A.Konovalov NANOASSCIATES ARE THE MATERIAL CARRIES OF THE BIO-EFFECTS MANIFESTED BY HIGH DILUTED WATER SOLUTIONS OF BAC A.Arbuzov Institute of Organic and Physical Chemistry of Kazan Scientific Center of Russian Academy of Sciences, WATER CONFERENCE 2013 BULGARIA

DEDICATED TO TWENTY FIVE ANNIVERSARY OF PUBLICATION J.BENVENISTE ARTICLE IN NATURE (1988)

3 Факты, не объяснимые существующими теориями, наиболее дороги для науки, от их разработки следует по преимуществу ожидать её развития в ближайшем будущем. А.М.Бутлеров, 1879 г. Facts that are not explained by existing theories are the most valuable for science as far as exactly from their study we should expect its further development in the near future. A.Butlerov, 1879

4 Facts that are not explained by existing theories are the most valuable for science as far as exactly from their study we should expect its further development in the near future. A.Butlerov, 1879

MANIFESTATION OF BIOLOGICAL ACTIVITY (BIOEFFECTS) BY HIGH DILUTED WATER SOLUTIONS (HDWS) MAY BE CONSIDERED AS SUCH FACTS THERE ARE THOUSANDS EXAMPLES OF THIS PHENOMENON AND THEY ARE KNOWN MORE THAN HUNDRED YEARS BUT FOR RECENTLY TIME THERE WAS NOT SATISFACTORY EXPLANATION OF SUCH FACTS WE GUESS THAT MATERIAL CARRIES OF THIS PHENOMENON ARE NANOASSOCIATES

666 Formation of the Nano-sized Moleculare Ensambles in High Diluted Aqueous Solutions. Effect of Ultra-low Concentrations and Electromagnetic Fields. A.I.Konovalov October 18-21, 2012, West Dover, Vermont, USA The VII th Annual Conference on The Physics, Chemistry and Biology of Water» A.E.Arbuzov Institute of Organic and Physical Chemistry of RAS, Kazan

FORMATION OF NANOASSOCIATES IS THE KEY TO THE UNDERSTSNDING OF THE BEHAVIOR OF HIGH DILUTED AQUEOUS SOLUTIONS

Beginning of investigations 2006 First oral communication 2007 First publications on DLS and physicochemical study Using of term of «NANOASSOCIATES» 2009 First pulication on the influence of electromagnetic fields 2011 CHRONICLE OF OUR WORK

NANOASSOCIATES are nanosized (up to 400 nm) molecular ensembles, which are formed in high diluted water solutions (HDWS) of BAC under influence of two effectors: solutes and external (natural) electromagnetic fields – and consist of water molecules mainly (up to 500 millions). Formation of nanoassociates designate both physicochemical and ( it is very important) biological properties of HDWS

ALMOST HUNDRED COMPOUNDS WERE STUDIED BY SEVERAL METHODS IN – M CONCENTRATION INTERVAL

ANTIOXIDANTS PLANT GROWTH REGULATORS NEUROMEDIATORS VITAMINS HORMONES ANTICEPTICS ANXIOLITICS COMPOUNDS WITH KNOWN AND UNKNOWN BIOLOGICAL PROPERTIES

12 Phenozan potassium salt DLS STUDY

Phenozan potassium salt ζ – potencial, mV

MELAFEN

15 χ, µS/cm «non-classic behavior»

CORRELATIONS BETWEEN PARAMETRS OF NANOOBJECTS AND PHYSICOCHEMICAL PROPERTIES OF HDWS EXIST D, ζ χ, σ … NANOOBJECTS SOLUTIONS

PHENOZAN POTASSIUM SALT : ζ-potencial of nanoassociates and electrical conductivity of solutions

18 ICHFAN C-10: ζ potencial of nanoassociates and electrical conductivity of solutions R=СH 2 CH 2 N +( CH 3 ) 2 C 10 H 21 Br - VIP-1

NANOASSOCIATES сreate «THE WEATHER» IN HDWS

NO SOLUTES NO NANOASSOCIATES SOLUTES ARE EFFECTORS OF NANOASSOCIATES FORMATION BUT NOT ONLY IT NEEDS EM FIELDS ALSO

21 1-Laboratory table 2-Permalloy container PHENOZAN POTASSIUM SALT NO NANOASSOCIATES magnetic induction (В) of geomagnetic field in Kazan is 53· 10 3 nTl, in container nТl VIP-2

22 NO EM FIELDS NO NANOASSOCIATES ! Transformation of «non-classic behavior» into «classic behavior» of solutions NO SOLUTES NO NANOASSOCIATES

23 ~ 25% SOLUTES DO NOT FORM NANOASSOCIATES NOT ALL SOLUTES FORM NANOASSOCIATES

24 CMC = 7 ·10 -5 M AMPHIPHILIC PHOSPHACUMARINE (APC) «classic behavior» NO NANOASSOCIATES

25 1-Laboratory table 2-Permalloy container PHENOZAN POTASSIUM SALT NO NANOASSOCIATES t.c

26 NO EM FIELDS NO NANOASSOCIATES NO BIOEFFECTS ?

The concentration dependence in the membrane lipid microviscosity of synaptosome using HDWS of PhK, фиксируемой методом ЭПР с помощью стабильного свободного радикала 16-доксилстеариновой кислоты, нитроксильный фрагмент которой локализован на глубине Αо, 1-Laboratory table 2-Permalloy container Maltseva E., Kasparov V., Palmina N. VIP-3

28 COMPARISON OF PHYSICOCHEMICAL AND BIOLGICAL PROPERTIES OF HDWS OBTAINED IN INDEPENDENT EXPERIMENTS

29 PHENOZAN POTASSIUM t.c

30 PHENOZAN POTASSIUM

31 NO EM FIELDS NO NANOASSOCIATES NO BIOEFFECTS !

32 NANOASSOCIATES ARE MATERIAL CARRIES OF HDWS BIOEFFECTS !

The concentration dependence of change in the membrane lipid microviscosity of synaptosome using DSWS of PhK, фиксируемой методом ЭПР с помощью стабильного свободного радикала 16-доксилстеариновой кислоты, нитроксильный фрагмент которой локализован на глубине Αо, 1-Laboratory table 2-Permalloy container Maltseva E., Kasparov V., Palmina N.

MORE DEEP INVESTIGATION OF HDWS BIOLOGICAL ACTIVITY IN CONNECTION WITH NANOASSOCIATES FORMATION

N.M.Emanuel Institute of Biochemical Physics of RAS N.Palmina team I.Zhigacheva team

Changing of sign of bio-effects of BAC by dilution of solutions under influence of nanoassociates formation

GUANIBIPHOS

_ + GUANIBIPHOS: THE INFLUENCE ON THE DEVELOPMENT OF MICROORGANISMS t.c

ACETYLHYDRAZIDE OF TIACALIX[4]ARENE: INFLUENCE ON THE GROWTH P.BACILLUS SPP - Bacillis subtillis Bacillis subtillis L 2 t.c

ACETYLHYDRAZIDE OF TIACALIX[4]ARENE: INFLUENCE ON THE CONSUPTION OF OXYGEN BY CUTTED OFF ROOTS OF WHEAT t.c

DERIVATIVE OF CALIX[4]RESORCINE

Концентрационная зависимость биоэффекта, в качестве которого взято потребление кислорода отсеченными корнями пшеницы к 5-му часу инкубации в растворе КРА по отношению к контролю (раствор, не содержащий КРА). + _ + DERIVATIVE OF CALIX[4]RESORCINE: INFLUENCE ON THE CONSUPTION OF OXYGEN BY CUTTED OFF ROOTS OF WHEAT t.c

++ _

45 « At present it is evident that remidies can be active in ultra-low doses and these effects in their trends can differ from effects by therapevtic doses.» М.: ФИЗМАТЛИТ, с.

46 Влияние бруфена в широком диапазоне концентраций на высвобождение [ 3 H]-метаболитов арахидоновой кислоты перитониальными макрофагами мыши. За 100 % - отсутствие бруфена IBUPROPHENE – FEBRIFUGE – М – стимулирующее воздействие – М - не влияет – М – ингибирующее воздействие Шимановский Н.Л., Епинетов М.А., Мельников М.Я. Молекулярная и нанофармакология. - М.: ФИЗМАТЛИТ, с.

47

THE NECESSITY OF THE STUDY OF ALL REMIDIES IN WIDE INTERVAL OF CONCENTRATIONS INCLUDING HDWS

The concentration dependence in the membrane lipid microviscosity of synaptosome using DSWS of PhK, фиксируемой методом ЭПР с помощью стабильного свободного радикала 16-доксилстеариновой кислоты, нитроксильный фрагмент которой локализован на глубине Αо, 1-Laboratory table 2-Permalloy container Maltseva E., Kasparov V., Palmina N.

The concentration dependence of the changes in D of nanoassociates (1) and in the membrane lipid microviscosity of synaptosome (2) using HDWS of PhK in hypoelectromagnetic conditions t.c

CONCENTRATION DEPENDENCE OF SIZE DISTRIBUTION IN SOLUTIONS OF CDAzF S. Samal, K. E. Geckeler // Chem. Commun. – – P M. Sedla´k // J. Phys. Chem. B. – – No – P M. Sedla´k // /J. Phys. Chem. B. – – No – P M. Sedla´k // J. Phys. Chem. B. – – No – P L.O. Kononov, N.N. Malysheva, A.V. Orlova // Eur. J. Org. Chem. – – P. 1926–1934

M. Sedla´k // J. Phys. Chem. B. – – No – P Typical example of bimodal dynamic light scattering from solutions of low molar mass compounds and mixtures of liquids. Data were obtained on a 4.1 mass % aqueous solution of D-glucose.

SCHEMATIC IMAGES OF POSSIBLE DOMAINS STRUCTURES M. Sedla´k // J. Phys. Chem. B. – No.110. – P Supramolecular domains

KONONOV L.O. (N.Zelinsky Institute of Organic Chemistry, RAS) SUPRAMERS 2012 SUPRAMER ISOMERY REGULATION OF RATES AND STEREOSELECTIVITY OF GLYCOSITION REACTIONS BY MIXTURES OF SOLVENTS AND REAGENTS, WHICH CORRESPOND TO DEFINITE SUPRAMERS

SIZE DISTRIBUTION OF NANOOBJECTS BY DILUTION GUANIBIPHOS M% pH 3,5 6,8 4,6 5,7

Classical molecular aggregates Nanoassociates Supramolecular domains lg C (C моль/л)

SOME NANOASSOCIATES PROBLEMS WHAT ARE THE NATURE OF NANOASSOCIATES? WHAT ARE THE FORCES WICH CONNECT MILLIONS MOLECULES? HOW NANOASSOCIATES INTERACT WITH BIO-OBJECTS? ARE THERE NANOASSOCIATES IN BIO-OBJECTS? IF THERE ARE, WHAT IS THEIR ROLE? MAY BE THIS IS ONE OF CANALS OF INFLUENCE OF EXTERNAL EMF ON LIVING SYSTEMS?

SOME NANOASSOCIATES PROBLEMS WHAT ARE THE NATURE OF NANOASSOCIATES? WHAT ARE THE FORCES WICH CONNECT MILLIONS MOLECULES? HOW NANOASSOCIATES INTERACT WITH BIO-OBJECTS? ARE THERE NANOASSOCIATES IN BIO-OBJECTS? IF THERE ARE, WHAT IS THEIR ROLE? MAY BE THIS IS ONE OF CANALS OF THE INFLUENCE OF EXTERNAL EMF ON LIVING SYSTEMS?

AND WHAT ABOUT MEMORY OF WATER? DOES IT EXISTE OR DOES NOT? IS THERE SOME MATERIAL IMIGE OF SOLUTE IN WATER WICH IS CONCERVED AND TRANSLATED BY DILUTION WITHOUT CHANGING? THE ANSWER ON SUCH QUESTION IS NO INFORMATION ABOUT SOLUTE (IN WICH FORM –IT IS UNKNOW EXACTLY MEANWHILE) EXISTES, BUT IT IS TRANSFORMED BY DILUTION UP TO OPPOSITE NANOASSCIATES ARE REFLECTION OF SUCH TRANSFORMATION

laboratory table permalloy container Water/ DMSO (30%) Water/ DMF (30%) С 2 H 5 O H/water (40%)|

NANOOBJECTS IN VODKA AND COGNAC 40% С 2 Н 5 ОН in WATER VODKA «OLD KAZAN» RUSSIAN COGNAC «FIVE STARS» A.I.Konovalov I.S.Antipin I.I.Stoykov 2008

ALL INVISTIGATIONS OF WATER AND WATER –ORGANIC SOLUTIONS SHOULD BE MADE WITH USING DLS METHOD

Dr.Sci. Ryzhkina I.S. Ph.D. Murtazina L.I. Ph.D. Kiseleva Ju.V. Fattakhov S. G. Solov´yeva S. E. Mironov V.F. Timosheva A.P. Kadirov M.K. Safiullin R.A. Litvinov A.I. Maltseva E. Kasparov V. Palmina N.P. Zhigacheva I.V. Valitova Ju.N. Fridland S. V. A.E. Arbuzov Institute of Organic and Physical Chemistry of Kazan Scientific Centre of Russian Academy of Sciences Acknowledgments N.M.Emanuel Institute of Biochemical Physics of RAS Kazan Institute of Biochemistry and Biophysics of RAS Kazan NationalTechnological University A.E. Arbuzov Institute of Organic and Physical Chemistry of Kazan Scientific Centre of RAS

All our articles (full texts, English versions) are in my computer. Our self-review will be published in Russ.Chem.Bull., Int.Ed., 2014, 1.

Model of the hydrated C 60 fullerene (C 60 HyFn = stable donor-acceptor complex of C 60. {H 2 O} n) surrounded by long-range shells of ordered water Andrievsky G.V., V.I. Bruskov, A.A. Tykhomyrov, S.V. Gudkov // Free Radical Biology & Medicine. – – V. 47. – P

DERIVATIVE OF CALIX[4]RESORCINE

АСМ изображение поверхности образца после снятия иглой кантеливера с подложки (с=10 -7 М) М М М М М М а б в г д е

S.Y. Lo, X. Geng, D. Gann // Physics Letters A. – – V – Р Residues from evaporated 1.7 × 10 7 M NaCl solution taken with AFM and with EFM

DERIVATIVE OF CALIX[4]RESORCINE KAZAN FEDERAL UNIVERSITY INSTITUTE OF SOLUTION CHEMISTRY, RAS (IVANOVO)

MELAFEN

A.Arbuzov Institute (Kazan) S.Fattachov, 1993

Спектры флуоресценции продуктов ПОЛ в мембранах митохондрий проростков гороха в условиях действия недостаточного увлажнения с умеренным охлаждением и обработки семян гороха мелафеном Е.М. Миль, В.И. Бинюков, И.В. Жигачева, С.Г. Фаттахов, академик А.И. Коновалов / ИЗУЧЕНИЕ ВЛИЯНИЯ МЕЛАФЕНА НА МИТОХОНДРИИ ПРОРОСТКОВ ГОРОХА ПРИ СТРЕССОВЫХ ВОЗДЕЙСТВИЯХ МЕТОДОМ АСМ А) В) B) C)C) АСМ изображение митохондрий из проростков гороха в контроле (А), при воздействии «холод-засуха» (В) и в присутствии мелафена- «холод-засуха» (С) Площадь (мкм х мкм) Ср. значение контроль 2,31,53,1 Холод-засуха3,62,34,9 Мел-холод- засух1,71,12,3 Средняя высота (нм) Ср. значение контроль 82,368,196,4 Холод-засуха101,590,5112,6 Мел-холод- засух7564,385,6 MELAPHEN ( M): THE INFLUENCE ON MITOCHONDRIAL MORPHOLOGY AND POL 0F 5-DAY OLD SEEDINGS OF PEA IN STRESS CONDITION