible light) was studied. It was shown that dur-

ing more than 3 months (at room temperature) the initial appearance (state), colour,

optical tran sparency and mechanical properties (surface homo geneity without splits

formation) of antibiocorrosive coatings (Tables 5, 8–10) did not worsen.

By preliminary investigations it was established that the created antibiocorrosive

composites could be used for: prevention of materials from bio-deterioration and non-

controlled biodegradation; inhibition of growth and expansion of micro organisms,

which are causal factors of infectious diseases, for prophylaxis and treatment of the

above-mentioned diseases35.

The created composites can be also recommended for preparation of protective

FRYHUV�ZLWK�PXOWL�YHFWRULDO�DSSOLFDWLRQ��¿OP�PDWHULDOV�DQG�LPSUHJQDWLQJ�FRPSR�VLWLRQV��stable to biocorro sion; materials with antimycotic properties for prophylaxis and treat-

ment of mycosis; bio lo gically active polymer composite materials for protection of

museum exhibits; for human protection during its contact with micro orga nisms36.

959

CONCLUSIONS

1. Quantitative struc ture–properties relationships (QSPR/QSAR) based on experi-

mental data for con struction of models of dependences of physical properties of bio-

logically active 16 nitrogen-con taining compounds with bioactive spatial carbocyclic

(adamantane) groups, synthesised by us, on mole cu lar structures have been studied.

2. Several sets of molecular descriptors have been used. Presence of the dataset

outliers was con t rol led by using PCA; to ascertain the quality of models cross-

validation has been used.

3. Based on the performed research, one concludes that the best models have

been acquired by the use of the GETWAY description of obtained compounds has

been carried out.

4. Virtual bio screening and activity towards various micro organisms of the ob-

tained com pounds have been studied. Area of their application has been established.

0LFUR�ELR�ORJLFDO�VWXG\�RI�WKH�LQYHVWLJDWHG�FRPSRXQGV�FRQ¿UPHG�WKH�HYDOXDWHG�YLUWXDO�concepts.

5. Polyurethanes with various structures as a polymeric matrix for antibiocor-

URVLYH�FRDWLQJV�ZHUH�FKR�VHQ�DQG�XVHG��)RU�PRGL¿FDWLRQ�WKHLU�WULERORJLFDO�SURSHUWLHV�silicon-organic oligo mers have been used. New effective, photochemical stable and

‘short-time’ active inorganic-organic anti bio corro sive coatings have been obtained.

Tribological properties of the obtained polymeric composites and antibiocorrosive

FRDWLQJV�KDYH�EHHQ�GHWHUPLQHG��7KHUH�ZDV�HVWDEOLVKHG�WKDW�WKH�PRGL¿FDWLRQ�SURFHVV�could be used to improve tribological properties of polyurethanes.

ACKNOWLEDGEMENTS

$XWKRUV�WKDQN�µ6KRWD�5XVWDYHOL¶�1DWLRQDO�6FLHQFH�)RXQGDWLRQ�RI�*HRUJLD�IRU�¿QDQ-

cial support and Dr Tea Datashvili for her help to carry out the tribological studies of

antibiocorrosive coatings.

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Received 16 May 2012

Revised 18 August 2012